Katrin Chua

Honors and Awards

• Ellison Medical Foundation New Scholar in Aging, Ellison Medical Foundation/AFAR (2008-2012)
• Paul Beeson Scholar in Aging Research, National Institute on Aging/American Federation for Aging Research (2006-)
• Pfizer Postdoctoral Fellow in Rheumatology/Immunology, Pfizer (2002-2005)
• Fellow of the Jane Coffin Childs Memorial Fund For Medical Research, Jane Coffin Childs Memorial Fund For Medical Research (2001-2002)
• Sackler Scholar in Psychobiology, Harvard University (1995-1996)

Professional Education

• Ph.D., Harvard Medical School Neuroscience/Cell Biology (2001)
• M.D., Harvard Medical School Medicine (2001)
• B.A., Harvard University Biochemistry/Molecular Biology (1991)

Postdoctoral Advisees

• Tao Hong, Federica Simeoni, Michelle Turski

Graduate & Fellowship Program Affiliations

• Cancer Biology

Web Site Links

• Chua Lab Website

Research Interests

Our lab is interested in understanding molecular processes that underlie aging and age-associated pathologies in mammals. We focus on a family of genes, the SIRTs, which regulate stress resistance and lifespan in lower organisms such as yeast, worms, and flies. In mammals, we recently uncovered a number of ways in which SIRT factors may contribute to cellular and organismal aging by regulating resistance to various forms of stress. We have now begun to characterize the molecular mechanisms by which these SIRT factors function. In particular, we are interested in how SIRT factors regulate chromatin, the molecular structure in which the DNA of mammalian genomes is packaged, and how such functions may link genome maintenance to stress resistance and aging.

