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Email

Weiwei.Dang@bcm.edu

Positions

Associate Professor

Huffington Center On Aging
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Houston, TX US

Associate Professor

Molecular and Human Genetics
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Member

Dan L Duncan Comprehensive Cancer Center
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Houston, Texas United States

Basic Science Representative

Faculty Senate
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Addresses

Office - Huffington Center on Aging (Office)

1 Baylor Plaza
N803.05, MS BCM230
Houston, TX 77030
United States
Phone: (713) 798-1565
weiwei.dang@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.

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)