DeBakey Awards

Cullen Foundation Endowed Chair and Director,
CIBR Center for Computational and Integrative Biomedical Research
Professor of Molecular and Human Genetics, and 
Biochemistry and Molecular Pharmacology

Dr. Lichtarge’s research combines computer analyses with experiments to understand the molecular evolution of genes and pathways — how their functions may be altered by genetic mistakes or how they may be re-engineered to new designs. Using this innovative approach, he has identified genes and molecular pathways linked to autism, cancer and Alzheimer’s disease.  

Dr. Lichtarge uses a mathematical equation that quantifies the evolutionary action of mutations on fitness to bridge molecular biology and population genetics. In his studies on autism spectrum disorders (ASD), this approach revealed characteristic differences in genes and processes linked to nerve transmission and neurodevelopment, shedding light on the molecular mechanisms of ASD. A key result was that the predicted fitness impact of variants correlated with the IQ of individuals with the conditions.  

His work in cancer identified 460 genes undergoing selection in tumors. Some, not previously known, were then validated experimentally, providing an improved understanding in cancer biology. In his study of Alzheimer’s disease, he combines evolutionary calculations with machine learning. This approach uncovered immune response genes and showed that analyses of ever smaller patient cohorts still could robustly identify relevant genes.

Collectively, Dr. Lichtarge’s studies establish this new calculus of evolutionary fitness as a fundamental tool to discover disease mechanisms and inform precision medicine. His work unifies elementary concepts from mathematics, physics and evolution into a single, coherent and powerfully predictive model of life.

Professor
Department of Molecular and Human Genetics

Dr. Nakada’s research focuses on the molecular and cellular mechanisms that regulate the biology of hematopoietic stem cells (HSCs) (the parent cells of blood cells) and leukemia, cancers of blood-forming cells. He’s particularly interested in understanding how HSCs are maintained throughout life, the mechanisms that transform normal HSC into cells that give rise to acute myeloid leukemia (AML) and identifying vulnerabilities in these cancerous cells to improve AML treatment.

Regarding the biology of HSC, his lab discovered that the female sex hormone estrogen promotes the proliferation of HSCs, providing a novel conceptual framework to investigate blood disorders that have sex differences, such as blood cancers and autoimmune diseases.

Dr. Nakada’s work also established that AML cells highjack some of the cells’ metabolic pathways, turning these pathways into vulnerabilities that could guide the development of novel therapies. For example, Dr. Nakada found that while healthy HSCs do not depend on the metabolic pathway AMPK, the pathway is critical for AML cells, suggesting that therapies directed at AMPK could help control AML.

Nakada also showed that AML cells depend on selenium, a chemical element that is essential for cells in trace amounts, and that this dependency can be targeted by restricting selenium in the diet.  

These studies were facilitated by Dr. Nakada’s development of an efficient method to edit the genomes of HSCs. This method was used to develop new mouse models of hematological malignancies and to investigate the genetic interactions in both mouse and human AML models, setting the research conducted by the Nakada lab at the forefront of HSC leukemia stem cell biology. 

Human Genome Sequencing Center and Department of Molecular and Human Genetics

Dr. Rogers is an internationally recognized expert in the genetics and genomics of nonhuman primates. One area of his research focuses on the discovery and characterization of genetic variation within nonhuman primate species that are used as models of human disease. These efforts have identified several novel and significant spontaneous genetic models of human clinical disorders, including retinal disease, endometriosis, colorectal cancer and anxiety disorders. His second line of research is the development of new fundamental information regarding primate genomics, including but not limited to production of whole genome reference assemblies, quantitative analysis of genetic diversity within and among wild populations of nonhuman primates, the analysis of inter-species hybridization and studies of mechanisms of primate speciation.

Rogers serves as one of three co-leaders of the Primate Conservation and Sequencing Consortium, an international collaboration involving primatologists, geneticists, bioinformaticians and evolutionary biologists. He and his co-leaders supervised the whole genome sequencing of nonhuman primates from 233 distinct species, the largest dataset of primate genomic information published to date. The data revealed new insights into primate evolution, biodiversity conservation and genetic causes of human disease, and the findings were published in a series of five articles in a special issue of Science this year.

Assistant Professor of Neuroscience and Biochemistry and Molecular Biology
McNair Scholar

Dr. St-Pierre's lab develops new tools and methods to accelerate neuroscience research. He does this through the engineering of fluorescent indicators of neural activity, optogenetic tools to silence neurons, synthetic gene circuits, and novel methods for high-throughput screening.  

Three recent publications show the depth and breadth of his research program and how he works in a novel and creative way to overcome difficulties in advancing neuroscience research.

His paper on synthetic neurobiology in Nature Communications shows how Dr. St-Pierre is overcoming a major challenge in heterologous expression studies in that different cells will be transfected/transduced with varying numbers of plasmids/vector particles, resulting in overexpression and underexpression of the protein of interest. To remedy this problem, he and his team have engineered and published a transcriptional circuit — called the Equalizer — that buffers this variation in copy number. They are now further developing their Equalizer system for the controlled expression of indicators and actuators in vivo.

The second paper in Science Advances on accelerating protein engineering addresses a major problem that Dr. St-Pierre overcame to perform high throughput screening of novel genetically encoded indicator and reporter proteins. Genetic indicator development remains long and tedious given the limited size of libraries that can be screened with current technologies. To accelerate engineering, Dr. St-Pierre’s group has developed and published a novel optical platform (SPOTlight) that can screen up to a million variations per round, several orders of magnitude larger than current libraries. They are applying this platform to various projects in the lab while continuously improving the underlying technology.

Finally, in Cell, Dr. St-Pierre describes the development and employment of a revolutionary genetically encoded voltage-sensor that works optimally under two-photon (2P) illumination to track neuronal voltage changes in neuron and other cells in vivo. Transmembrane voltage is a critical information carrier in the brain: neurons communicate and process information by regulating their membrane voltage, and aberrant neuronal voltage dynamics are implicated in many neurological disorders. Tools to record voltage signals are thus fundamental to studying how the brain functions in health and disease. Dr. St-Pierre’s lab focuses on evolving Genetically Encoded Voltage Indicators (GEVIs) —fluorescent proteins whose brightness is modulated by voltage — as they promise to detect voltage dynamics in specific cell types over long time scales, deep in the brain, and with millisecond timescale and micron-scale spatial resolution. They show in this paper that their recently developed voltage indicator enables sustained (>30 min), deep (layer 5) optical recording of fast (<1 ms) voltage dynamics in awake behaving mice.

Associate Professor at the Human Genome Sequencing Center, Baylor College of Medicine 
Associate Professor at the Department of Molecular and Human Genetics, Baylor College of Medicine 
Adjunct Associate Professor at the Department of Computer Science, Rice University

Dr. Sedlazeck’s research focuses on the understanding of genome instability and complex variations and their impact on evolution and disease. His team spearheaded the detection of Structural Variations using long read sequencing data. This research has significantly advanced the understanding of complex cardiovascular, neurological and Mendelian diseases, uncovering crucial insights into their underlying genetic mechanisms and potential avenues for diagnosis and treatment. He remains at the forefront of research on clinically significant genes within complex regions of the human genome, often referred to as 'dark' regions.  

He played an instrumental role in the completion of sequencing the remaining sections of the human genome, with his groundbreaking findings published in Science last year. He has made significant contributions to clinical diagnostics by collaborating with Stanford Clinic and Google Health to improve the accuracy of clinical sequencing and reduce the time it takes from weeks to just eight hours.

For the past five years, he has organized an annual hackathon where people from around the world meet and work together on computational prototypes to obtain deeper insights into open genomics and biomedical research questions. This event brings together a diverse group of approximately 90 individuals each year from all continents, including students and faculty members, fostering a collaborative spirit that enriches the field of computational biology. Sedlazeck also is an adjunct associate professor of computer science at Rice University.

Professor, Associate Director for Basic Sciences
USDA/ARS Children's Nutrition Research Center, Department of Pediatrics
Section of Endocrinology, Diabetes, and Metabolism, Department of Medicine
Department of Molecular and Cellular Biology
Baylor College of Medicine

Dr. Yong Xu’s research program focuses on central mechanisms for the regulations of feeding behavior and body weight. Using cutting-edge modern neuroscience technology, Dr. Xu has identified novel hypothalamic circuits, neural messengers and intracellular molecules critical for the regulation of feeding behavior and body weight. His discoveries are highly relevant to common human diseases, especially obesity, diabetes and eating disorders.

Recently, Dr. Xu and his collaborators identified a novel mechanism for human obesity that will guide better diagnosis and treatment for a subset of individuals with obesity. Many genetic variants in humans that affect weight are enriched in the brain, implicating neural dysfunctions in the susceptibility to obesity. Dr. Xu teamed up with physician-scientists to combine human genetics and basic animal neuroendocrinology by using the human/mouse genetic approach to identify HTR2C (encoding serotonin 2C receptor) mutations as the cause of human obesity. These findings indicate that the HTR2C gene should be included in the genetic screening panel for human obesity. In addition, Dr. Xu revealed that the impaired melanocortin signaling in the brain contributes to overeating and weight gain caused by the HTR2C mutations, and therefore suggest that patients with HTR2C deficiency can be treated by an FDA-approved melanocortin agonist (IMCIVREE, also known as setmelanotide).

Dr. Xu has also revealed a potential pathophysiologic basis for anorexia nervosa and provided a mechanistic framework for developing novel therapeutic strategies for this disease. Dr. Xu showed that dopamine (DA) neurons bidirectionally regulate the activity of midbrain 5-HT neurons, with weaker stimulation causing dopamine receptor D2 (DRD2)-dependent inhibition and overeating, and stronger stimulation causing dopamine receptor D1 (DRD1)-dependent activation and anorexia. In a mouse model for anorexia nervosa, DA actions on 5-HT neurons shift from a DRD2-mediated neurotransmission to a DRD1-mediated process, which causes constant activation of 5-HT neurons, resulting in anorexia. These results revealed an interesting DA to 5-HT neurocircuit whose neurotransmission and behavioral outcome are bidirectional, depending on the strength of DA inputs. The findings indicate that an enhanced DRD2 neurotransmission onto 5-HT neurons contributes to development of anorexia nervosa, and further demonstrate the therapeutic potential of DRD1 antagonists in this devastating and life-threatening disease.

In addition, Dr. Xu identified a novel exercise-induced metabolite that reduces food intake and improves glucose balance, which paved the way to develop exercise mimetics as effective anti-obesity and anti-diabetic medicines. Dr. Xu and the team showed that exercise stimulates production of Lac-Phe, a blood-borne signaling metabolite. In diet-induced obese mice, Lac-Phe reduces food intake without affecting movement or energy expenditure. Chronic treatment with Lac-Phe decreases adiposity and body weight and improves glucose homeostasis. Conversely, genetic ablation of Lac-Phe biosynthesis in mice increases their food intake and leads to obesity. These data define a conserved exercise-inducible metabolite that controls food intake and influences systemic energy balance, and resulted in a patent (“Lactoyl amino acids for the treatment of metabolic disease”).

Associate Dean of the National School for Tropical Medicine at Baylor College of Medicine
Co-Director of the Texas Children's Hospital Center for Vaccine Development

Dr. Bottazzi is an internationally recognized tropical and emerging disease vaccinologist, global health advocate and co-creator of a patent-free, open science COVID-19 vaccine technology that led to the development of Corbevax, a COVID-19 vaccine for the world. She pioneers and leads the advancement of a robust infectious and tropical disease vaccine portfolio tackling diseases such as coronavirus, hookworm, schistosomiasis and Chagas that disproportionally affect the world’s poorest populations. She also has established innovative partnerships in Latin America, the Middle East and Southeast Asia, making significant contributions to innovative educational and research programs, catalyzing policies and disseminating science information to reach a diverse set of audiences.

As global thought-leader she has received national and international highly regarded awards, has more than 280 scientific papers and participated in more than 250 conferences worldwide. She is a member of the National Academy of Science of Honduras and an Emerging Leader in Health and Medicine of the National Academy of Medicine in the U.S.

