Dan L Duncan Comprehensive Cancer Center Shared Resources
The Shared Resources of the Dan L Duncan Comprehensive Cancer Center provide technical support services essential for basic, translational and clinical research studies of Cancer Center members. The NCI-designated P30 Cancer Center Support Grant (CCSG) provides funding support for advanced technologies, high-end instrumentation, data analysis, biostatistics and informatics services that would be difficult and too expensive for individual investigators or programs to develop and maintain on their own. Below are short descriptions of the CCSG supported Shared Resources plus a new emerging Geospatial Analysis and Health Outcomes Shared Resource (GHSR).
Advanced Microscopy and Image Informatics Shared Resource
Leader: Michael Mancini, Ph.D.
Co-Leader: Steven Ludtke, Ph.D.
The Advanced Microscopy and Image Informatics (AMII) Shared Resource provides state-of-the-art instrumentation, expert consultation, training, software tools, and data analysis for imaging-based cancer research projects with instruments that span the range of advanced fluorescent microscopy to cryo-electron microscopy and cryo-electron tomography (CryoEM/ET). For fluorescence-based microscopy, the AMII SR offers deconvolution and confocal microscopy and assay development for high throughput/high content imaging-based phenotypic or mechanistic screenings, including a halotomography platform for phenotypic analysis of unlabeled living cells. Small molecule libraries to known cancer therapeutic targets are available for screening by high content and single cell-oriented Cell Painting-based imaging assays. Cryo-electron microscopy (CryoEM), and cryo-electron tomography (CryoET) with cryo-focused ion beam milling (CryoFIB) services are also available through the AMII SR. CryoFIB permits submicron milling of tissues and cellular specimens with subsequent 3-D imaging at 5 nm resolution. CryoEM permits single particle structural studies of purified molecules and macromolecular assemblies to near atomic resolution. AMII represents a merger of Institutional Advanced Technology Integrated Microscopy Core (IMC) and Cryo Electron Microscopy Core. For more information, visit websites for each core: Integrated Microscopy Core and CryoEM Core.
Cell Processing and Vector Production Shared Resource
Leader: Natalia Lapteva, Ph.D.
Co-Leader: Zhuyong, Mei, Ph.D.
The Cell Processing and Vector Production (CPVP) Shared Resource provides manufacturing of therapeutic grade cellular therapy products and viral vector for use in early phase clinical trials. Products are prepared according to current Good Manufacturing Practices as required by the Food and Drug Administration. The CPVP provides the infrastructure and environment to prepare, test, and release these products for clinical use. The SR consists of a state-of-the-art facility with 22 manufacturing clean rooms and support facilities and highly experienced manufacturing and quality control and assurance staff. This CPVP works with investigators to develop clinical scale manufacturing procedures, releases test specifications and provides testing procedures, quality assurance oversight, and regulatory assistance for IND submissions. The CPVP is currently supporting 35 clinical trials, of which 25 are investigator-initiated cell therapy studies conducted under IND led by DLDCCC investigators. The CPVP SR manufactures products at a much-reduced cost compared to commercial manufacturing and testing entities. Most recently CPVP has implemented plasmid manufacturing and lentiviral vector manufacturing to allow investigators to transfer larger genetic cargoes, reduce product manufacturing times and to extend GMP-compliant gene and base editing methods for targeted changes in specific genomic loci of gene modified cell therapy products. For more information, visit the Cell Processing and Vector Production Shared Resource website.
Genetic Engineering Shared Resource
Leader: Jason Heaney, Ph.D.
Co-Leaders: Jun Xu, Ph.D., Christopher Ward, Ph.D. and Aleksandar Bajic, Ph.D.
