Positions
- Associate Professor
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Huffington Center On Aging
Baylor College of Medicine
Houston, TX US
- Associate Professor
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Molecular and Human Genetics
Baylor College of Medicine
- Member
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Dan L Duncan Comprehensive Cancer Center
Baylor College of Medicine
Houston, Texas United States
- Basic Science Representative
-
Faculty Senate
Baylor College of Medicine
Addresses
- Office - Huffington Center on Aging (Office)
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1 Baylor Plaza
N803.05, MS BCM230
Houston, TX 77030
United States
Phone: (713) 798-1565
weiwei.dang@bcm.edu
https://www.bcm.edu/research/faculty-labs/weiwei-dang-lab
Education
- PhD from Southern Illinois University
- 01/2006 - Carbondale, Illinois United States
- Post-Doctoral Fellowship at University of Pennsylvania
- 01/2011 - Philadelphia, Pennsylvania United States
Professional Interests
- Our lab uses yeast replicative aging as a model, together with human primary cell lines and adult stem cells, to study evolutionarily conserved epigenetic mechanisms during aging and development of age-related cancers
Professional Statement
Our laboratory is studying epigenetic regulation for aging and oncogenesis. Aging is the single greatest risk factor for diseases that are principal causes of mortality, including cardiovascular diseases, diabetes, neurodegenerative diseases and infectious diseases. A breakthrough in aging research resulting in even a moderate retardation of aging and a delay in the onset of age-associated diseases, such as cancer, would have tremendous impact on the quality of life for the public. However, aging and how it contributes to the development of age-associated diseases remain poorly understood. Epigenetic changes, including histone modifications and proteome, are critical regulatory mechanisms, involved in all developmental processes including aging and age-associated diseases. The goal of our research is to discover novel chromatin and proteomics regulation pathways that modulate longevity and regulate the development of age-associated diseases, such as cancer. These mechanistic studies will form the basis in future development of therapeutic targets for treating age-associated diseases and improving human health span.Replicative aging of budding yeast has been a powerful system for aging studies, providing fundamental genetic and molecular insights into both cellular and organismal aging. Studies of chromatin biology have also immensely benefited from the yeast model since it provides a uniquely tractable system for such studies and because many molecular mechanisms of chromatin are highly conserved from yeast to complex eukaryotes. We use the budding yeast replicative aging as a model to study how epigenetic regulations can modulate longevity. Our earlier work was among the first to demonstrate that changes in epigenetic markings can causatively alter lifespan in the budding yeast. We later discovered age-associated cryptic transcription and showed that suppressing it through epigenetic mechanisms can promote yeast lifespan. We have now extended these findings in worms and mammalian stem cells. Better stress response has been associated longevity in many experimental models. In another study, we revealed that a highly conserved chromatin remodeling enzyme regulates aging through stress response pathways in yeast and that this mechanism is also likely conserved in other eukaryotes. More recently, our team discovered a novel form of stress response called Chromatin Architectural Defect (CAD) response that becomes activated when nucleosomes are lost from chromatin, a phenomenon found in aged cells and tissues. Strikingly, moderately activating CAD response promotes longevity in yeast and the nematode C. elegans. These studies not only discovered novel molecular mechanisms regulating the aging process, but also provide new possibilities for intervention through epigenetic pathways. Furthermore, through a series of unbiased lifespan screens and other high throughput systems biology approaches, we have identified more chromatin regulation pathways that seem to also alter lifespan. Such pathways include those involved in transcription regulation, DNA damage response, cellular stress response, chromatin compaction and heterochromatin formation, etc. Further studies are currently carried out in our lab to elucidate the molecular mechanisms and their causal relationship to aging.
Stem cell aging and cellular senescence are important processes that contribute to the aging pathology and development of cancer. As a complement to our yeast replicative aging model, we are using mammalian primary cell lines and adult stem cells to study whether and how chromatin and epigenetic regulation pathways identified in yeast are involved in stem cell aging and cellular senescence. Our recently published study demonstrates that age-associated cryptic transcription that we initially discovered in yeast is also a hallmark of aged mammalian stem cells, as well as a broad range of tissues, providing valuable insights into the aging processes in mammals.