Bottazzi is a fellow of the American Society of Tropical Medicine and Hygiene (ASTMH), the Executive Leadership in Academic Medicine (ELAM) and the Leshner Leadership Institute for Public Engagement and senior fellow of the American Leadership Forum (ALF). Forbes LATAM in 2020 and 2021 selected Bottazzi as one of 100 Most Powerful Women in Central America. Bottazzi has served in several national academies ad-hoc committees and serves as co-chair of the Vaccines and Therapeutics Taskforce of the Lancet Commission on COVID-19. In 2022, alongside Dr. Peter Hotez, she was nominated by Congresswoman Lizzie Fletcher of Texas for the Nobel Peace Prize.

Dean of the National School of Tropical Medicine at Baylor College of Medicine
Co-Director of the Texas Children’s Hospital Center for Vaccine Development

Dr. Hotez is an internationally recognized physician-scientist in neglected tropical diseases and vaccine development.  As co-director of the Texas Children’s Center for Vaccine Development, he leads a team and product development partnership for developing new vaccines for hookworm infection, schistosomiasis, leishmaniasis, Chagas disease and SARS/MERS/SARS-2 coronavirus, diseases affecting hundreds of millions of children and adults worldwide, while championing access to vaccines globally and in the U.S.  

In December 2021, Hotez led efforts at the Texas Children’s Center for Vaccine Development to develop a low-cost recombinant protein COVID vaccine for global health, resulting in emergency use authorization in India. In 2022 Hotez and his colleague Dr. Maria Elena Bottazzi were nominated for the Nobel Peace Prize for “their work to develop and distribute a low-cost COVID-19 vaccine to people of the world without patent limitation.”

In 2014-16, he served in the Obama Administration as U.S. Envoy, focusing on vaccine diplomacy initiatives between the U.S. government and countries in the Middle East and North Africa.  In 2018, he was appointed by the U.S. State Department to serve on the Board of Governors for the U.S.-Israel Binational Science Foundation, and he is frequently called on frequently to testify before U.S. Congress. He has served on infectious disease task forces for two consecutive Texas governors.  For these efforts in 2017 he was named by FORTUNE Magazine as one of the 34 most influential people in healthcare, while in 2018 he received the Sustained Leadership Award from Research!America.

Most recently as both a vaccine scientist and autism parent, he has led national efforts to defend vaccines and to serve as an ardent champion of vaccines going up against a growing national “antivax” threat. In 2019, he received the Award for Leadership in Advocacy for Vaccines from the American Society of Tropical Medicine and Hygiene.  In 2021 he was recognized by scientific leadership awards from the Association of American Medical Colleges and the American Medical Association, in addition to being recognized by the Anti-Defamation League with its annual Popkin Award for combating antisemitism.

Assistant Professor of the Department of Molecular Virology and Microbiology
Member of the Alkek Center for Metagenomics and Microbiome Research

Dr. Joseph Hyser’s research work is dedicated to improving our understanding of host-pathogen interactions. He has focused on characterizing host signaling pathways that enteric viruses, such as rotavirus, destabilize to cause gastrointestinal disease. His work stands out because it is shifting prevailing paradigms within the field.

In recent work, Hyser used calcium biosensor cell lines and organoids he developed to perform long-term live calcium imaging throughout rotavirus infections. This work is paradigm shifting because it firmly established that rotavirus increase calcium through hundreds of discrete calcium signaling events rather than a general, monophasic increase in cytosolic calcium levels. This study also led to the discovery of multiple distinct types of calcium signals present at different stages of the infection.
Another study showed that calcium-conducting viroporins are a broadly conserved strategy used by viruses to exploit host calcium signaling pathways. This finding has opened the door to identify commonly exploited host pathways for which host-targeted antiviral drugs could be developed.

Recently, Hyser published the first direct evidence that viruses can trigger aberrant calcium signaling in uninfected cells by exploiting a host paracrine signaling pathway. Live imaging data show calcium signals coming from rotavirus-infected cells and spreading to surrounding uninfected cells—a type of signal called intercellular calcium waves. He found that eliminating the calcium waves severely reduced rotavirus replication, suggesting that rotavirus has evolved to co-opt this host intercellular signal to increase its replication. Taken together, Hyser’s work establishes a new mechanism by which viruses commandeer nearby uninfected cells to contribute to pathogenesis through paracrine signaling.

Associate Professor of the Department of Pediatrics – Division of Infectious Diseases
Member of the Dan L Duncan Comprehensive Cancer Center and Center for Cell and Gene Therapy

Dr. King’s research focuses on the effects of infection and inflammation on primitive hematopoiesis. As a pediatric infectious diseases physician at Texas Children’s Hospital, King recognized the need to understand bone marrow suppressive effects of chronic infection, and she led the field to characterize hematopoietic stem cell responses in the context of animal models of infection. Her review on the topic of inflammatory modulation of hematopoietic stem cells altered the way the field views the interactions between systemic inflammation and stem cells, with continuing repercussions in the fields of malignant and nonmalignant hematology, aging and immunology.

Using a multidisciplinary approach, she has pioneered the concept that hematopoietic stem cells are extremely sensitive to inflammatory signals in the bone marrow environment. Her research has defined a role for inflammatory signaling in bone marrow suppression following chronic infection and in the emergence of clonal hematopoiesis, a recently defined phenomenon that drives cancer risk and cardiovascular disease in advanced age.

Over the past three years, her research efforts have resulted in 9 senior-author research articles in leading journals in her field including Cell Stem Cell, Cell Reports, and eLife. King’s highly innovative and impactful work at the intersection of immunology and hematology has made her an international leader in the field of stem cell biology. She is a skilled clinician, a healthcare advocate, scientist, administrative leader and trusted mentor.

Dr. Irina Larina’s lab is dedicated to the development of new biophotonic technologies to define pathways involved in live embryo progression and, specifically, cardiac development. She also applies her new biophotonic methods to image developmental processes in various mouse models to elucidate pathophysiological mechanisms underlying reproductive disorders. Larina also develops data processing methods that enable her to uncover new information about congenital defects and reproductive disorders that reveal the dynamics of developmental processes, which have not been accessible before.

Most recently she used second harmonic generation microscopy to image collage fibers in embryonic hearts, revealing a link between structural collagen and regional contractility that suggested a regulatory role for cardiomyocyte contractility in establishing mechanical homeostasis in the developing heart. These findings revealed new features of the biochemical alterations found in congenital heart defects and heart failure. In addition, her lab recently established a method to study the interactions between genetic and mechanical factors in both normal and pathogenic cardiogenesis in vivo, such as arrhythmias.

In the area of reproduction, Larina’s innovative biophotonics technology provided direct visualization of the movement of oocytes and embryos in the fallopian tube. Identifying abnormalities in this process is critical for defining defects in mammalian fertilization and embryogenesis. Using her new approach, which combines optical coherence tomography with intravital imaging, Larina showed that cilia do not drive directional oocyte/embryo transport. The timing of the oocyte/embryo transport is primarily regulated by smooth muscle dynamics at different locations within the oviduct.

Jimmy and Roberta Howell Professor of Cardiovascular Surgery
Vice Chair for Research in the Michael E. DeBakey Department of Surgery
Director of Research in the Division of Cardiothoracic Surgery
Professor in the Department of Molecular Physiology and Biophysics

Dr. LeMaire’s primary clinical interest focuses on the management of patients with thoracic aortic disease, with a particular emphasis on treatment of aortic dissection and thoracoabdominal aortic aneurysms. His corresponding research program focuses on organ protection during aortic surgery, genetic aspects of thoracic aortic disease and molecular mechanisms of aortic degeneration.

He has received funding from the National Institutes of Health, the American Heart Association, the Thoracic Surgery Foundation and the Marfan Foundation for his research studying the pathobiology of thoracic aortic aneurysms and aortic dissection. LeMaire is a past-president of the Association for Academic Surgery and is the current editor-in-chief of the Journal of Surgical Research.

LeMaire also serves as a physician associate in the Department of Cardiovascular Surgery at the Texas Heart Institute and Baylor St. Luke’s Medical Center.

Dr. Shen’s research focuses on understanding the development of vascular diseases. She became the director of the Aortic Disease Research Laboratory in 2008, and has since focused on aortic aneurysms and dissections, highly lethal but poorly understood diseases. She has worked closely with collaborator Dr. Scott LeMaire and together, they have built a translational research program and developed several research directions to investigate the mechanisms of aortic injury, repair and remodeling. The ultimate goal of her research is to develop pharmacological treatments to prevent progressive aortic destruction, maladaptive remodeling and disease deterioration. 

Dr. Sundeep Keswani’s lab, the Laboratory for Regenerative Tissue Repair, is focused on understanding  the molecular mechanism that underlies the fetus’ ability to regeneratively heal cutaneous wounds, as well as the development of novel therapies to achieve scarless wound healing in postnatal tissues, specifically the interaction of inflammation and extracellular matrix to drive fibrotic responses within human skin in response to injury. Most recently he has shown that bacteriophage trigger antiviral immunity and prevent clearance of bacterial infection and that Interleukin-10 producing T lymphocytes (TR1 cells) reduce dermal scarring. In addition to his work in skin, his group also has discovered that hyaluronan attenuates tubulointerstitial scarring in kidney injury. During the last three years, he has published his research outcomes in highly prestigious journals such as Science, Annals of Surgery and JCI Insight.

Keswani also serves as a governor of the American College of Surgeons and continually publishes articles that examine the state of research and surgery, keeping surgeon-scientists highly relevant nationally.

Professor, Dr. Russell J. and Marian K. Blattner Chair Center for Cell and Gene Therapy, Department of Neurosurgery

Dr. Ben Deneen’s lab focuses on developmental gliogenesis, glial control of brain circuit function, and the application of these processes to glial-based diseases of the central nervous system, including malignant glioma and white matter disorders. His work is helping to explain the distinct functions of glial cells in different brain regions, and the myriad roles of these critical cells in normal and aberrant brain function.

Most recently his research has focused on the function of glial cells in the context of cancer, brain function, and in injury. He has shown how brain tumors rewire neural circuits leading to brain hyperactivity, which in turn promotes malignant progression. This work uncovered previously unknown crosstalk between brain tumors and normal neural tissue, suggesting new therapeutic approaches.

Additional work showed that a type of glial cell called an astrocyte has selective functions in different brain regions, and that a specialized subset of these astrocytes affects learning and memory. His lab also showed that astrocytes in different brain regions have distinct responses to injury.

Over the past three years, his research efforts in these areas have produced twelve senior author research articles in high-impact journals including Nature, Neuron, Journal of Clinical Investigation, Cancer Discovery and Nature Neuroscience, among others.

Professor, Molecular Virology, Microbiology and Medicine

Since 2016, Dr. Hana El Sahly has served as principal investigator at Baylor’s National Institutes of Health-funded Vaccine and Treatment Evaluation Unit, where she and her team conduct translational research of vaccine candidates, including vaccines for influenza, neglected tropical diseases and agents that could be used as bioweapons. She is an international leader in translational research of vaccines and her leadership and scientific rigor have been recognized with appointments to World Health Organization, the National Institutes of Health, the Food and Drug Administration and the Wellcome Trust scientific advisory panels and boards.

As the leader of Baylor’s Vaccine and Treatment Evaluation Unit, El Sahly played a critical role in the response to the SARS CoV-2 pandemic, serving as the co-principal investigator and co-first author of the study that established the clinical efficacy of the Moderna mRNA vaccine in preventing COVID-19. El Sahly was selected as one of three national co-principal investigators of the phase 2 study of the Moderna vaccine and, in this role, made significant contributions to the study design and development of standardized outcomes. In addition, she and colleagues at Baylor initiated the Adaptive COVID-19 Treatment Trial, which proved the clinical efficacy of remdesivir in treating SARS CoV-2. Remdesivir remains the only antiviral medication approved for treating SARS CoV-2. El Sahly and colleagues also found that the use of remdesivir plus baricitinib, a targeted anti-inflammatory, improved outcomes in COVID-19 patients, especially those requiring oxygen.