The Genetic Engineering Shared Resource (GESR) is organized to meet the needs of Cancer Center investigators requiring use of experimentally demanding, state-of-the-art cell and mouse cancer models that require specialized techniques and a high degree of experimental ingenuity. The primary focus of the GESR is to provide DLDCCC investigators with highly customizable CRISPR/Cas9-based gene editing services in cells of their choice, from primary cells and established cell lines to cancer patient-derived induced pluripotent stem cells (iPSC) and in the mouse germline. Our genome editing services are comprehensive, starting with up-front consultation and project design and ending with allele validation. Services for cell model construction include reprogramming of patient-derived cancer cells into iPSC, generation of shRNA/cDNA/gRNA expressing cancer cell lines, and distribution of shRNA/cDNA clones and a Lenti-CRISPR-sgRNA library for investigators to generate their own cell models. Services for mouse model production include traditional and bacterial artificial chromosome transgenics and mouse embryonic stem cell-based gene targeting and chimera production. Moreover, we offer the latest in available mouse imaging modalities, including PET/SPECT/CT, X-Ray, MRI, NMR, luminescence, fluorescence, and ultrasound, to facilitate studies involving genetically engineered mice. To facilitate maintenance of SR user cell and mouse models, the GESR also provides cryopreservation and cryostorage services. The GESR represents a merger of Institutional Advanced Technology Cores including the Genetically Engineered Rodent Models, Advanced Cell Engineering & 3D Models (ACE-3M), Human Stem Cell and Mouse Phenotyping Cores. By operating these resources in a single, cohesive Shared Resource, the GESR enables investigators to employ a myriad of genetic engineering platforms, both in vitro and in vivo, that are often cost- and labor-prohibitive or simply not feasible for individual laboratories. This synergistic combination of expertise and resources makes GESR an invaluable asset to the DLDCCC. For more information visit websites for each ATC core: Genetically Engineered Rodent Models Core, Advanced Cell Engineering and 3D Models Core, Human Stem Cell and Neuronal Differentiation Core and Mouse Metabolism and Phenotyping Core.
Genomic, Spatial Transcriptomic, Epigenomic and Single Cell Shared Resource
Leader: Daniel Kraushaar, Ph.D.
Co-Leader: Mira Jeong, Ph.D.
The Genomic, Spatial Transcriptomic, Epigenomic, and Single Cell (GSTESC) Shared Resource addresses the growing need of cancer researchers to access state-of-art single cell, spatial and bulk genomics technologies that are not typically available in individual laboratories. The GSTESC offers services that allow for interrogation of genomic variation by genome sequencing, transcriptome profiling by RNA-seq, spatial transcriptomics as well as epigenomic profiling platforms. Somatic cancer cell lines widely used as cancer models, are homogenous and therefore suitable for bulk genomic assays. Single cell assays and spatial transcriptomics are more suitable for profiling highly heterogenous tumor tissues. Cost-economical and highly accurate sequencing is provided with our cutting-edge short-read Illumina sequencers including a recently acquired NovaSeq X. Third generation sequencers (Oxford Nanopore Promethion 24) that generate long reads facilitate detection of structural variants (SVs), copy number variations (CNVs) and transcript isoforms. The overarching goal of the GSTESC is to provide molecular profiling in bulk, at the single cell level and in spatial context using the most advanced technologies. We combine cross-disciplinary expertise, foster collaboration and offer streamlined services by partnering with other shared resources including the IBSR for 10X Genomics Visium spatial transcriptomics. Integrated data processing and analysis support is provided in part by GSTESC staff as well as through partnership with a software company and the Quantitative Science Shared Resource (QSSR). Storage of NGS data is supported by the BCM Office of Information Technology. The GSTESC strives to support DLDCCC investigators with consultation, access to high-end instrumentation and technology expertise at low cost. The GSTESC represents a merger of Institutional the Advanced Technology Genomic and RNA Profiling Core and the Single Cell Genomics Core. For more information visit the website for each core: Genomic and RNA Profiling Core (GARP) and Single Cell Genomics Core.
High-Parameter Cytometry Shared Resource
Leader: Christine Beeton, Ph.D.
Co-Leader: Joel Sederstrom, M.S.
The High-Parameter Cytometry Shared Resource (HPCSR) provides state-of-the-art instrumentation, expertise, and training for a wide range of cell sorting and analysis needs in a cost-effective manner for members of the Dan L Duncan Comprehensive Cancer Center. With the advent of novel tools and reagents, increased computational capacity, and more efficient instrumentation, this increasingly complex technology continues to develop rapidly, To keep pace with changing technologies, increased utilization, and growth of users, the HPCSR has expanded its space with new lab renovations, substantially upgraded existing equipment, and acquired new major equipment utilizing mass, imaging, high-parameter, and large and small particle cytometry. Current major instrumentation includes two mass cytometer and imaging systems, two high-parameter fluorescent cytometers, an imaging cytometer, six flow analyzers, four fluorescence-activated cell sorters, a first of it’s kind spectral and imaging cell sorter, and magnetic and large particle cell sorters. The operation model of the HPCSR is centered around training Cancer Center members in experimental design, instrument operation and data analysis to maximize knowledge and use of the full extent of core technologies for their cancer research projects. Trained users have 24/7 unassisted access to instruments, while assistance is available to others from nine full-time staff members. This organization maximizes access to instrumentation and cost efficiency for the Shared Resource and its’ users. This is an established Shared Resource of the Cancer Center that also serves as an Institutional Advanced Technology Cytometry and Cell Sorting Core. The name change for the CCSG reflects new capabilities for mass and imaging cytometry and high-parameter flow cytometry. For more information, visit the Cytometry and Cell Sorting Core website.