Websites
Selected Publications
- McCauley BS*, Sun L*, Yu R, Lee M, Liu H, Leeman DS, Huang Y, Webb AE, Dang W "Altered chromatin states drive cryptic transcription in aging mammalian stem cells." Nature Aging. 2021;
- Sun Y*, Yu R*, Guo H-B, Qin H, Dang W "A Quantitative Yeast Aging Proteomics Analysis Reveals Novel Aging Regulators." GeroScience. 2021;
- Yu R*, Cao X*, Sun L, Zhu J, Wasko B, Liu W, Crutcher E, Liu H, Jo MC, Qin L, Kaeberlein M, Han Z, Dang W "Inactivating histone deacetylase HDA promotes longevity by mobilizing trehalose metabolism." Nat Commun.. 2021;12:1981.
- Liu L, Yan Z, Osia BA, Twarowski J, Sun L, Kramara J, Lee R, Kumar S, Dang W, Ira G, Malkova A "Tracking break-induced replication shows that it stalls at roadblocks.." Nature. 2021;590:655-659.
- Yu R, McCauley BS, Dang W "Loss of chromatin structural integrity is a source of stress during aging.." Hum Genet.. 2020;139:371.
- Yu R, Sun L, Sun Y, Han X, Qin L, Dang W "Cellular Response to Moderate Chromatin Architectural Defects Promotes Longevity.." Sci Adv. 2019;5:eaav1165.
- Qin J, Rajaratnam R, Feng L, Salami J, Barber-Rotenberg J, Domsic J, Reyes-Uribe P, Liu H, Dang W, Berger SL, Villanueva J, Meggers E, Marmorstein R "Development of Organometallic S6K1 Inhibitors." J Med Chem. 2015;58(1):305-14. Pubmed PMID: 25356520
- Jo MC, Liu W, Dang W, Qin L "High-throughput analysis of yeast replicative aging using a novel microfluidic system." Proc Natl Acad Sci U S A. 2015;112(30):9364-9. Pubmed PMID: 26170317
- Sen P, Dang W, Donahue G, Dai J, Dorsey J, Cao X, Liu W, Cao K, Perry R, Lee JY, Wagner J, Gregory BD, Kaeberlein M, Kennedy BK, Boeke J, and Berger SL "H3K36 methylation promotes longevity by enhancing transcription fidelity." Genes Dev. 2015;29(13):1362-76. Pubmed PMID: 26159996
- Dang W, Sutphin GL, Dorsey JA, Otte GL, Cao K, Perry RM, Wanat JJ, Saviolaki D, Murakami CJ, Tsuchiyama S, Robison B, Gregory BD, Vermeulen M, Shiekhattar R, Johnson FB, Kennedy BK, Kaeberlein M, Berger SL "Inactivation of Yeast Isw2 Chromatin Remodeling Enzyme Mimics Longevity Effect of Calorie Restriction via Induction of Genotoxic Stress Response." Cell Metab. 2014 May 7;6(19):952-66. Pubmed PMID: 24814484
- McCauley BS, Dang W "Histone methylation and aging: Lessons learned from model systems." Biochim Biophys Acta. 2014;1839(12):1454-62. Pubmed PMID: 24859460
- McCormick MA, Mason AG, Guyenet SJ, Dang W, Garza RM, Ting MK, Moller RM, Berger SL, Kaeberlein M, Pillus L, La Spada AR, Kennedy BK "The SAGA Histone Deubiquitinase Module Controls Yeast Replicative Lifespan via Sir2 Interaction." Cell Rep. 2014 Jul 17;2(8):477-86. Pubmed PMID: 25043177
- Dang W "The controversial world of sirtuins." Drug Discovery Today: Technologies. 2014;12:e9-12. Pubmed PMID: 25027380
- Tsuchiyama S, Kwan E, Dang W, Bedalov A, Kennedy BK "Sirtuins in yeast: phenotypes and tools." Methods Mol Biol. 2013;(1077):11-37. Pubmed PMID: 24014397