In addition to her work during the pandemic, El Sahly has led clinical trials on influenza pandemic preparedness, the universal influenza vaccine, Zika virus infection, chikungunya and schistosomiasis.

Professor of Medicine; Chief, Section of Gastroenterology and Hepatology

The next DeBakey Research Award recipient is Dr. Fasiha Kanwal, professor of medicine and section chief of gastroenterology and hepatology and member of IQUEST and the Dan L Duncan Comprehensive Cancer Center.

Dr. Kanwal’s research focuses on clinical management and outcomes of patients with liver diseases, including hepatitis, nonalcoholic fatty liver disease and hepatocellular carcinoma. Her work has provided critical insight into the magnitude of quality problems in liver disease healthcare delivery.

For example, her clinical studies led to changes in the Centers for Medicare and Medicaid pay for performance programs and set the stage for the first large-scale quality improvement collaborative in cirrhosis.

Her work also examines the risk of hepatocellular cancer in patients with liver disease, and the American Gastroenterological Association  has incorporated her findings into clinical practice guidelines for screening and surveillance for hepatocellular carcinoma. Her studies support the development of risk-prediction models that combine clinical, electronic medical record and survey data to improve clinical risk stratification of patients with liver disease, including risk of progression to liver cancer.

Assistant Professor, Neuroscience

Dr. Nuo Li’s research aim is in understanding fundamental principles of how brain-wide circuits encode and maintain information, and how interactions across multiple brain regions allow the brain to prepare and initiate voluntary movements.

To probe the brain regions involved in behavior more effectively, Li has developed a novel high-throughput approach to studying and manipulating brain function during behaviors. This approach allows mice to engage in voluntary decision-making tasks in their home cages for months at a time without human intervention, allowing dozens of mice to be studied and tested at a single time.

This high-throughput approach is opening the ability to connect specific behaviors to the molecular properties and activities of identified neurons and neural circuits.

In addition to studying how a set of neural circuits interact to give rise to normal motor behavior, Nuo is also expanding his studies to examine the principles by which these same neural circuits also help process information to support cognitive functions.

Associate Professor, Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Department of Molecular and Cellular Biology

Dr. Sun’s research focuses on epigenomic regulatory mechanisms in the context of diabetes, autism and Alzheimer's disease. He studies how energy metabolism and neurocognition are regulated by diet, exercise, hormones and the circadian clock.

He has made seminal discoveries on how the central circadian clock regulates glucose metabolism. His team found a connection between the central clock dysfunction and the early-morning high blood sugar in type 2 diabetes patients, a prevalent condition known as the dawn phenomenon.

In addition, he and his team identified genetic variants in pediatric patients with autism, offering novel insight into how endocrine factors and metabolism regulate neurocognition through epigenomic mechanisms. This research has implications in understanding the pathogenesis of autism and neurodegenerative diseases associated with metabolic disorders.

Area: Neuroscience

Dr. Jeannie Chin is associate professor of neuroscience at Baylor. Her research uses a multidisciplinary approach to better understand cellular and network mechanisms underlying Alzheimer’s disease and seizures, as well as to identify potential therapeutic strategies for the treatment of these devastating diseases.

Memory deficits accompany many neurological disorders that present with seizures, such as Alzheimer’s disease. Dr. Chin’s lab recently published a series of papers that identify two major cellular and network mechanisms by which even infrequent seizures drive long-lasting changes in the brain. The first paper, published in Cell Reports in 2017, shows that seizures increase expression of the transcription factor deltaFosB, which epigenetically regulates expression of genes necessary for synaptic plasticity and memory formation, particularly c-fos and calbindin.

The second paper, published in Nature Medicine also in 2017, identified a molecular connection between memory and seizures in a mouse model of Alzheimer’s disease. She found that seizures can increase the levels of deltaFosB in the hippocampus, which results in a decrease in the levels of calbindin, a regulator of memory processes. Either preventing deltaFosB activity or experimentally increasing calbindin expression in the mice, improved the animals’memory. Dr. Chinfound the same changes in deltaFosB and calbindin levels in the hippocampus of Alzheimer’s disease patients and in the temporal lobe of epilepsy patients and proposed that these markers could potentially help assess clinical therapies for Alzheimer’s and other diseases with seizures.

Dr. Chin’s publication in Cell Reports in 2019 reveals a novel network mechanism by which recurrent seizures affect cognitive function in Alzheimer’s disease. Her lab compared the process of neurogenesis in normal mice with that in their mouse model of Alzheimer’s disease. They found that the processes are similar but, when seizures occur in mice with the disease, neurogenesis is acutely stimulated. The findings suggest that the seizures are deeply connected to the alterations in neurogenesis and cognitive functions both in Alzheimer’s disease and epilepsy.

View Dr. Chin's presentation

Area: Molecular and Human Genetics

Dr. Christine M. Eng is professor of molecular and human genetics and chief quality officer, vice president and chief medical officer of Baylor Genetics. Her main research interests are the development and application of molecular genetics to the diagnosis and treatment of genetic diseases.

For the past six years, Dr. Eng has served as principal investigator of the Undiagnosed Disease Network (UDN) sequencing core which is at Baylor College of Medicine and Baylor Genetics and provides exome and genome sequencing and RNASeq to the network. In 2018, the New England Journal of Medicine published the accomplishments of the first two years of the UDN. The analysis of the data showed the clinical utility of the diagnoses. For instance,58 percent of the individuals receiving a diagnosis had a change in medical care. Diagnoses were the result ofgenomic sequencing and clinical interpretation conducted by Dr. Eng’s team.

Dr. Eng’s group also has pioneered the development and clinical implementation of whole exome and whole genome sequencing in clinical medicine. In 2019, the New England Journal of Medicine published a letter showing that re-analysis of existing exome data over time significantly increased the molecular diagnostic rate, in some cases from 25 percent to 47 percent. Seventy-five percent of the new diagnoses derived from newly discovered gene-disease associations.This is an example of how her work has rapidly translated into benefits for patients and introduced positive changes into the practice of medicine.

Dr. Eng’s work has contributed to the development and clinical implementation of several innovative genetic diagnostic tests that are now considered part of routine clinical care,such as prenatal chromosome microarray analysis and whole exome sequencing. A paper published in Nature Medicine in 2019 described the development, validation and clinical implementation of a novel non-invasive prenatal assay that can detect new variants in 30 severe autosomal dominant disorders. To date, this is the only such clinical test available in the United States.and the research described by this paper represents a landmark in genomic medicine.

View Dr. Eng's presentation

Area: Molecular and Human Genetics

Dr. Greg Ira is professor of molecular and human genetics and a member of the Dan L Duncan Comprehensive Cancer Center at Baylor. He has earned recognition in the fields of DNA repair and recombination for his novel insights into basic molecular mechanisms linked to development and homeostasis and their implications for cancer and its treatment.

In the field of cancer biology, Dr. Ira’s work published in Oncogenesis (2017) suggests novel strategies to optimize cancer therapy. His lab conducted a screen to identify inhibitors of a DNA nuclease that is highly overexpressed in most cancers and has high potential as therapeutic target in this disease. The specific nuclease inhibitor Dr.Ira’s lab identified is successfully being used by many other laboratories and offers promising applications for cancer therapy.

In his 2018 paper published in Nature, Dr. Ira revealed a novel mechanism that increases our understanding of basic DNA biology. He showed that pieces of DNA from one chromosome,when not properly degraded,often end up being inserted into another chromosome. He reported the first mutant,yeast lacking the DNA-degrading enzyme called Dna2, in which any piece of one chromosome can jump to another chromosome. Similar DNA insertions are common in cancer genomes,in processes essential to generate diverse antibodies and likely contribute to the evolution of genes and chromosomes.

In the field of DNA recombination, Dr. Ira discovered a new function for the protein called Rad52. He showed that Rad52 binds to DNA and that this limits the unwinding of doble-stranded DNA and degradation of 5’strands during initial steps of homologous recombination,an important process in cell division. His finding also reveals how cells regulate the degradation of 5’DNA strands to maintain genome stability. This work was published in Molecular Cell in 2019.

View Dr. Ira's presentation

Area: Endocrinology, Diabetes and Metabolism

Dr. Dennis Villareal is professor of medicine in endocrinology, diabetes and metabolism. His research work represents major contributions to the fields of aging and obesity and has significantly influenced the care of older adults. Dr. Villareal’ s work highlights the value of weight loss and exercise to improve the medical complications of obesity in older adults, an increasing population that is particularly vulnerable to adverse outcomes because of frailty.

In his 2017 New England Journal of Medicine paper, Dr. Villareal showed that weight loss plus combined aerobic and resistance training is most effective in improving functional status of older adults with obesity. The lifestyle intervention protocols that he showed to be highly successful in older adults are accessible with the full text version of the article for dissemination to the public.

In addition, using a combination of molecular and cellular techniques, he recently published in the journal Cell Metabolism (2019) that in this older population, combined aerobic and resistance exercise is superior to either mode independently for improving muscle protein synthesis and myocellular quality, thereby maintaining muscle mass during weight-loss therapy.

To further comprehensively examine underlying mechanisms for the responses to specific exercise types during weight-loss therapy, he reported in the Journal of Bone and Mineral Research (2019) that,compared with aerobic exercise, resistance and combined aerobic and resistance exercise are associated with less bone loss. The results suggest that both resistance and combined aerobic and resistance exercise can be recommended to protect against bone loss during weight loss therapy of older adults with obesity.

Until recently, the appropriate management approach to obesity in older adults has been controversial. Dr Villareal’s work has shown that functional problems associated with obesity can be addressed safely through weight loss plus combined aerobic and resistance exercise, so that older individuals with obesity may be considered for such interventions.

View Dr. Villareal's presentation

Area: Pediatrics, Molecular and Human Genetics

Dr. Yong Xu is associate professor of pediatrics and of molecular and cellular biology. His lab investigates how neurons in the hypothalamus regulate appetite and satiety in mammals, issues associated with current important public health concerns, such as obesity, diabetes and eating disorders.

Dr. Xu’s work published in Nature Medicine in 2017 investigated a rare human disease, neonatal progeroid syndrome (NPS), which is characterized by loss of appetite and extreme leanness. NPS patients carry mutations that result in the loss of a blood circulating factor, a novel hunger hormone called asprosin. The researchers identified asprosin’s mechanism of action showing that it activates appetite-stimulating AgRP neurons and deactivates appetite-suppressing POMC neurons in the hypothalamus, which results in increased appetite.This work also provided a potential treatment strategy (asprosin supplement) and highlighted the possibility that asprosin-neutralizing approaches might help manage obesity.

Dr. Xu’s paper in Nature Communications (2018) revealed a completely new perspective on gender differences in body weight control. When male and female mice eat the same high-fat diet, the males gain significantly more weight than the females.Dr. Xu studied the POMC neurons in the hypothalamus, known to help maintain normal body weight. His lab compared the firing rate of electrical signals‒ a measure of how neurons communicate‒ between POMC neurons in males and females. They found that female POMC neurons normally fire faster than male neurons and this was associated with higher levels of expression of gene TAp63.

In 2019, Dr. Xu’s lab revealed in Nature Communications another piece of the complex puzzle of body weight control, this time showing a role for steroid receptor coactivator-1 (SRC-1)‒a protein a known to participate in the regulation of body weight, but whose precise role is not clear.They discovered that SRC-1 is highly expressed in POMC murine neurons in the hypothalamus and affects how these neurons regulate appetite. In collaboration with University of Cambridge’s Dr. I. Sadaf Farooqi, the team identified a group of severely obese children carrying rare genetic variants in the SRC-1 gene that produce dysfunctional proteins. Mice genetically engineered to express one of the human SRC-1 genetic variants found in obese children ate more and gained weight. This is the first report of SRC-1 playing a role in the hypothalamus in the context of body weight control.

