Damian Yap

Overview
Epigenetics is the study of inherited changes in phenotype or gene expression caused by mechanisms other than changes in the DNA sequence. This involves histone modifications. My research project focuses on histone modifiers such as MLL5 and EZH2 (of the PRC2 complex). In particular, our research has elucidated the mechanism by which particular tumour-derived point mutations of EZH2 (EZH2Y641) can affect steady state levels of histone H3 Lys-27 trimethylation (H3K27me3) and hence gene expression. This may give us a clue as to how to treat certain kinds of lymphoma.

Studying diseases can be a challenge, since human disease tissue may be scarce and hard to obtain, so scientists often use cell lines and/or animal models. Another line of research seeks to develop relevant disease models from adult disease tissues. As a start, we are looking to see if there are other more efficient ways that adult cells can be reprogrammed to induced pluripotent cells which can then be used a source of cells for development of therapeutics, to test treatments or characterize the disease.

Education/Experience

  • Research Associate, Dept Pathology and Laboratory Medicine, UBC (2006-present)
  • Research Associate, Dept Oncology, University of Cambridge, UK (2002-2005)
  • PhD, DIC, Imperial College, University of London, UK (2001)
  • Graduate Student, Ludwig Institute for Cancer Research, Imperial College School of Medicine, St Mary’s Hospital, London, UK (1997-2001)
  • MBiochem (1:1, BDH Book prize), University of Oxford, UK (1997)
  • Current Research Projects (2011)

  • Epigenetics in Cancer and Disease (EZH2) (in collaboration with Keith Humphries (TFL), Gregg Morin (GSC), and Emila Lim (Marra Lab, GSC).
  • Epigenetics and haematopoiesis (MLL5) (in collaboration with Courteney Lai & Keith Humphries, TFL)
  • Mechanism of iPS cell reprogramming (Stem Cell Network collaboration with Nagy Lab, Toronto) iPS Project team: Adrian Wan, Jazmine Edwards.
  • Selected Publications

  • Yap DB, Walker DC, Prentice LM, McKinney S, Turashvili G, Mooslehner-Allen K, de Algara TR, Fee J, de Tassigny X, Colledge WH, Aparicio S. Mll5 Is Required for Normal Spermatogenesis. PLoS One. 2011;6(11):e27127. Epub 2011 Nov 1.
  • O’Connor MD, Wederell E, Robertson G, Delaney A, Morozova O, Poon SS, Yap D, Fee J, Zhao Y, McDonald H, Zeng T, Hirst M, Marra MA, Aparicio SA, Eaves CJ. Retinoblastoma-binding proteins 4 and 9 are important for human pluripotent stem cell maintenance. Exp Hematol. 2011 Aug;39(8):866-879.e1. Epub 2011 May 27. PubMed PMID: 21689726.
  • Yap DB, Chu J, Berg T, Schapira M, Cheng SW, Moradian A, Morin RD, Mungall AJ, Meissner B, Boyle M, Marquez VE, Marra MA, Gascoyne RD, Humphries RK, Arrowsmith  CH, Morin GB, Aparicio SA. Somatic mutations at EZH2 Y641 act dominantly through  a mechanism of selectively altered PRC2 catalytic activity, to increase H3K27 trimethylation. Blood. 2010 Dec 29. [Epub ahead of print] PubMed PMID: 21190999.
  • Morin RD, Johnson NA, Severson TM, Mungall AJ, An J, Goya R, Paul JE, Boyle M, Woolcock BW, Kuchenbauer F, Yap D, Humphries RK, Griffith OL, Shah S, Zhu H, Kimbara M, Shashkin P, Charlot JF, Tcherpakov M, Corbett R, Tam A, Varhol R, Smailus D, Moksa M, Zhao Y, Delaney A, Qian H, Birol I, Schein J, Moore R, Holt R, Horsman DE, Connors JM, Jones S, Aparicio S, Hirst M, Gascoyne RD, Marra MA. Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin. Nat Genet. 2010 Feb;42(2):181-5. Epub 2010 Jan 17. PubMed PMID: 20081860; PubMed Central PMCID: PMC2850970.
  • Heuser M, Yap DB, Leung M, de Algara TR, Tafech A, McKinney S, Dixon J, Thresher R, Colledge B, Carlton M, Humphries RK, Aparicio SA. Loss of MLL5 results in pleiotropic hematopoietic defects, reduced neutrophil immune function, and extreme sensitivity to DNA demethylation. Blood. 2009 Feb 12;113(7):1432-43.  Epub 2008 Oct 14. PubMed PMID: 18854576.
  • Contact
    BC Cancer Research Centre
    675 West 10th Ave
    Vancouver BC, V5Z 1L3, Canada
    E: dyap [at] bccrc [dot] ca
    P: +1 604 675 8000 x 7558