Integrated Biobanking Shared Resource
Leader: Michael Ittmann, M.D., Ph.D.
Co-Leader: Michael Scheurer, Ph.D.
The Integrated Biobanking Shared Resource (IBSR) fulfills the academic needs of Cancer Center investigators by providing access to biospecimens through coordinated general and targeted biospecimen acquisition from DLDCCC-affiliated clinics and by providing relevant expertise and technical resources to enhance basic, translational and clinical cancer biospecimen-based research activities. The IBSR personnel have extensive experience in pathology, epidemiology, biospecimen acquisition and processing, biobank maintenance, and sample distribution. In addition, personnel are trained in the various technical services offered including peripheral blood mononuclear cell preparation, DNA extraction, routine histology services, frozen sections, tissue microarray construction, immunohistochemistry, tissue microarray scanning, multiplex image analysis, and spatial transcriptomics. We also provide pathology consultation by expert pathologists for both human tissue specimens and mouse models, as well as risk factor questionnaire development and collection. Access to these IBSR resources is critical for biospecimen-based cancer investigation. The IBSR continually evolves to bring new technology and services to meet the changing needs of Cancer Center. For example, the IBSR has expanded collaborations with other Shared Resources to streamline spatial and other multi-omics studies that require cancer biospecimens. We also collaborate extensively with the Quantitative Sciences Shared Resource (QSSR) to maintain and catalog our biospecimen inventory availability to interested researchers in the DLDCCC, and to support our clinical annotation and risk factor database. The IBSR represents a merger of Institutional Advanced Technology Cores including the Human Tissue Acquisition and Pathology Core and the Population Sciences Biorepository Core. For more information, visit the Human Tissue Acquisition and Pathology Core and Population Sciences Biorepository Core websites.
Metabolomics Shared Resource
Leader: Nagireddy Putluri, Ph.D.
Co-Leader: Pradip Saha, Ph.D.
The Metabolomics Shared Resource (MSR) provides advanced mass spectrometry approaches and technologies, scientific consultation, and expert data analytics to support high-quality cancer metabolomics research. The MSR specializes in discovery, identification, characterization, and quantification of biomolecules, as well as measurement of activities of metabolic pathways, from a variety of biological specimens including tissues, cell lines, and body fluids. Support services include steady-state targeted metabolomics using Single Reaction Monitoring (SRM) Mass Spectrometry and the Biocrates technology with a capacity for quantification of up to 800 known metabolites; unbiased profiling for up to 2,000 metabolites using MS/MS databases to evaluate a broad range of biomolecules on a newly launched Orbitrap IQX Tribid MS; untargeted and targeted lipidomics for up to 1,000 lipids associated with cellular metabolism and nutrition; and metabolic flux analysis through isotope labeling of cell lines in vitro or animal tumors in vivo to monitor the activity of specific metabolic pathways. The ultimate goal of MSR is analysis of human samples from clinical investigational studies to identify predictive and prognostic biomarkers of disease progression during treatment, and the identification of novel metabolic therapeutic targets. The MSR is also supported as an Institutional Advanced Technology Core. Visit the Metabolomics Core website for more information: Metabolomics Core.
Patient-Derived Xenograft Shared Resource
Leader: Michael Lewis, Ph.D.
Co-Leader: Hugo Villanueva, Ph.D.