View Dr. Xu's presentation

Area: Pediatrics – Hematology/Oncology

Associate Professor of Pediatrics, Division of Hematology/Oncology; Co-Director of TXCH Histiocytosis and Lymphoma Programs; Director of Research, Global HOPE; Member, Dan L Duncan Comprehensive Cancer Center

Dr. Allen’s work has focused on defining mechanisms of pathogenesis of Langerhans cell histiocytosis (LCH). LCH is characterized by granulomatous lesions with typical CD207+ dendritic cells that may arise as isolated lesions or disseminated life-threatening disease. Uncertain classification of LCH as a disorder of immune dysregulation versus neoplastic disease has blocked access to research support from National Cancer Institute-supported organizations, limiting opportunities to improve outcomes for patients through clinical trials. Dr. Allen’s research at Baylor College of Medicine has redefined LCH as a bona fide myeloid neoplastic disorder arising from hematopoietic precursors with activating MAPK pathway mutations. In a recent study published in Cancer, his team investigated the causes of LCH-associated neurodegeneration. They identified BRAF-V600E+ cells in peripheral blood and in brain biopsies of patients with LCH-ND, and patients treated with vemurafenib experienced dramatic clinical and radiologic improvement. This study determined that LCH-ND is a process caused by the same hematopoietic clones that drive systemic LCH lesion formation. While previous work used lineage tracing with MAPK pathway mutations to identify differentiation pathways of LCH, the functional consequences of MAPK activation in myeloid precursors were not known. In a study published in the Journal of Experimental Medicine, they determined that MAPK hyper-activation in myeloid dendritic cells abrogates CCR7 expression and up-regulates proteins that inhibit apoptosis, trapping activated pathologic DC resistant to cell death in lesions. The paradigm-changing work by Dr. Allen and colleagues has re-defined LCH as a myeloproliferative disorder. This work has not only uncovered novel therapeutic opportunities, but also it has contributed to the NCI including

Dr. Allen’s nomination was based on the following publications:

McClain KL, Picarsic J, Chakraborty R, Zinn D, Lin H, Abhyankar H, Scull B, Shih A, Lim KPH, Eckstein O, Lubega J, Peters TL, Olea W, Burke T, Ahmed N, Hicks MJ, Tran B, Jones J, Dauser R, Jeng M, Baiocchi R, Schiff D, Goldman S, Heym KM, Wilson H, Carcamo B, Kumar A, Rodriguez-Galindo C, Whipple NS, Campbell P, Murdoch G, Kofler J, Heales S, Malone M, Woltjer R, Quinn JF, Orchard P, Kruer MC, Jaffe R, Manz MG, Lira SA, Parsons DW, Merad M, Man TK, Allen CE. CNS Langerhans cell histiocytosis: Common hematopoietic origin for LCH-associated neurodegeneration and mass lesions. Cancer. 2018 Jun 15;124(12):2607-2620. doi: 10.1002/cncr.31348. Epub 2018 Apr 6. PubMed PMID: 29624648; PubMed Central PMCID: PMC6289302.

Hogstad B, Berres ML, Chakraborty R, Tang J, Bigenwald C, Serasinghe M, Lim KPH, Lin H, Man TK, Remark R, Baxter S, Kana V, Jordan S, Karoulia Z, Kwan WH, Leboeuf M, Brandt E, Salmon H, McClain K, Poulikakos P, Chipuk J, Mulder WJM, Allen CE, Merad M. RAF/MEK/extracellular signal-related kinase pathway suppresses dendritic cell migration and traps dendritic cells in Langerhans cell histiocytosis lesions. J Exp Med. 2018 Jan 2;215(1):319-336. doi: 10.1084/jem.20161881.

Allen C, Merad M, McClain K. Langerhans-Cell Histiocytosis. August 30, 2018. N Engl J Med 2018; 379:856-868. DOI: 10.1056/NEJMra1607548.

Area: Medicine

Vice Chair of Research, Department of Medicine; Chief, Section of Cardiology; Chief, Section of Cardiovascular Research; J.S. Abercrombie Chair; Professor of Medicine

Dr. Ballantyne is one of the foremost experts on lipids, atherosclerosis and heart disease prevention. He helped initiate “The Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial” (REDUCE- IT) and most recently, as lead investigator, found that patients with hypertriglyceridemia, despite statin therapy, had a lower risk of cardiovascular events when taking icosapent ethyl, a highly purified eicosapentaenoic acid (EPA) ethyl ester, compared to placebo. The findings were published in the New England Journal of Medicine. His latest research published in Circulation found that troponin I, a protein that is most commonly used to diagnose heart attack, can be detected with a new high-sensitivity assay in adults without prior cardiovascular disease or heart failure, and by adding this protein to the Pooled Cohort Equation, a commonly used risk prediction model, led to more accurate risk prediction for heart attack, stroke and heart failure hospitalization. In addition, his group is studying how genetic variation modifies the response to lipid therapy with the goal of developing personalized diet, lifestyle and pharmacotherapy based upon the genetic profile and clinical phenotype.

Dr. Ballantyne’s nomination was based on the following publications:

P Ridker, B Everett, T Thuren, J MacFadyen, W Chang, C Ballantyne, F Fonseca, J Nicolau, W Koenig, S Anker, J Kastelein, J Cornel, P Pais, D Pella, J Genest, R Cifkova, A Lorenzatti, T Forster, Z Kobalava, L Vida-Simiti, M Flather, H Shimokawa, H Ogawa, M Dellborg, P Rossi, R Troqua, P Libby, and R Glynn for the CANTOS Trial Group. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. September 21, 2017. N Engl J Med 2017; 377:1119-1131. DOI: 10.1056/NEJMoa1707914.

D Bhatt, P Steg, M Miller, E Brinton, T Jacobson, S Ketchum, R Doyle, R Juliano, L Jiao, C Granowitz, J Tardif, and C Ballantyne for the REDUCE-IT Investigator. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. January 3, 2019. N Engl J Med 2019; 380:11-22. DOI: 10.1056/NEJMoa1812792.

Saeed A, Nambi V, Sun W, Virani SS, Taffet GE, Deswal A, Selvin E, Matsushita K, Wagenknecht LE, Hoogeveen R, Coresh J, de Lemos JA, Ballantyne CM. Short-Term Global Cardiovascular Disease Risk Prediction in Older Adults. J Am Coll Cardiol. 2018 Jun 5;71(22):2527-2536. doi: 10.1016/j.jacc.2018.02.050. Epub 2018 Mar 10.

Area: Molecular Virology and Microbiology

Therapeutic Microbiology Laboratory; Professor of Molecular Virology and Microbiology; Alkek Center for Metagenomics and Microbiome Research; Dan L Duncan Comprehensive Cancer Center

Dr. Britton’s research and that of his lab is focused on the study of C. difficile, a bacterium that can cause serious infections in humans. The impact of C. diff, as it is commonly called, is staggering – about 14,000 deaths annually result from C. diff infection in the U.S. alone, and 200,000 worldwide. What’s particularly troubling is that antibiotics used to treat infections are actually a risk factor for C. diff infection by clearing away beneficial bacteria and allowing C. diff to gain a stronghold in the gastrointestinal tract. The Britton lab is interested in understanding the molecular pathogenesis of C. difficile, and recently their work has focused on how changes in food additives can drive the emergence of pandemic strains of pathogenic bacteria such as C. difficile in the human GI tract. Specifically, the work describes how the sugar trehalose and its incorporation into the Western diet has enabled the growth of two strains of the bacterium. This work, published in Nature with a follow-up review in the journal Gut Microbes, was widely reported throughout the world and is likely to inform FDA policy on the approval of such additives. To conduct the work of his lab, Dr. Britton has invented Mini-Bioreactor Arrays that enable the growth of intestinal communities, and this has greatly enhanced the ability to perform microbiome research at the College.

Dr. Britton’s nomination was based on the following publications:

Collins J, Robinson C, Danhof H, Knetsch CW, van Leeuwen HC, Lawley TD, Auchtung JM, Britton RA. Dietary trehalose enhances virulence of epidemic Clostridium difficile. Nature. 2018 Jan 18;553(7688):291-294. doi: 10.1038/nature25178. Epub 2018 Jan 3.

J Collins, H Danhof & R Britton (2019). The role of trehalose in the global spread of epidemic Clostridium difficile, Gut Microbes, 10:2, 204-209, DOI: 10.1080/19490976.2018.1491266.

H Velly, R Britton & G Preidis (2017). Mechanisms of cross-talk between the diet, the intestinal microbiome, and the undernourished host., Gut Microbes, 8:2, 98-112, DOI: 10.1080/19490976.2016.1267888.

Area: Molecular and Human Genetics

Professor of Molecular and Human Genetics; Director of Program in Quantitative and Computational Biosciences

Dr. Milosavljevic’s laboratory develops bioinformatics methods and advanced data platforms while contributing to the fields of genomics, clinical genomics, epigenomics and extracellular RNA communication. Using advanced web technologies, his lab provides data platforms and supports data coordination and analysis needs for NIH Common Fund projects and for the NIH-NHGRI Clinical Genome Resource (ClinGen). As part of the NIH Roadmap Epigenomics project, the lab established an ontogenetic tree of cellular differentiation, including global maps of cell-type specific regulatory elements and regulatory modules of coordinated activity and their likely activators and repressors. By analyzing allele-specific epigenome maps, the lab discovered nearly universal stochastic behavior of transcription factors, as evidenced by their methylation “footprints” at regulatory sites. The results provide a unifying model that links sequence-dependent allelic imbalances of the epigenome, stochastic switching at gene regulatory loci and disease-associated genetic variation. Dr. Milosavljevic’s lab leads the development of the FDA-recognized ClinGen database to inform clinical interpretation of genetic variation, and the lab currently serves as the Data Coordination Center for the NIH Extracellular RNA Communications project, which produced the ExRNA Atlas and developed the first comprehensive map of extracellular RNA in human biofluids. Developments in his work have been published in recently in Science, Genome Medicine and the American Journal of Human Genetics.

Dr. Milosavljevic’s nomination was based on the following publications:

Onuchic V, Lurie E, Carrero I, Pawliczek P, Patel RY, Rozowsky J, Galeev T, Huang Z, Altshuler RC, Zhang Z, Harris RA, Coarfa C, Ashmore L, Bertol JW, Fakhouri WD, Yu F, Kellis M, Gerstein M, Milosavljevic A. Allele-specific epigenome maps reveal sequence-dependent stochastic switching at regulatory loci. Science. 2018 Sep 28;361(6409):eaar3146. doi: 10.1126/science.aar3146. Epub 2018 Aug 23.

Patel RY, Shah N, Jackson AR, Ghosh R, Pawliczek P, Paithankar S, Baker A, Riehle K, Chen H, Milosavljevic S, Bizon C, Rynearson S, Nelson T, Jarvik GP, Rehm HL, Harrison SM, Azzariti D, Powell B, Babb L, Plon SE, Milosavljevic A; ClinGen Resource. ClinGen Pathogenicity Calculator: a configurable system for assessing pathogenicity of genetic variants. Genome Med. 2017 Jan 12;9(1):3. doi: 10.1186/s13073-016-0391-z.

Amendola LM, Jarvik GP, Leo MC, McLaughlin HM, Akkari Y, Amaral MD, Berg JS, Biswas S, Bowling KM, Conlin LK, Cooper GM, Dorschner MO, Dulik MC, Ghazani AA, Ghosh R, Green RC, Hart R, Horton C, Johnston JJ, Lebo MS, Milosavljevic A, Ou J, Pak CM, Patel RY, Punj S, Richards CS, Salama J, Strande NT, Yang Y, Plon SE, Biesecker LG, Rehm HL. Performance of ACMG-AMP Variant-Interpretation Guidelines among Nine Laboratories in the Clinical Sequencing Exploratory Research Consortium. Am J Hum Genet. 2016 Jun 2;98(6):1067-1076. doi: 10.1016/j.ajhg.2016.03.024. Epub 2016 May 12. Erratum in: Am J Hum Genet. 2016 Jul 7;99(1):247. PubMed PMID: 27181684; PubMed Central PMCID: PMC4908185.