Publications

• SIRT6 links histone H3 lysine 9 deacetylation to NF-kappaB-dependent gene expression and organismal life span. Kawahara TL,  Michishita E, Adler AS, Damian M, Berber E, Lin M, McCord RA, Ongaigui KC, Boxer LD, Chang HY, Chua KF.  Cell.  2009; 136 (1): 62-74
• Cell cycle-dependent deacetylation of telomeric histone H3 lysine K56 by human SIRT6. Michishita E,  McCord RA, Boxer LD, Barber MF, Hong T, Gozani O, Chua KF.  Cell Cycle.  2009; 8 (16): 2664-6
• SIRT6 stabilizes DNA-dependent Protein Kinase at chromatin for DNA double-strand break repair McCord RA,  Michishita E, Hong T, Berber E, Boxer LD, Kusumoto R, Guan S, Shi X, , Gozani O, Burlingame AL, Bohr VA, Chua KF.  Aging.  2009; 1 109-121
• SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin. Michishita E,  McCord RA, Berber E, Kioi M, Padilla-Nash H, Damian M, Cheung P, Kusumoto R, Kawahara TL, Barrett JC, Chang HY, Bohr VA, Ried T, Gozani O, Chua KF.  Nature.  2008; 452 (7186): 492-6
• Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Mostoslavsky R,  Chua KF, Lombard DB, Pang WW, Fischer MR, Gellon L, Liu P, Mostoslavsky G, Franco S, Murphy MM, Mills KD, Patel P, Hsu JT, Hong AL, Ford E, Cheng HL, Kennedy C, Nunez N, Bronson R, Frendewey D, Auerbach W, Valenzuela D, Karow M, Hottiger MO, Hursting S, Barrett JC, Guarente L, Mulligan R, Demple B, Yancopoulos GD, Alt FW.  Cell.  2006; 124 (2): 315-29
• Mammalian SIRT1 limits replicative life span in response to chronic genotoxic stress. Chua KF,  Mostoslavsky R, Lombard DB, Pang WW, Saito S, Franco S, Kaushal D, Cheng HL, Fischer MR, Stokes N, Murphy MM, Appella E, Alt FW.  Cell Metab.  2005; 2 (1): 67-76
• Mice lacking histone deacetylase 6 have hyperacetylated tubulin but are viable and develop normally. Zhang Y,  Kwon S, Yamaguchi T, Cubizolles F, Rousseaux S, Kneissel M, Cao C, Li N, Cheng HL, Chua K, Lombard D, Mizeracki A, Matthias G, Alt FW, Khochbin S, Matthias P.  Mol Cell Biol.  2008; 28 (5): 1688-701
• ING2 PHD domain links histone H3 lysine 4 methylation to active gene repression. Shi X,  Hong T, Walter KL, Ewalt M, Michishita E, Hung T, Carney D, Peña P, Lan F, Kaadige MR, Lacoste N, Cayrou C, Davrazou F, Saha A, Cairns BR, Ayer DE, Kutateladze TG, Shi Y, Côté J, Chua KF, Gozani O.  Nature.  2006; 442 (7098): 96-9
• DNA repair, genome stability, and aging. Lombard DB,  Chua KF, Mostoslavsky R, Franco S, Gostissa M, Alt FW.  Cell.  2005; 120 (4): 497-512
• Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Brunet A,  Sweeney LB, Sturgill JF, Chua KF, Greer PL, Lin Y, Tran H, Ross SE, Mostoslavsky R, Cohen HY, Hu LS, Cheng HL, Jedrychowski MP, Gygi SP, Sinclair DA, Alt FW, Greenberg ME.  Science.  2004; 303 (5666): 2011-5
• Developmental defects and p53 hyperacetylation in Sir2 homolog (SIRT1)-deficient mice. Cheng HL,  Mostoslavsky R, Saito S, Manis JP, Gu Y, Patel P, Bronson R, Appella E, Alt FW, Chua KF.  Proc Natl Acad Sci U S A.  2003; 100 (19): 10794-9
• Histone H2AX: a dosage-dependent suppressor of oncogenic translocations and tumors. Bassing CH,  Suh H, Ferguson DO, Chua KF, Manis J, Eckersdorff M, Gleason M, Bronson R, Lee C, Alt FW.  Cell.  2003; 114 (3): 359-70
• Transcription-targeted DNA deamination by the AID antibody diversification enzyme. Chaudhuri J,  Tian M, Khuong C, Chua K, Pinaud E, Alt FW.  Nature.  2003; 422 (6933): 726-30
• The influence of transcriptional orientation on endogenous switch region function. Shinkura R,  Tian M, Smith M, Chua K, Fujiwara Y, Alt FW.  Nat Immunol.  2003; 4 (5): 435-41
• The function of AID in somatic mutation and class switch recombination: upstream or downstream of DNA breaks. Chua KF,  Alt FW, Manis JP.  J Exp Med.  2002; 195 (9): F37-41
• Increased ionizing radiation sensitivity and genomic instability in the absence of histone H2AX. Bassing CH,  Chua KF, Sekiguchi J, Suh H, Whitlow SR, Fleming JC, Monroe BC, Ciccone DN, Yan C, Vlasakova K, Livingston DM, Ferguson DO, Scully R, Alt FW.  Proc Natl Acad Sci U S A.  2002; 99 (12): 8173-8
• An upstream AG determines whether a downstream AG is selected during catalytic step II of splicing. Chua K,  Reed R.  Mol Cell Biol.  2001; 21 (5): 1509-14
• Human step II splicing factor hSlu7 functions in restructuring the spliceosome between the catalytic steps of splicing. Chua K,  Reed R.  Genes Dev.  1999; 13 (7): 841-50
• The RNA splicing factor hSlu7 is required for correct 3' splice-site choice. Chua K,  Reed R.  Nature.  1999; 402 (6758): 207-10
• Phosphorylation of spliceosomal protein SAP 155 coupled with splicing catalysis. Wang C,  Chua K, Seghezzi W, Lees E, Gozani O, Reed R.  Genes Dev.  1998; 12 (10): 1409-14
• Cyclin E associates with components of the pre-mRNA splicing machinery in mammalian cells. Seghezzi W,  Chua K, Shanahan F, Gozani O, Reed R, Lees E.  Mol Cell Biol.  1998; 18 (8): 4526-36
• The splicing factor BBP interacts specifically with the pre-mRNA branchpoint sequence UACUAAC. Berglund JA,  Chua K, Abovich N, Reed R, Rosbash M.  Cell.  1997; 89 (5): 781-7