- Yuan H, Rossetto D, Mellert H, Dang W, Srinivasan M, Johnson J, Hodawadekar S, Ding EC, Speicher K, Abshiru N, Perry R, Wu J, Yang C, Zheng YG, Speicher DW, Thibault P, Verreault A, Johnson FB, Berger SL, Sternglanz R, McMahon SB, Côté J, Marmorstein R "MYST protein acetyltransferase activity requires active site lysine autoacetylation." EMBO J. 2012;31(1):58-70. Pubmed PMID: 22020126
- Edwards CR, Dang W, Berger SL "Histone H4 lysine 20 of Saccharomyces cerevisiae is monomethylated and functions in subtelomeric silencing." Biochemistry. 2011;50(48):10473-83.. Pubmed PMID: 21985125
- Kozak ML, Chavez A, Dang W, Berger SL, Ashok A, Guo X, Johnson FB "Inactivation of the Sas2 histone acetyltransferase delays senescence driven by telomere dysfunction." EMBO J. 2010;29(1):158-70. Pubmed PMID: 19875981
- Dang W, Steffen KK, Perry R, Dorsey JA, Johnson FB, Shilatifard A, Kaeberlein M, Kennedy BK, Berger SL "Histone H4 lysine 16 acetylation regulates cellular lifespan." Nature. 2009;459(7248):802-7. Pubmed PMID: 19516333
- Sanders BD, Jackson B, Brent M, Taylor AM, Dang W, Berger SL, Schreiber SL, Howitz K, Marmorstein R "Identification and characterization of novel sirtuin inhibitor scaffolds." Bioorg Med Chem. 2009;17(19):7031-41. Pubmed PMID: 19734050
- Lin YY, Lu JY, Zhang J, Walter W, Dang W, Wan J, Tao SC, Qian J, Zhao Y, Boeke JD, Berger SL, Zhu H "Protein acetylation microarray reveals that NuA4 controls key metabolic target regulating gluconeogenesis." Cell. 2009;136(6):1073-84. Pubmed PMID: 19303850
- Dang W, Bartholomew B "Domain architecture of the catalytic subunit in the ISW2-nucleosome complex." Mol Cell Biol. 2007;27(23):8306-17. Pubmed PMID: 17908792
- Dang W, Kagalwala MN, Bartholomew B "The Dpb4 subunit of ISW2 is anchored to extranucleosomal DNA." J Biol Chem. 2007;282(27):19418-25. Pubmed PMID: 17491017
- Dang W, Kagalwala MN, Bartholomew B "Regulation of ISW2 by concerted action of histone H4 tail and extranucleosomal DNA." Mol Cell Biol. 2006;26(20):7388-96. Pubmed PMID: 17015471
- Kagalwala MN, Glaus BJ, Dang W, Zofall M, and Bartholomew B "Topography of the ISW2-Nucleosome Complex: Insights into Nucleosome Spacing and Chromatin Remodeling." EMBO J. 2004;23:2092-104. Pubmed PMID: 15131696
- Liu Y, Zheng J, Dang W, Ren H, Yu M, and Ru B "The Study of Direct ELISA and Competitive ELISA for Rabbit Metallothionein: Correlation of Induction with Zinc." Analusis. 2000;28:361-6.
Funding
- Regulation of longevity through maintenance of transcription fidelity - #R01AG052507 Grant funding from National Institute on Aging (NIA)
- Molecular mechanisms of cellular response to age-associated chromatin changes - #R01AG081347 Grant funding from National Institute on Aging (NIA)
- Developing and Validating a Novel Tau Toxicity Model in the Budding Yeast - #R03AG080423 Grant funding from National Institute on Aging (NIA)
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