Area: Molecular and Human Genetics

Assistant Professor of Molecular and Human Genetics

The Sardiello lab has quickly become a leader in the field of lysosome-autophagy biology that studies the waste disposal system of the cell and how its malfunction leads to the accumulation of cellular waste and lysosomal storage disorders, including Batten disease and other neurodegenerative conditions. He discovered that master transcription factor EB (TFEB) stimulates the cell to produce more lysosomes and degrade cellular waste more effectively and that TFEB activity is normally inhibited by Akt-mediated phosphorylation. These finding led to the discovery that small-drug inhibition of Akt promotes TFEB function. When tested in animal models of fatal lysosomal disorders, drug-induce inhibition of AKT ameliorated neuropathology and extended the life span of diseased animals. Published in Nature Communications in 2017, these findings are the foundation of a clinical trial for lysosomal storage diseases that is under development. In 2018, the Sardiello lab identified a novel and unexpected mechanism serving lysosomal biogenesis. CLN8, a protein mutated in Batten disease subtypes, is a cargo receptor that serves ER-to-Golgi trafficking of newly synthesized lysosomal enzymes. CLN8 deficiency results in impaired maturation of lysosomal enzymes, thereby causing lysosomal dysfunction. Published in Nature Cell Biology, this shows that the pathogenesis of Batten disease is rooted in impaired lysosome biogenesis, thus solving a long-lasting biomedical mystery and opening new therapeutic opportunities. In 2019, the Sardiello lab set the foundation for a better understanding and treatment of tuberous sclerosis, a disease characterized by the formation of tumors in multiple organs and glycogen accumulation. mTORC1, a protein complex that regulates cell metabolism, has long been considered the major driving force behind tuberous sclerosis. But in their report published in PNAS, Sardiello et al show that a second mechanism independent of mTORC1 also is involved. Defects in lysosome formation and in the digestion of cellular materials lead to glycogen accumulation. This could guide novel approaches to treat the disease in patients who partially respond to the treatments targeting mTORC1.

Dr. Sardiello’s nomination was based on the following publications:

Palmieri M, Pal R, Nelvagal HR, Lotfi P, Stinnett GR, Seymour ML, Chaudhury A, Bajaj L, Bondar VV, Bremner L, Saleem U, Tse DY, Sanagasetti D, Wu SM, Neilson JR, Pereira FA, Pautler RG, Rodney GG, Cooper JD, Sardiello M. mTORC1-independent TFEB activation via Akt inhibition promotes cellular clearance in neurodegenerative storage diseases. Nat Commun. 2017 Feb 6;8:14338. doi: 10.1038/ncomms14338. Erratum in: Nat Commun. 2017 Jun 13;8:15793. PubMed PMID: 28165011; PubMed Central PMCID: PMC5303831.

di Ronza A, Bajaj L, Sharma J, Sanagasetti D, Lotfi P, Adamski CJ, Collette J, Palmieri M, Amawi A, Popp L, Chang KT, Meschini MC, Leung HE, Segatori L, Simonati A, Sifers RN, Santorelli FM, Sardiello M. CLN8 is an endoplasmic reticulum cargo receptor that regulates lysosome biogenesis. Nat Cell Biol. 2018 Dec;20(12):1370-1377. doi: 10.1038/s41556-018-0228-7. Epub 2018 Nov 5. PubMed PMID: 30397314; PubMed Central PMCID: PMC6277210.

R Pal, Y Xiong, and M Sardiello. Abnormal glycogen storage in tuberous sclerosis complex caused by impairment of mTORC1-dependent and -independent signaling pathways. Proceedings of the National Academy of Sciences. Feb 2019, 116 (8) 2977-2986; DOI:10.1073/pnas.1812943116.

Area: Molecular and Cellular Biology

Associate Professor of Molecular and Cellular Biology and Member of the Center for Cell and Gene Therapy and the Stem Cells and Regenerative Medicine Center

Dr. Karl-Dimiter Bissig, associate professor of molecular and cellular biology, has focused his research on human liver disease and human disease modeling.

His three most recent works were published in Nature Communications. In his first paper, Bissig introduced the first xenograft model for metabolic liver disease. This mouse model more closely resembles human disease modeling, offering the ability to validate human experimental therapies. These new models are of particular relevance to macromolecular therapies, which are sequence or epitope specific, and cannot be validated in experimental animal models. This process supports the rapid translation of therapy from lab to clinical trials. His work was also featured in “research highlights” in Nature Reviews Endocrinology.

His follow-up study demonstrated for the first time human-specific drug metabolism in an animal model. He and his team were able to functionally inactivate murine cytochrome metabolism in humanized mice. His results will likely influence drug development and toxicity in a broad sense since most drugs are metabolized through the liver.

In his third paper, he and his colleagues developed metabolic pathway reprogramming uses CRISPR/Cas9 genome editing technology to inhibit an enzymatic pathway rather than to edit a disease-causing gene directly. This publication rescued a lethal phenotype using this technology, and in contrast to common small molecule drugs, required only a single intervention to rescue 100 percent of treated animals.

Dr. Bissig’s nomination was based on the following publications:

Bissig-Choisat B., Wang L, Legras X., Pradip K.S., Chen L., Bell P., Pankowicz F.P., Hill M.C., Barzi M., Kettlun Leyton C., Eastwood L.C., Kruse R.L., Himes R.W., Goss J.A., Wilson J.M., Chan L.L., Lagor W.R. and Bissig K.D. Development and Rescue of Human Familial Hypercholesterolemia in a Xenograft Mouse Model. Nature Communications 2015 Jun 17;6:7339. PMCID: PMC4557302.

Pankowicz FP, Barzi M, Legras X, Hubert L, Mi T, Tomolonis JA, Ravishankar M, Sun Q, Yang D, Borowiak M, Sumazin P, Elsea SH, Bissig-Choisat B, Bissig K.-D. Reprogramming metabolic pathways in vivo with CRISPR/Cas9 genome editing to treat hereditary tyrosinaemia. Nature Communications. 2016; 7:12642. PMCID: PMC5013601.

Barzi M, Pankowicz FP, Zorman B, Liu X, Legras X, Yang D, Borowiak M, Bissig-Choisat B, Sumazin P, Li F, and Bissig K.-D. A novel humanized mouse lacking murine P450 oxidoreductase for studying human drug metabolism. Nature Communications 2017 Jun 28;8(1):39 PMCID: PMC5489481.

Areas: Molecular and Human Genetics and Molecular and Cellular Biology

Assistant Professor in the Department of Molecular and Human Genetics and the Department of Molecular and Cellular Biology and is a Caroline Wiess Law Scholar at Baylor

Dr. Atul Chopra, assistant professor of molecular and human genetics and molecular and cellular biology, has concentrated his research on metabolism and energy homeostasis. He studies how energy enters the body and how it is used once it’s in the body, which usually involves an interplay between several organs and thus requires a whole-body experimental approach.

Chopra also works as a medical geneticist, focusing on patients with specific genetic problems related to consumption of energy, processing of energy and loss of energy. The problems usually manifest as a very high weight or very low weight. Since he was a medical resident at Baylor, he has been working to understand Neonatal Progeroid Syndrome, a condition characterized by energy balance problems resulting in extreme thinness and propensity for hypoglycemia.

His work led to the discovery of a new glucogenic and orexigenic hormone, asprosin. This hormone modulates hepatic glucose production and appetite stimulation using spatiotemporally distinct mechanisms when dietary fuel is unavailable. Chopra’s first paper on the glucogenic effect of asprosin in the liver was published in Cell and the second, which characterized the orexigenic effect of asprosin in the hypothalamus, was published in Nature Medicine.

This discovery of asprosin represents a new direction in the understanding of Marfan syndrome and the study of fibrillin. Asprosin has the potential for beneficial therapeutic impact of activity blockade via monoclonal antibody. In addition, antibodies targeting asprosin are showing considerable promise by acutely lowering blood glucose and appetite, leading to improvements in type II diabetes and obesity, respectively, over time.

Dr. Chopra’s nomination was based on the following publications:

Chase Romere, Clemens Duerrschmid, Juan Bournat, Petra Constable, Mahim Jain, Fan Xia, Pradip Saha, Romere C, Duerrschmid C, Bournat J, Constable P, Jain M, Xia F, Saha PK, Del Solar M, Zhu B, York B, Sarkar P, Rendon DA, Gaber MW, LeMaire SA, Coselli JS, Milewicz DM, Sutton VR, Butte NF, Moore DD, Chopra AR. Asprosin, a Fasting-Induced Glucogenic Protein Hormone, Cell 2016 Apr 21;165(3):566-579.

Duerrschmid C, He Y, Wang C, Li C, Bournat J, Romere C, Saha PK, Lee M, Phillips KJ, Jain M, Jia P, Zhao Z, Farias M, Wu Q, Milewicz DM, Sutton VR, Moore DD, Butte NF, Krashes MJ, Xu Y*, Chopra AR*. Asprosin is a Centrally-Acting Orexigenic Hormone. Nature Medicine. 2017 Dec;23(12):1444-1453 (* Equal Contribution).

Area: Molecular and Human Genetics

Assistant Professor of Molecular and Human Genetics and a McNair Scholar

Dr. Erez Lieberman Aiden, assistant professor of molecular and human genetics, is revolutionizing the study of how the human genome, at more than two meters long, folds up to fit inside the cell nucleus, and how this process governs gene regulation.

His recent work builds on the Hi-C method, which he invented in graduate school. By coupling DNA to DNA proximity ligation and high-throughput sequencing, Hi-C made it possible to solve the problem of how genomes fold. His lab has made a series of transformative discoveries: the compartmentalization of the human genome inside the nucleus; developing the first map of loops in the human genome and discovering how their positions are encoded; the demonstration that these loops form by extrusion, which has enormous consequences for the enzymology of DNA and which is now almost universally accepted; the ability to perform 3-D surgery on a genome by manipulating this code to control the extrusion process; and a method for assembling new, Human Genome Project-quality genomes for $1,000.

Dr. Aiden’s impact is easily quantified. His lab’s paper on mapping loops genome-wide for the first time has been cited more than 1,000 times, the most for any research article in Cell since 2014, and the 3-D genome browser it introduced has been used more than 100 million times. In the last year alone, the Aiden lab has published two papers in Cell, one of which was featured on the cover, and one in Science.

Dr. Lieberman’s nomination was based on the following publications:

Rao SS, Huntley MH, Durand NC, Stamenova EK, Bochkov ID, Robinson JT, Sanborn AL, Machol I, Omer AD, Lander ES, Erez Lieberman Aiden. A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell 2014.

Olga Dudchenko, Sanjit S. Batra*, Arina D. Omer*, Sarah K. Nyquist, Marie Hoeger, Neva C. Durand, Muhammad S. Shamim, Ido Machol, Eric S. Lander, Aviva Presser Aiden, Erez Lieberman Aiden. De novo assembly of the Aedes aegypti genome using Hi-C yields chromosome-length scaffolds. Science 2017.

Sanborn AL, Rao SS, Huang SC, Durand NC, Huntley MH, Jewett AI, Bochkov ID, Chinnappan D, Cutkosky A, Li J, Geeting KP, Gnirke A, Melnikov A, McKenna D, Stamenova EK, Lander ES, Erez Lieberman Aiden. Chromatin extrusion explains key features of loop and domain formation in wild-type and engineered genomes. PNAS 2015.

Area: Molecular and Human Genetics

Associate Professor of Molecular and Human Genetics and the Fyfe Endowed Chair in the Huffington Center on Aging

Dr. Meng Wang, associate professor of molecular and human genetics, has developed a successful innovative multidisciplinary research program that has produced original contributions to the fields of aging biology, lipid metabolism and reproductive biology.

Her laboratory uncovered the first lysosome-to-nucleus retrograde lipid messenger pathway, provided in-depth biochemical mechanisms for its action, and demonstrated its novel roles in regulating longevity, published in Science in 2015. Her work published in Nature Cell Biology and Cell also provided the first evidence for a novel communication mode between bacteria and their eukaryotic mitochondria, deciphered bacteria-derived metabolites mediating this ancient dialogue and their signaling mechanisms, and determined their vital effects on host’s lipid metabolism and longevity.

