Katrin Chua

Katrin Chua, MD, PhD, Professor, Department of Medicine, Division of Endocrinology, Gerontology, & Metabolism, Stanford University School of Medicine

Research Description: Dr. Chua’s research explores how molecular mechanisms of chromatin regulation impact on diverse nuclear and epigenetic programs and how these mechanisms are de-regulated in aging and disease. Her lab focuses on the mammalian SIRT6 and SIRT7 genes, members of the evolutionarily conserved “Sirtuin” gene family that have key roles in regulating aging, lifespan, metabolism, inflammation, and stress resistance in many organisms. Dr. Chua’s group pioneered biochemical and genomic approaches that established that SIRT6 and SIRT7 are highly selective histone deacetylase enzymes and identified their first known physiologic substrates. They have uncovered novel mechanisms of SIRT6 in regulating genomic instability, telomere dysfunction, epigenetic aging-associated and inflammatory programs, and cellular senescence, and they have elucidated the functions and mechanisms of SIRT7 in epigenetic oncogenic programs, tumor growth and metastasis, metabolic homeostasis, and non-alcoholic fatty liver disease, among others. Dr. Chua has also had a longstanding interest in understanding cellular senescence and its roles in aging and age-related disease pathologies, and her lab has provided many insights into novel triggers of cellular senescence and their regulation by SIRT6 and SIRT7.

The Chua lab is currently exploring how SIRT6 and SIRT7 regulate cellular processes that are closely associated with the development and progression of diabetes, including glucose metabolism, insulin signaling, and inflammation. They are characterizing new mouse models and novel molecular mechanisms of SIRT6 and SIRT7 activity that may confer resistance to aging-associated changes in diabetes and metabolic syndrome.

Selected relevant publications (Stanford DRC members are in BOLD)::

  1. Tasselli L, Zheng W, and Chua KF (2017). SIRT6: novel mechanisms and links to aging and disease. Trends in Endocrinology and Metabolism 28(3): 168-185.

  2. Paredes S, Angulo-Ibanez M, Tasselli L, Carlson SM, Zheng W, Li TM, and Chua KF (2018). The epigenetic regulator SIRT7 guards against mammalian cellular senescence induced by ribosomal DNA instability. J. Biol Chem 293(28):11242-50.

  3. Wang WW, Angulo-Ibanez M, Lyu J, Kurra Y, Tong Z, Wu B, Zhang L, Sharma V, Zhou J, Lin H, Gao YQ, Li W, Chua KF, and Liu WR (2019). A click chemistry approach reveals the chromatin-dependent histone H3K36 deacylase nature of SIRT7. J Am Chem Soc 141(6):2462-2473.

  4. Li TM, Coan JP, Krajewski K, Zhang L, Elias JE, Strahl BD, Gozani O, and Chua KF (2019). Binding to medium and long chain fatty acyls is a common property of HEAT and ARM repeat modules. Scientific Reports 9(1):14226. doi: 10.1038/s41598-019-50817-6.

  5. Yuan G, Flores NM, Hausmann S, Lofgren SM, Kharchenko V, Angulo-Ibanez M, Sengupta D, Lu X, Czaban I, Azhibek D, Vicent S, Fischle W, Jaremko M, Fang B, Wistuba II, Chua KF, Roth JA, Minna JD, Shao NY, Jaremko L, Mazur PK and Gozani O (2021). Elevated NSD3 Histone Methylation Activity Drives Squamous Cell Lung Cancer. Nature, 590, 504–508.

  6. Zheng W, Tasselli L, Li TM, and Chua KF (2021). Mammalian SIRT6 Represses Invasive Cancer Cell Phenotypes through ATP Citrate Lyase (ACLY)-Dependent Histone Acetylation. Genes 12, 1460. https://doi.org/10.3390/genes12091460.