The Patient-Derived Xenograft Shared Resource (PDXSR) meets the needs of DLDCCC investigators in the use of state-of-the-art pre-clinical cancer models that includes patient-derived tumor xenografts (PDX) grown in either immunocompromised mice or rats, patient-derived tumor organoids (PDO), patient-derived xenograft organoids (PDxO), and 3D tumor growth on the chicken egg chorioallantoic membrane (CAM). All models provide renewable resources annotated with clinical history and available multi-omics characterization data that are accessible/mineable to assist users with their experimental design. Both PDxO and CAM 3D models can be adapted for screening investigational therapeutic compounds rapidly and efficiently, and they can be genetically engineered to enhance their utility as experimental models. All models are rigorously validated to “credential” that they accurately reflect the biology of the disease and or process under study. The PDXSR provides computational infrastructure to abstract, store, organize, retrieve, and display information so investigators can rationally select which model(s) to use and interpret their own experimental results. PDX models established from patients with bladder, breast, gynecological, head and neck, lung, or pancreas cancer, as well as glioblastoma, leukemia, or sarcoma, have whole-exome sequencing WES, RNAseq, and baseline proteomic profiling data available. When possible, matching patient germline WES data are also obtained and made available. In collaboration with other omics Shared Resources (PSR, MSR, GSTESC SR), PDXSR participates in a workflow pipeline for multi-omics analysis of PDX frozen tumors and matching human biopsies when available. Once omics data are collected and processed, they are made available on our PDX Portal “Insights” web-based data display and analysis tool. This website portal integrates patient- and PDX-related data to enable selection of models by investigators for pre-clinical research. An additional support service is training SR users on animal handling, surgical procedures and use of imaging instrumentation required to establish and perform experiments with PDX models. The PDXSR is also supported as an Institutional Advanced Technology Core. Visit the Patient-Derived Xenograft Core website for more information: Patient-Derived Xenograft Core.
Proteomics Shared Resource
Leader: Anna Malovannaya, Ph.D.
Co-Leader: Shixia Huang, Ph.D.
The goal of the Proteomics Shared Resource (PSR) is to support the research efforts of investigators to define perturbations of complex and dynamic protein signaling networks that are associated with development and progression of cancer as information that can be used for identification of novel potential therapeutic targets and biomarkers of response or resistance to specific therapies. The PSR provides two major technology platforms as support services. One is an antibody-based Reverse Phase Protein Array (RPPA) platform that measures >300 proteins and phosphoproteins of major oncogenic signaling pathways as well as histone epigenomic marks and chromatin regulators. The other is a large suite of high-end mass spectrometry-based platforms for expression profiling, profiling of post-translational modifications, and identification of protein-protein and protein complex interactions. Recognizing the challenges of “big data,” we further strive for excellence in data analysis and communication with our users. As such, PSR provides beginning-to-end service support packages to assist investigators with up-front study design and feasibility assessment, execution of experimental analysis by various technology platforms, specialized analysis and interpretation of data, troubleshooting, and decision-making in follow-up studies. PSR also leads support of a service for multi-omic profiling of PDX pre-clinical models and human clinical samples by coordinating sample quality control, sample processing, splitting and distribution to omics Shared Resources (PSR, GSTESC, MSR) for analysis, and coordinating data transfer from each data omics set to Quantitative Sciences Shared Resource (QSSR) for analysis and integration. Informatics tools have been developed for interpretation of proteomics data from mixed homologous species samples from patient-derived xenografts tumor model systems. PSR represents a merger of Institutional Advanced Technology Cores, the Mass Spectrometry Proteomics Core and the Antibody-Based Proteomics Cores. For more information, visit the Mass Spectrometry Proteomics and Antibody-Based Proteomics core websites.
Quantitative Science Shared Resource
Leader: Susan Hilsenbeck, Ph.D.
Co-Leaders: Cristian Coarfa, Ph.D., Tao Wang, Ph.D. and Chad Creighton, Ph.D.
The Quantitative Science Shared Resource (QSSR) serves the mission of the Cancer Center through assistance with state-of-the-art design, conduct, analysis, and interpretation of clinical, translational, and basic science studies, through bioinformatics and multi-omics data analysis methods. QSSR maintains a high-performance compute (HPC) cluster for data management and support for clinical, translational and basic research. Education and training, scientific review, data monitoring, and strategic planning are also essential functions provided by QSSR. This Shared Resource has been restructured from the broader Biostatistics and Informatics Shared Resource to reflect the focus on the quantitative science of biostatistics and bioinformatics and the HPC infrastructure. For more information, visit the Biostatistics and Informatics Shared Resource website.
Geospatial Analysis and Health Outcomes Shared Resource
Leader: Abiodun Oluyomi, Ph.D.
The Geospatial Analysis and Health Outcomes Shared Resource (GHSR) is a developing SR that supports population science research at the Duncan Cancer Center and among other BCM community researchers. Primarily, the shared resource guides the incorporation of population-level data into cancer research projects among DLDCCC members. The GHSR provides consultation and technical services to cancer center members with a focus on helping to drive catchment-focused research. For more information, visit the Geospatial Analysis and Health Outcomes Shared Resource website.