These studies have direct translational impact as they identify new nutrient-based approaches to increasing health span. In the area of reproductive fitness, she conducted the first genome-wide RNAi screen for gene inactivation that induces reproductive longevity, and identified a list of new genes associated with endocrine control of reproductive aging. Given the increasing trend of delayed childbearing in our current society, her discoveries are timely and lay critical foundations for improving reproductive health in humans.

Her groundbreaking contributions to technological innovation now allow for sensitive and specific trace of in vivo dynamics of small metabolites in living cells and organisms. These new technological advances have transformed how we investigate these bioactive small molecules and have revealed previously unknown physiological activities.

Dr. Wang’s nomination was based on the following publications:

Folick, A., Oakley, H.D., Yu, Y., Sanor, L., Kumari, M., Zechner, R., and Wang, M.C. (2015) Lysosomal signaling molecules regulate longevity in Caenorhabditis elegans. Science 347(6217): 83-86.

Bing, H., Sivaramakrishnan, P., Lin, C.J., Neve, I.A.A, Sowa, J.N., He, J., Tay, L.W.R., Sizovs, A., Du, G., Wang, J., Herman, C., Wang, M.C. (2017) Microbial genetic composition tunes host longevity. Cell 169(7): 1249-1262.

Yu, Y., Mutlu, A.S., Liu, H., Wang, M.C. (2017) High-throughput screens using photo-highlighting discover BMP signaling in mitochondrial lipid oxidation. Nat Commun 8: 865.

Area: Molecular and Cellular Biology

Associate Professor of Molecular and Cellular Biology

Dr. Xiang Zhang, associate professor of molecular and cellular biology, has focused the efforts of his lab in elucidating biological mechanisms and therapeutic strategies of metastasis, the major threat to the lives of solid cancer patients. These efforts resulted in the development of a set of unique techniques and models to study the interaction between microscopic metastases and various stromal components in different organs, particularly in the bone. These investigations have subsequently led to the discovery of osteogenic cells as the major microenvironmental components that promote early-stage of breast cancer-bone colonization, work that was published in Cancer Cell and selected as one of the journal’s eight best papers in 2015. Dr. Zhang is also studying the interactions between cancer cells and various immune cells and has published this work in Nature Cell Biology. Specifically, he has focused on the heterogeneity of the immune environment created by cancers with diverse genetic and epigenetic backgrounds and the establishment of a link between oncogenic mTOR signaling and accumulation of myeloid-derived suppressor cells. A breakthrough contribution to his field, which was published in a study in Nature, has been the discovery and characterization of a mutually regulatory loop between tumor vasculature and adaptive immunity. These findings profoundly enriched our understanding of tumor-microenvironment interaction and proposed compelling therapeutic strategies.

Dr. Wang’s nomination was based on the following publications:

Welte T, Kim IS, Tian L, Gao X, Wang H, Li J, Holdman XB, Herschkowitz JI, Pond A, Xia G, Kurley S, Nguyen T, Liao L, Dobrolecki LE, Pang L, Mo Q, Edwards DP, Huang S, Xin L, Xu J, Li Y, Lewis MT, Wang T, Westbrook TF, Rosen JM*, and Xiang H.-F. Zhang* (2016). Oncogenic mTOR signaling recruits myeloid-derived suppressor cells to promote tumor initiation. Nature Cell Biology 18(6):632-44. PMCID: PMC4884142.

Wang H., Yu C., Gao X., Welte T., Muscarella A.M., Zhao H., Zhao Z., Tao J., Lee B., Westbrook T.F., Wong S.T.C., Jin X., Rosen J.M., Osborne C.K., and Xiang H.-F. Zhang (2015). The Osteogenic Niche Promotes Early-Stage Bone Colonization of Disseminated Breast Cancer Cells. Cancer Cell. 27(2):193-210. PMCID: PMC4326554.

Tian L, Goldstein A, Wang H, Kim IS, Lo HS, Welte T, Sheng K, Dobrolecki LE, Zhang X, Putluri N, Phung T, Mani SA, Stossi F, Sreekumar A, Mancini MA, Zong C, Decker WK, Lewis MT, and Xiang H.-F. Zhang (2017). Mutual regulation of tumour vessel normalization and immunostimulatory reprogramming. Nature 544(7649):250-254.

Associate Professor and McNair Scholar Depts. of Molecular and Human Genetics, Neuroscience, and Program in Developmental Biology Baylor College of Medicine and Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital

Areas: Molecular and Human Genetics and Neuroscience

Dr. Benjamin Arenkiel, an associate professor of molecular and human genetics and neuroscience, has focused his research on improving our understanding of how the mammalian brain forms and maintains neural circuits. He recently described novel roles for neuropeptide signaling in synaptic remodeling within the adult mouse nervous system. In the area of circuit development, he discovered a new piece to the puzzle of how the brain organizes and processes information. The study, published in Nature Neuroscience, reports that although both depend on experience, excitatory and inhibitory neural maps mature in opposite ways. Excitatory neurons mature by sculpting and refining neural maps, while inhibitory neurons form maps that become broader with maturation. In addition, his contributions to the workings of the circuits of the mouse olfactory system have added to our understanding of how newly born neurons integrate into an existing network in the adult brain. His research, reported in Developmental Cell, shows that local corticotropin hormone signaling onto adult-born neurons promotes and/or stabilizes chemical synapses in the olfactory bulb, revealing a neuromodulatory mechanism for continued circuit plasticity, synapse formation, and integration of new neurons in the adult brain. Recently, a serendipitous finding triggered his interest in the neural mechanisms that govern feeding behavior. His lab discovered that cholinergic signaling in the basal forebrain exerts a strong influence on body weight control. Published in Nature, this is the first time that this neural circuit has been reported to influence feeding behavior, sensory processing, and stress, opening new research opportunities in these high-interest fields.

Dr. Arenkiel's nomination was based on the following publications:

Garcia I, Quast KB, Huang L, Herman AM, Selever J, Deussing JM, Justice NJ, Arenkiel BR. Local CRH signaling promotes synaptogenesis and circuit integration of adult-born neurons. Dev Cell. 2014 Sep 29;30(6):645-59. doi: 10.1016/j.devcel.2014.07.001. Epub 2014 Sep 4.

Herman AM, Ortiz-Guzman J, Kochukov M, Herman I, Quast KB, Patel JM, Tepe B, Carlson JC, Ung K, Selever J, Tong Q, Arenkiel BR. A cholinergic basal forebrain feeding circuit modulates appetite suppression. Nature. 2016 Oct 13;538(7624):253-256. doi: 10.1038/nature19789. Epub 2016 Oct 3.

Quast KB, Ung K, Froudarakis E, Huang L, Herman I, Addison AP, Ortiz-Guzman J, Cordiner K, Saggau P, Tolias AS, Arenkiel BR. Developmental broadening of inhibitory sensory maps. Nat Neurosci. 2017 Feb;20(2):189-199. doi: 10.1038/nn.4467. Epub 2016 Dec 26.

Professor and Cullen Foundation Endowed Chair | Chief, Division of Cardiothoracic Surgery and Vice-Chair of Surgery | Michael E. DeBakey Department of Surgery, Baylor College of Medicine

Chief, Adult Cardiac Surgery | Texas Heart Institute

Chief, Adult Cardiac Surgery Section | Associate Chief, Cardiovascular Service | Baylor St. Luke’s Medical Center

Dr. Joseph Coselli is professor of surgery and chief of cardiothoracic surgery. He has dedicated his career to optimizing the care of patients with aortic life-threatening thoracoabdominal aortic aneurisms, or TAAAs, focusing on reducing the risk of neurological and renal complications following TAAA repair. Through his study published in the Annals of Thoracic Surgery, he was able to demonstrate the value of using left heart bypass to reduce the problem of inadequate organ blood supply. In another study reported in the Journal of Vascular Surgery, he showed that cerebrospinal fluid drainage reduces the risk of spinal cord injury. In a report appearing in the Journal of Vascular Surgery, he addressed the problem of renal complications on a subsequent study demonstrating that providing cold crystalloid perfusion to the kidneys reduces the risk of renal problems. Dr. Coselli’s studies have made TAAA surgery safer. Patient outcomes have significantly improved and the practice of aortic surgery has changed. His multimodal approach to organ protection is now used in many major aortic centers around the world. In 2016, he published in the Journal of Thoracic and Cardiovascular Surgery the results of his 30 years of experience performing open TAAA repairs, presenting the largest series of patients treated for TAAAs ever reported.

Dr. Coselli’s nomination was based on the following publication(s):

Coselli JS, LeMaire SA, Preventza O, de la Cruz KI, Cooley DA, Price MD, Stolz AP, Green SY, Arredondo CN, Rosengart TK. Outcomes of 3309 thoracoabdominal aortic aneurysm repairs. J Thorac Cardiovasc Surg. 2016 May;151(5):1323-37. doi: 10.1016/j.jtcvs.2015.12.050. Epub 2016 Jan 14. PubMed PMID: 26898979.

2001 Recipient

Thoracoabdominal aortic aneurysm surgery: quest for organ protection and survival

Dr. Coselli received the award for his work in developing measures to reduce morbidity and mortality in thoracoabdominal aortic aneurysm. Dr. Coselli's research has focused upon the challenges encountered in the surgical treatment of patients suffering from aortic aneurysms, aortic dissection and Marfan syndrome. He has a particular interest in patients with extensive aneurysms involving both the chest and abdomen; i.e., thoracoabdominal aortic aneurysms. He has investigated the techniques to reduce the risks of surgical treatment of such aneurysms for both mortality and morbidity. The primary morbidities following such procedures include loss of function of the spinal cord and kidneys. In addition to curative operative intervention, organ protection and preservation are the focus of Dr. Coselli's research. To reduce spinal cord injury and its consequent development of paraplegia or paraparesis, perfusion beyond the location of repair using left heart bypass has been evaluated in a large series of patients. Cerebrospinal fluid drainage validated its favorable impact upon decreasing the incidence of paraplegia/paraparesis during a prospective randomized trial. Similarly, regarding preservation of kidney function, again using a prospective randomized evaluation, cold crystalloid perfusion reducing the kidney temperature was demonstrated to be superior to normothermic blood perfusion. Focusing upon mortality and major morbidity following thoracoabdominal aortic aneurysm repairs, Dr. Coselli has prospectively evaluated his large contemporary series to identify specific risk factors and develop predictive models for adverse outcomes. The latter serve as valuable tools for surgeons and patients deliberating operative intervention.

Dr. Coselli’s nomination was based on the following publications:

Coselli JS, LeMaire SA. Left heart bypass reduces paraplegia rates after thoracoabdominal aortic aneurysm repair. Ann Thorac Surg. 1999 Jun;67(6):1931-4; discussion 1953-8.

Coselli JS, LeMaire SA, Miller CC 3rd, Schmittling ZC, Koksoy C, Pagan J, Curling PE. Mortality and paraplegia after thoracoabdominal aortic aneurysm repair: a risk factor analysis. Ann Thorac Surg. 2000 Feb;69(2):409-14.

LeMaire SA, Miller CC 3rd, Conklin LD, Schmittling ZC, Koksoy C, Coselli JS. A new predictive model for adverse outcomes after elective thoracoabdominal aortic aneurysm repair. Ann Thorac Surg. 2001 Apr;71(4):1233-8.

