Catherine T. Yan

Beth Israel Deaconess Medical Center

Beth Israel Deaconess Medical Center
Phone: (617) 735-2459
Fax: (617) 735-2480


cyan@bidmc.harvard.edu

Catherine T. Yan

Beth Israel Deaconess Medical Center

EDUCATIONAL TITLES

  • Assistant Professor, Pathology, Harvard Medical School
  • Assistant Professor, Pathology, Beth Israel Deaconess Medical Center

DF/HCC PROGRAM AFFILIATION

Research Abstract

DNA double stranded breaks (DSBs) are critical lesions that can cause significant alterations in genetic information required for cell survival and proliferation. Aberrant DSB repair can impact on various pathologies, including acceleration of aging and the development of cancer. The broad research focus of the Yan laboratory is to elucidate the fundamental mechanisms that maintain genomic stability in mammalian cells. Our lab uses a number of mouse strains that are prone to cancer because they are deficient or are engineered to conditionally inactivate or significantly impair genes that encode factors involved in DSB detection and repair. In particular, we are investigating the functions of the DSB repair pathway nonhomologous end joining (NHEJ), which repairs broken DNA ends irrespective of sequence homology. Our interests are to understand how defective NHEJ impacts on immunodeficiency and aging related pathologies, including immune system decline, stem cell dysfunction and cancer. We seek to clarify the genomic stability maintenance functions of NHEJ, by elucidating aberrant NHEJ outcomes. We seek to identify novel factors that promote aberrant end-joining and oncogenic translocations in the absence of NHEJ; also their impact on genomic alterations and mechanisms that lead to the malignant phenotype and relevance to human pathologies. In this context, we are developing novel cell based, molecular and biochemical experimental approaches to create a roadmap of genomic alterations that promote malignant transformation. We are also adapting these experimental approaches to investigate how accumulated decline in genome stability control impacts on cellular and organismal aging and age-related disease.

 

Publications

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  • Newton RH, Lu Y, Papa A, Whitcher GH, Kang YJ, Yan C, Pandolfi PP, Turka LA. Suppression of T-cell lymphomagenesis in mice requires PTEN phosphatase activity. Blood 2015; 125:852-5. PubMed
  • Chen Z, Yan CT, Dou Y, Viboolsittiseri SS, Wang JH. The role of a newly identified SET domain-containing protein, SETD3, inoncogenesis. Haematologica 2012. PubMed
  • Eccleston J, Yan C, Yuan K, Alt FW, Selsing E. Mismatch repair proteins MSH2, MLH1, and EXO1 are important for class-switch recombination events occurring in B cells that lack nonhomologous end joining. J Immunol 2011; 186:2336-43. PubMed
  • Boboila C, Jankovic M, Yan CT, Wang JH, Wesemann DR, Zhang T, Fazeli A, Feldman L, Nussenzweig A, Nussenzweig M, Alt FW. Alternative end-joining catalyzes robust IgH locus deletions and translocations in the combined absence of ligase 4 and Ku70. Proc Natl Acad Sci U S A 2010; 107:3034-9. PubMed
  • Rucci F, Notarangelo LD, Fazeli A, Patrizi L, Hickernell T, Paganini T, Coakley KM, Detre C, Keszei M, Walter JE, Feldman L, Cheng HL, Poliani PL, Wang JH, Balter BB, Recher M, Andersson EM, Zha S, Giliani S, Terhorst C, Alt FW, Yan CT. Homozygous DNA ligase IV R278H mutation in mice leads to leaky SCID and represents a model for human LIG4 syndrome. Proc Natl Acad Sci U S A 2010; 107:3024-9. PubMed
  • Gostissa M, Yan CT, Bianco JM, Cogné M, Pinaud E, Alt FW. Long-range oncogenic activation of Igh-c-myc translocations by the Igh 3' regulatory region. Nature 2009; 462:803-7. PubMed
  • Wang JH, Gostissa M, Yan CT, Goff P, Hickernell T, Hansen E, Difilippantonio S, Wesemann DR, Zarrin AA, Rajewsky K, Nussenzweig A, Alt FW. Mechanisms promoting translocations in editing and switching peripheral B cells. Nature 2009; 460:231-6. PubMed
  • Wang JH,Alt FW,Gostissa M,Datta A,Murphy M,Alimzhanov MB,Coakley KM,Rajewsky K,Manis JP,Yan CT. Oncogenic transformation in the absence of Xrcc4 targets peripheral B cells that have undergone editing and switching. J Exp Med 2008; 205:3079-90. PubMed
  • Xie A,Hartlerode A,Stucki M,Odate S,Puget N,Kwok A,Nagaraju G,Yan C,Alt FW,Chen J,Jackson SP,Scully R. Distinct roles of chromatin-associated proteins MDC1 and 53BP1 in mammalian double-strand break repair. Mol Cell 2007; 28:1045-57. PubMed
  • Yan CT, Boboila C, Souza EK, Franco S, Hickernell TR, Murphy M, Gumaste S, Geyer M, Zarrin AA, Manis JP, Rajewsky K, Alt FW. IgH class switching and translocations use a robust non-classical end-joining pathway. Nature 2007; 449:478-82. PubMed
  • Chaudhuri J, Basu U, Zarrin A, Yan C, Franco S, Perlot T, Vuong B, Wang J, Phan RT, Datta A, Manis J, Alt FW. Evolution of the immunoglobulin heavy chain class switch recombination mechanism. Adv Immunol 2007; 94:157-214. PubMed
  • Yan CT, Kaushal D, Murphy M, Zhang Y, Datta A, Chen C, Monroe B, Mostoslavsky G, Coakley K, Gao Y, Mills KD, Fazeli AP, Tepsuporn S, Hall G, Mulligan R, Fox E, Bronson R, De Girolami U, Lee C, Alt FW. XRCC4 suppresses medulloblastomas with recurrent translocations in p53-deficient mice. Proc Natl Acad Sci U S A 2006; 103:7378-83. PubMed
  • Franco S, Gostissa M, Zha S, Lombard DB, Murphy MM, Zarrin AA, Yan C, Tepsuporn S, Morales JC, Adams MM, Lou Z, Bassing CH, Manis JP, Chen J, Carpenter PB, Alt FW. H2AX prevents DNA breaks from progressing to chromosome breaks and translocations. Mol Cell 2006; 21:201-14. PubMed
  • Yan C, Martinez-Quiles N, Eden S, Shibata T, Takeshima F, Shinkura R, Fujiwara Y, Bronson R, Snapper SB, Kirschner MW, Geha R, Rosen FS, Alt FW. WAVE2 deficiency reveals distinct roles in embryogenesis and Rac-mediated actin-based motility. EMBO J 2003; 22:3602-12. PubMed
  • 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. Increased ionizing radiation sensitivity and genomic instability in the absence of histone H2AX. Proc Natl Acad Sci U S A 2002; 99:8173-8. PubMed
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