Distinguished Service Professor and Cullen Endowed Chair of Human and Molecular Virology | Department of Molecular Virology and Microbiology | Department of Medicine – Gastroenterology and Hepatology

Dr. Mary Estes, a Distinguished Service professor of virology and microbiology, has concentrated her research on norovirus and rotavirus, the leading causes of food-borne gastroenteritis in children worldwide. In 2016, her paper in Science reported the development of the first replication system for noroviruses, solving a nearly 50 year old mystery and allowing researchers around the world to study the biology, pathogenesis and treatments against this major illness. The novel culture system consist of human intestinal epithelium preparations called enteroids or ‘mini-guts’ because under the microscope they look like a miniature intestine. In this system, researchers can now study human host-pathogen interactions, gaining insight into how noroviruses cause disease and answering questions such as why one strain of norovirus infects one person, but not another. On a previous work, she was the first to clone the norovirus genome and led the development of a new diagnostic test based on the viral proteins and genome. She also demonstrated that host susceptibility to norovirus infection depends on blood group antigens. Her lab also has developed virus-like particles, which are currently being tested as norovirus candidate vaccine in phase II clinical trials. In addition to the work with noroviruses, her lab has used the mini-guts to study rotavirus. In a 2017 publication in the Proceedings of the National Academy of Sciences, she revealed for the first time that rotavirus can fight back the immune response by antagonizing the interferon response at pre-and post-transcriptional levels. In 2016, a paper in the Journal of Virology was the first to establish a new model to study genetic susceptibility to rotavirus vaccines. Dr. Estes’ work with norovirus and rotavirus provides new opportunities for advancing basic and applied studies in viral gastrointestinal diseases.

Dr. Estes' nomination was based on the following publications:

Ettayebi K, Crawford SE, Murakami K, Broughman JR, Karandikar U, Tenge VR, Neill FH, Blutt SE, Zeng XL, Qu L, Kou B, Opekun AR, Burrin D, Graham DY, Ramani S, Atmar RL, Estes MK. Replication of human noroviruses in stem cell-derived human enteroids. J Science. 2016 Sep 23;353(6306):1387-1393. Epub 2016 Aug 25.

Saxena K, Simon LM, Zeng XL, Blutt SE, Crawford SE, Sastri NP, Karandikar UC, Ajami NJ, Zachos NC, Kovbasnjuk O, Donowitz M, Conner ME, Shaw CA, Estes MK. A paradox of transcriptional and functional innate interferon responses of human intestinal enteroids to enteric virus infection. Proc Natl Acad Sci U S A. 2017 Jan 24;114(4):E570-E579. doi: 10.1073/pnas.1615422114. Epub 2017 Jan 9.

Qu L, Murakami K, Broughman JR, Lay MK, Guix S, Tenge VR, Atmar RL, Estes MK. Replication of Human Norovirus RNA in Mammalian Cells Reveals Lack of Interferon Response. J Virol. 2016 Sep 12;90(19):8906-23. doi: 10.1128/JVI.01425-16. Print 2016 Oct 1.

1995 Recipient

Molecular dissection of gastroenteritis viruses and identification of a new mechanism of viral pathogenesis

Dr. Estes was honored for the molecular characterization of viruses responsible for gastroenteritis and identification of a viral enterotoxin responsible for the disease.

Dr. Estes’ nomination was based on the following publications:

Jiang X, Wang M, Wang K, Estes MK. Sequence and genomic organization of Norwalk virus. Virology. 1993 Jul;195(1):51-61.

Crawford SE, Labbe M, Cohen J, Burroughs MH, Zhou YJ, Estes MK. Characterization of virus-like particles produced by the expression of rotavirus capsid proteins in insect cells. J Virol. 1994 Sep;68(9):5945-52.

Tian P, Estes MK, Hu Y, Ball JM, Zeng CQ, Schilling WP. The rotavirus nonstructural glycoprotein NSP4 mobilizes Ca2+ from the endoplasmic reticulum. J Virol. 1995 Sep;69(9):5763-72.

Area: Molecular and Cell Biology

Tom Thompson Professor and Distinguished Leadership Professor and Distinguished Service Professor and Chair, Dept. Molecular and Cell Biology

Dr. Bert O’Malley, professor of molecular and cell biology, has focused his research on the molecular mechanisms that guide gene regulation in endocrinology and endocrine cancers. His work has improved our understanding of the molecular mechanisms by which hormones, receptors and coactivators contribute to the disease process. His pioneering work in this field has shown that intracellular hormones and cofactors act at the level of DNA to regulate the production of proteins and affect the function of the cell. Recent research reported in Molecular Cell was the first to solve the structure of a functional receptor-coactivator complex on DNA capable of regulating gene transcription in vitro. In addition, in a paper published in the Journal of Clinical Investigation, he showed that steroid receptor coactivator-2 (SRC-2), which is highly elevated in a variety of tumors, is likely implicated in metabolic coordination of cancer metastasis, opening the possibility of therapeutically targeting the SRC-2 pathway. His work with steroid receptor coactivator-3 (SRC-3), a prognostic marker for aggressive human breast cancer, showed that small-molecule inhibitors that directly bind SRC-3 cause selective degradation of the complex, hereby killing cancer cells with no observable toxicity. Small-molecule inhibitors represent a new type of oncologic drugs that target coactivators.

Dr. O'Malley's nomination was based on the following publications:

Yi P, Wang Z, Feng Q, Pintilie GD, Foulds CE, Lanz RB, Ludtke SJ, Schmid MF, Chiu W, O'Malley BW. Structure of a biologically active estrogen receptor-coactivator complex on DNA. Mol Cell. 2015 Mar 19;57(6):1047-58. doi: 10.1016/j.molcel.2015.01.025. Epub 2015 Feb 26.

Dasgupta S, Putluri N, Long W, Zhang B, Wang J, Kaushik AK, Arnold JM, Bhowmik SK, Stashi E, Brennan CA, Rajapakshe K, Coarfa C, Mitsiades N, Ittmann MM, Chinnaiyan AM, Sreekumar A, O'Malley BW. Coactivator SRC-2-dependent metabolic reprogramming mediates prostate cancer survival and metastasis. J Clin Invest. 2015 Mar 2;125(3):1174-88. doi: 10.1172/JCI76029. Epub 2015 Feb 9.

Wang L, Yu Y, Chow DC, Yan F, Hsu CC, Stossi F, Mancini MA, Palzkill T, Liao L, Zhou S, Xu J, Lonard DM, O'Malley BW. Characterization of a Steroid Receptor Coactivator Small Molecule Stimulator that Overstimulates Cancer Cells and Leads to Cell Stress and Death. Cancer Cell. 2015 Aug 10;28(2):240-52. doi: 10.1016/j.ccell.2015.07.005.

Area: Pediatrics and Rheumatology

Chief, Immunology, Allergy and Rheumatology | Director, Center for Human Immunobiology | Texas Children's Hospital
Professor of Pediatrics, Pathology and Immunology | Vice Chair for Research | Department of Pediatrics
Director, Pediatrician Scientist Training and Development Program | Baylor College of Medicine

Dr. Jordan Orange, professor of pediatrics and rheumatology, has concentrated his research on the study of primary immunodeficiency, and on the cell biology and deficiencies of natural killer (NK) cell defenses, a major player in the rejection of tumors and viral infections. His work has improved our understanding of the genetic bases and mechanisms of immunodeficiencies, underscoring the importance of NK cells defenses. Recent work, reported in Nature Genetics, applied cell biology, genomic and microscopy techniques, and revealed an unexpected molecular link between a vesicular transport protein and a hereditary autoimmune-mediated lung disease and arthritis. In 2016, a paper in the Journal of Clinical Investigation was the culmination of a 12 year study to determine the cause of an NK deficiency that makes patients susceptible to severe viral infections. Their investigation pinpointed two rare variants of the gene IRF8; one of them had not been reported before. The individuals carrying two defective IRF8 variants have fewer mature NK cells than those with the normal gene, and these fewer cells do not work properly. On another study, Dr. Orange has moved forward our understanding of how NK cells kill their targets. He had previously described that NK cells concentrate their lytic granules on the area of contact with the diseased cell, but why this concentration occurred was not clear. His paper published in the Journal of Cell Biology this year showed that by converging their lytic granules, NK cells improved the killing efficiency of their targets while preventing collateral damage to neighboring healthy cells.

Dr. Orange's nomination was based on the following publications:

Hsu HT, Mace EM, Carisey AF, Viswanath DI, Christakou AE, Wiklund M, Önfelt B, Orange JS. NK cells converge lytic granules to promote cytotoxicity and prevent bystander killing. J Cell Biol. 2016 Dec 19;215(6):875-889. Epub 2016 Nov 30.

Watkin LB, Jessen B, Wiszniewski W, Vece TJ, Jan M, Sha Y, Thamsen M, Santos-Cortez RL, Lee K, Gambin T, Forbes LR, Law CS, Stray-Pedersen A, Cheng MH, Mace EM, Anderson MS, Liu D, Tang LF, Nicholas SK, Nahmod K, Makedonas G, Canter DL, Kwok PY, Hicks J, Jones KD, Penney S, Jhangiani SN, Rosenblum MD, Dell SD, Waterfield MR, Papa FR, Muzny DM, Zaitlen N, Leal SM, Gonzaga-Jauregui C; Baylor-Hopkins Center for Mendelian Genomics., Boerwinkle E, Eissa NT, Gibbs RA, Lupski JR, Orange JS, Shum AK. COPA mutations impair ER-Golgi transport and cause hereditary autoimmune-mediated lung disease and arthritis. Nat Genet. 2015 Jun;47(6):654-60. doi: 10.1038/ng.3279. Epub 2015 Apr 20.

Mace EM, Bigley V, Gunesch JT, Chinn IK, Angelo LS, Care MA, Maisuria S, Keller MD, Togi S, Watkin LB, LaRosa DF, Jhangiani SN, Muzny DM, Stray-Pedersen A, Coban Akdemir Z, Smith JB, Hernández-Sanabria M, Le DT, Hogg GD, Cao TN, Freud AG, Szymanski EP, Savic S, Collin M, Cant AJ, Gibbs RA, Holland SM, Caligiuri MA, Ozato K, Paust S, Doody GM, Lupski JR, Orange JS. Biallelic mutations in IRF8 impair human NK cell maturation and function. J Clin Invest. 2017 Jan 3;127(1):306-320. doi: 10.1172/JCI86276. Epub 2016 Nov 28.

Professor, Department of Molecular and Human Genetics, and Department of Neuroscience | Director, Program in Developmental Biology

2016 Recipient

Area: Molecular & Human Genetics

Dr. Bellen received the award most recently due to his transformative observations linking metabolic alterations in mitochondrial function to a host of neurodegenerative diseases. He uses Drosophila as a model system to explore the functions of the nervous system. In so doing, he has developed state of the art technologies to empower the drosophila genetics community. At the same time, he has made seminal observations in neurodevelopment mechanisms including synaptic transmission and Notch signaling. Importantly, he has performed genetic screens in drosophila that have now empowered translational research in combination with human genetic gene discovery.

Dr. Bellen's nomination was based on the following publications:

Yamamoto S, Jaiswal M, Charng WL, Gambin T, Karaca E, Mirzaa G, Wiszniewski W, Sandoval H, Haelterman NA, Xiong B, Zhang K, Bayat V, David G, Li T, Chen K, Gala U, Harel T, Pehlivan D, Penney S, Vissers LE, de Ligt J, Jhangiani SN, Xie Y, Tsang SH, Parman Y, Sivaci M, Battaloglu E, Muzny D, Wan YW, Liu Z, Lin-Moore AT, Clark RD, Curry CJ, Link N, Schulze KL, Boerwinkle E, Dobyns WB, Allikmets R, Gibbs RA, Chen R, Lupski JR, Wangler MF, Bellen HJ. A drosophila genetic resource of mutants to study mechanisms underlying human genetic diseases. Cell. 2014 Sep 25;159(1):200-14. doi: 10.1016/j.cell.2014.09.002.

Nagarkar-Jaiswal S, Lee PT, Campbell ME, Chen K, Anguiano-Zarate S, Gutierrez MC, Busby T, Lin WW, He Y, Schulze KL, Booth BW, Evans-Holm M, Venken KJ, Levis RW, Spradling AC, Hoskins RA, Bellen HJ. A library of MiMICs allows tagging of genes and reversible, spatial and temporal knockdown of proteins in Drosophila. Elife. 2015 Mar 31;4. doi: 10.7554/eLife.05338.

Liu L, Zhang K, Sandoval H, Yamamoto S, Jaiswal M, Sanz E, Li Z, Hui J, Graham BH, Quintana A, Bellen HJ. Glial lipid droplets and ROS induced by mitochondrial defects promote neurodegeneration. Cell. 2015 Jan 15;160(1-2):177-90. doi: 10.1016/j.cell.2014.12.019. PubMed PMID: 25594180; PubMed Central PMCID: PMC4377295.

1995 Recipient

Dr. Hugo Bellen, professor of molecular and human genetics at Baylor College of Medicine and a Howard Hughes Medical Institute investigator.
Molecular mechanisms of neurotransmitter release: a genetic dissection

Dr. Bellen was recognized for the identification and genetic dissection of the molecular events responsible for the release of neurotransmitter from the nerve terminal and demonstration that synaptotagmin acts as a calcium detector in this process.

Dr. Bellen’s nomination was based on the following publications:

Littleton JT, Stern M, Schulze K, Perin M, Bellen HJ. Mutational analysis of Drosophila synaptotagmin demonstrates its essential role in Ca(2+)-activated neurotransmitter release. Cell. 1993 Sep 24;74(6):947-50.

Schulze KL, Littleton JT, Salzberg A, Halachmi N, Stern M, Lev Z, Bellen HJ. rop, a Drosophila homolog of yeast Sec1 and vertebrate n-Sec1/Munc-18 proteins, is a negative regulator of neurotransmitter release in vivo. Neuron. 1994 Nov;13(5):1099-108.

Littleton JT, Stern M, Perin M, Bellen HJ. Calcium dependence of neurotransmitter release and rate of spontaneous vesicle fusions are altered in Drosophila synaptotagmin mutants. Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):10888-92.

Schulze KL, Broadie K, Perin MS, Bellen HJ. Genetic and electrophysiological studies of Drosophila syntaxin-1A demonstrate its role in nonneuronal secretion and neurotransmission. Cell. 1995 Jan 27;80(2):311-20.

Area: Medicine - Gastroenterology

Professor | Chief, Gastroenterology and Hepatology

Dr. Hashem El-Serag received this award for his focus on the epidemiology and clinical outcomes of hepatocellular carcinoma (HCC) and esophageal adenocarcinoma. His research was the first report of the rising trends in HCC incidence and its mortality and later work was among the first to report the connection between hepatitis C and HCC. His work on esophageal adenocarcinoma and its precursor lesion, Barrett’s esophagus, was important for reporting on rising GERD rates and the link between obesity and EAC, as well as for uncovering the inverse association between H pylori infection and the risk of Barrett’s esophagus and esophageal adenocarcinoma.

Recent research, reported in Gastroenterology, makes innovative use of hundreds of thousands of lab tests available in the national Veterans Administration registries among patients with hepatitis C related cirrhosis (the most common and virulent risk factor for HCC), and identifies a robust but simple to apply algorithm that offers a much improved predictive value for the risk of HCC in the next 6 months. This algorithm if validated could have immediate clinical impact. Another recent paper featured the largest retrospective cohort study of patients with hepatitis C and was the first study to examine the effect of viral genotype on the risk of developing HCC, strongly linking genotype 3 to risk of HCC and making viral genotype 3 a treatment priority irrespective of severity of liver disease. Recent research on Barrett’s esophagus has examined several important risk factors for its presence and progression, moving beyond conventional measures of obesity (like BMI) and into potentially more pathogenically relevant indicators. This study found that the amount of visceral abdominal fat (rather than total or subcutaneous fat) is the strongest independent risk factor for Barrett’s esophagus, and used sophisticated measures developed by Dr. El-Serag and his research colleagues to uncover the mechanisms behind it, opening a new avenue for research into the pathogenesis and markers of Barrett’s esophagus related EAC.

Dr. El-Serag's nomination was based on the following publications:

Kanwal F, Kramer JR, Ilyas J, Duan Z, El-Serag HB. HCV genotype 3 is associated with an increased risk of cirrhosis and hepatocellular cancer in a national sample of U.S. Veterans with HCV. Hepatology. 2014 Jul;60(1):98-105. doi: 10.1002/hep.27095. Epub 2014 May 27.

El-Serag HB, Kanwal F, Davila JA, Kramer J, Richardson P. A new laboratory-based algorithm to predict development of hepatocellular carcinoma in patients with hepatitis C and cirrhosis. Gastroenterology. 2014 May;146(5):1249-55.e1. doi: 10.1053/j.gastro.2014.01.045. Epub 2014 Jan 23.

El-Serag HB, Hashmi A, Garcia J, Richardson P, Alsarraj A, Fitzgerald S, Vela M, Shaib Y, Abraham NS, Velez M, Cole R, Rodriguez MB, Anand B, Graham DY, Kramer JR. Visceral abdominal obesity measured by CT scan is associated with an increased risk of Barrett's oesophagus: a case-control study. Gut. 2014 Feb;63(2):220-9. doi: 10.1136/gutjnl-2012-304189. Epub 2013 Feb 13.

Associate Professor | Dan L Duncan Comprehensive Cancer Center and Department of Molecular and Cellular Biology Baylor College of Medicine

Area: Molecular and Cellular Biology

Dr. Li received the award for his concentrated his research on the design and application of bioinformatics algorithms to elucidate global epigenetic mechanisms in development and diseases such as cancer. Epigenetics is the study of modifications in gene activity that are not dependent on the underlying DNA sequence, including histone medications, alternative polyadenylation and DNA methylation. Dr. Li has developed a series of widely used bioinformatics algorithms for epigenetic sequencing data analysis. In close collaboration with experimental biologists, he has used big data bioinformatics analysis to gain novel biological insights in stem cells, aging and cancers.

In a Nature Genetics paper, Dr. Li discovered the first epigenetic signature for tumor suppressors in normal cells, through integrative analysis of more than 1,100 genome-wide epigenetic profiles, mutations from over 8,200 tumor-normal pairs and experimental data from clinical samples. A subsequent paper described the development of a novel bioinformatics solution called DaPars for Dynamic Analyses of Alternative Polyadenylation directly from RNA-Seq. In collaboration with the Wagner lab at University of Texas Health Science Center at Houston, Dr. Li used DaPars to identify CFIm25, a master APA regulator, as a glioblastoma tumor suppressor. In a third article, again in Nature Genetics, Dr. Li and the Goodell lab discovered extended regions of low methylation – DNA methylation canyons – that span conserved domains frequently containing transcription factors and are distinct from CpG islands and shores. Taken together, these findings have underscored the power of Dr. Li’s computational epigenetic research that can derive novel biological insights from epigenetic sequencing data.

Dr. Li's nomination was based on the following publications:

Chen K, Chen Z, Wu D, Zhang L, Lin X, Su J, Rodriguez B, Xi Y, Xia Z, Chen X, Shi X, Wang Q, Li W. Broad H3K4me3 is associated with increased transcription elongation and enhancer activity at tumor-suppressor genes. Nat Genet. 2015 Oct;47(10):1149-57. doi: 10.1038/ng.3385. Epub 2015 Aug 24.

Xia Z, Donehower LA, Cooper TA, Neilson JR, Wheeler DA, Wagner EJ, Li W. Dynamic analyses of alternative polyadenylation from RNA-seq reveal a 3'-UTR landscape across seven tumour types. Nat Commun. 2014 Nov 20;5:5274. doi: 10.1038/ncomms6274.

Jeong M, Sun D, Luo M, Huang Y, Challen GA, Rodriguez B, Zhang X, Chavez L, Wang H, Hannah R, Kim SB, Yang L, Ko M, Chen R, Göttgens B, Lee JS, Gunaratne P, Godley LA, Darlington GJ, Rao A, Li W, Goodell MA. Large conserved domains of low DNA methylation maintained by Dnmt3a. Nat Genet. 2014 Jan;46(1):17-23. doi: 10.1038/ng.2836. Epub 2013 Nov 24.

Associate Professor | Dan L Duncan Comprehensive Cancer Center and Department of Molecular and Cellular Biology Baylor College of Medicine

Area: Molecular Physiology & Biophysics

Dr. Martin received the award for his research team focusing on a fundamental question: Why, unlike other muscle types, does the heart muscle fail to regenerate itself after it is damaged? In a series of recent papers, Dr. Martin and his team discovered that the Hippo signaling pathway is a critical inhibitor of heart regeneration.

An important 2013 Development paper revealed that by manipulating the Hippo pathway, the mammalian heart can be induced to repair itself after injury. A 2015 Science Signaling paper reported another important step in understanding cardiac regeneration. In this paper, Dr. Martin and his group uncovered the genes that are regulated by the Hippo pathway in the regenerating myocardium and provided important insights to direct future research efforts. A recent paper in Nature reported a novel genetic pathway that interacts with the Hippo pathway and is important for the cardiomyocyte response to oxidative stress, and it provided new insight for potential therapeutic targets to treat heart failure. This work has opened a new field of research that focuses on investigating the possibility that endogenous cardiomyocytes can be induced to repair the heart after injury.

Dr. Martin's nomination was based on the following publications:

Tao G, Kahr PC, Morikawa Y, Zhang M, Rahmani M, Heallen TR, Li L, Sun Z, Olson EN, Amendt BA, Martin JF. Pitx2 promotes heart repair by activating the antioxidant response after cardiac injury. Nature. 2016 May 25;534(7605):119-23. doi: 10.1038/nature17959.

Morikawa Y, Zhang M, Heallen T, Leach J, Tao G, Xiao Y, Bai Y, Li W, Willerson JT, Martin JF. Actin cytoskeletal remodeling with protrusion formation is essential for heart regeneration in Hippo-deficient mice. Sci Signal. 2015 May 5;8(375):ra41. doi: 10.1126/scisignal.2005781.

Heallen T, Morikawa Y, Leach J, Tao G, Willerson JT, Johnson RL, Martin JF. Hippo signaling impedes adult heart regeneration. Development. 2013 Dec;140(23):4683-90. doi: 10.1242/dev.102798.

Associate Professor, Neuroscience

Dr. Tolias received the award for his focused research efforts on the organization of neural network interactions in the visual system, and their functional consequences for perception. Using both macaque and mouse models, his lab employs visually guided behaviors with the goal of understanding the computations underlying perception at the level of the individual neuron. The ability to continuously record individual neurons in an awake, behaving animal is an important technology, and the implications of this area of study are significant for the field of neuroscience and for an array of human diseases, including autism and schizophrenia. His record of publications in high-impact journals includes a recent paper in Science that demonstrates how the basic wiring of the local circuitry of the neocortex can be captured using a few connectivity rules that are recycled across the neocortex. This connectivity map will serve as a powerful blueprint to pinpoint specific circuit problems in animal models of disease. Also, Dr. Tolias is now leading the ambitious multi-institution project Machine Intelligence from Cortical Networks (MICrONS) which aims to reveal the computational building blocks of our brain and use them to create smarter learning machines. It is part of the broader BRAIN Initiative, launched in 2013 by President Obama with the goal of understanding devastating brain diseases and developing new technology, treatments and cures.

Dr. Tolias' nomination was based on the following publications:

Cadwell CR, Palasantza A, Jiang X, Berens P, Deng Q, Yilmaz M, Reimer J, Shen S, Bethge M, Tolias KF, Sandberg R, Tolias AS. Electrophysiological, transcriptomic and morphologic profiling of single neurons using Patch-seq. Nat Biotechnol. 2016 Feb;34(2):199-203. doi: 10.1038/nbt.3445. Epub 2015 Dec 21.

Froudarakis E, Berens P, Ecker AS, Cotton RJ, Sinz FH, Yatsenko D, Saggau P, Bethge M, Tolias AS. Population code in mouse V1 facilitates readout of natural scenes through increased sparseness. Nat Neurosci. 2014 Jun;17(6):851-7. doi: 10.1038/nn.3707. Epub 2014 Apr 20. PubMed PMID: 24747577; PubMed Central PMCID: PMC4106281.

Jiang X, Shen S, Cadwell CR, Berens P, Sinz F, Ecker AS, Patel S, Tolias AS. Principles of connectivity among morphologically defined cell types in adult neocortex. Science. 2015 Nov 27;350(6264):aac9462. doi: 10.1126/science.aac9462.