SPEAKERS
Ashok R. Venkitaraman
AFFILIATION:
The Cancer Science Institute of Singapore National University of Singapore School of Medicine
POSITION TITLE:
Director and Distinguished Professor
EDUCATION/TRAINING:
1984 – 1988 University College London & The Charing Cross Medical School London, UK
Lady Tata Trust Memorial Fellow PhD [Supervisor: Professor Sir Marc Feldmann]
1977– 1983 The Christian Medical College, Vellore Vellore, India, MB., BS
HONORS:
2001 Elected to the U.K. Academy of Medical Sciences (F.Med.Sci)
2004 Elected to the European Molecular Biology Organization (EMBO)
2018 The Basser Global Prize
2005 Myers Distinguished Lecturer, Sackler School of Medicine, Tel-Aviv University, Israel
2005 General Motors Cancer Research Fund Annual Meeting Lecturer, Washington DC
2008 ERBI Award for Innovation in Drug Discovery
2008 The Ranbaxy Award for Medical Research
2011 Cambridge-Hamied Visiting Lecturer
2012 John H. Blaffer Lecturer, MD Anderson Cancer Center, Houston, Texas
2012 Visiting Professor, National Centre for Biological Sciences & inStem, Bangalore
2014 Bhupat & Jyoti Mehta Foundation Visiting Professor, Indian Institute of Technology, Madras
2018 President’s Research Seminar Lecturer, Memorial Sloan-Kettering Cancer Center, NY, NY
2019 Distinguished Visiting Professor, The National University of Singapore
RESEARCH INTERESTS:
PUBLICATIONS:
TWENTY KEY PUBLICATIONS
Cancer susceptibility and the biological functions of BRCA2
1. Patel, K.J., Yu, V.P., Lee, H., Corcoran, A., Thistlethwaite, F.C., Evans, M.J., Colledge, W.H., Friedman, L.S.,Ponder, B.A. & Venkitaraman, A.R. Involvement of Brca2 in DNA repair. Mol Cell 1, 347-57 (1998).
2. Yu, V.P., Koehler, M., Steinlein, C., Schmid, M., Hanakahi, L.A., van Gool, A.J., West, S.C. &
Venkitaraman, A.R. Gross chromosomal rearrangements and genetic exchange between nonhomologous
chromosomes following BRCA2 inactivation. Genes Dev 14, 1400-6 (2000).
3. Lee, H., Trainer, A.H., Friedman, L.S., Thistlethwaite, F.C., Evans, M.J., Ponder, B.A. & Venkitaraman, A.R.Mitotic checkpoint inactivation fosters transformation in cells lacking the breast cancer susceptibility gene,Brca2. Mol Cell 4, 1-10 (1999).
4. Pellegrini, L., Yu, D.S., Lo, T., Anand, S., Lee, M., Blundell, T.L. & Venkitaraman, A.R. Insights into DNA
recombination from the structure of a RAD51-BRCA2 complex. Nature 420, 287-93 (2002).
5. Yu, D.S., E. Sonoda, S. Takeda, C.L. Huang, L. Pellegrini, T.L. Blundell, and A.R. Venkitaraman. Dynamiccontrol of Rad51 recombinase by self-association and interaction with BRCA2. Mol Cell. 12, 1029-41(2003).
6. Lomonosov, M., Anand, S., Sangrithi, M., Davies, R. & Venkitaraman, A.R. Stabilization of stalled DNA
replication forks by the BRCA2 breast cancer susceptibility protein. Genes Dev 17, 3017-22 (2003).
7. Shivji, M.K., Mukund, S.R., Rajendra, E., Chen, S., Short, J.M., Savill, J., Klenerman, D. & Venkitaraman,A.R. The BRC repeats of human BRCA2 differentially regulate RAD51 binding on single- versus double-stranded DNA to stimulate strand exchange. Proc Natl Acad Sci USA 106, 13254-9 (2009).
8. Jeyasekharan, A.D., Liu, Y., Hattori, H., Pisupati, V., Jonsdottir, A.B., Rajendra, E., Lee, M.,
Sundaramoorthy, E., Schlachter, S., Kaminski, C.F., Ofir-Rosenfeld, Y., Sato, K., Savill, J., Ayoub, N. &
Venkitaraman, A.R. A cancer-associated BRCA2 mutation reveals masked nuclear export signals controllinglocalization. Nature Struct Mol Biol 20, 1191-8 (2013).
9. Shivji, M.K., Renaudin, X., Williams, C., Venkitaraman, A.R. (2018) BRCA2 regulates transcription
elongation by RNA polymerase II to prevent R-loop accumulation. Cell Rep 22, 1031-39.
Metabolic bypass of Knudson’s two-hit paradigm for tumour suppression by BRCA2
10. Skoulidis, F., Cassidy, L.D., Pisupati, V., Jonasson, J.G., Bjarnason, H., Eyfjord, J.E., Karreth, F.A., Lim, M.,Barber, L.M., Clatworthy, S.A., Davies, S.E., Olive, K.P., Tuveson, D.A. & Venkitaraman, A.R. GermlineBrca2 heterozygosity promotes Kras(G12D) -driven carcinogenesis in a murine model of familial pancreaticcancer. Cancer Cell 18, 499-509 (2010).
11. Tan, S. L. W., Chadha, S., Liu, Y., Gabasova, E., Perera, D., Ahmed, K., Constantinou, S., Renaudin, X.,
Lee, M., Aebersold, R. & Venkitaraman, A. R. (2017) A Class of Environmental and Endogenous Toxins
Induces BRCA2 Haploinsufficiency and Genome Instability. Cell 169, 1105-1118.
12. Kong LR, Gupta K, Wu AJ, Perera D, Ivanyi-Nagy R, Moiz Ahmed SM, Tan TZ, Tan SLW, Fuddin A,
Sundaramoorthy E, Shiqing Goh GS, Wong RTX, Costa ASH, Oddy C, Wong H, Patro CP, Kho YS, Huang
XZ, Choo J, Shehata M, Lee SC, Goh BC, Frezza C, Pitt JJ, Venkitaraman AR. A glycolytic metabolite
bypasses ‘‘two-hit’’ tumor suppression by BRCA2. (2024) Cell 187, 2269–2287.
Tumour suppressive pathways maintaining chromosome integrity
13. Sangrithi, M.N., Bernal, J.A., Madine, M., Philpott, A., Lee, J., Dunphy, W.G. & Venkitaraman, A.R.
Initiation of DNA replication requires the RECQL4 protein mutated in Rothmund-Thomson syndrome. Cell121, 887-98 (2005).
14. Ayoub, N., Jeyasekharan, A.D., Bernal, J.A. & Venkitaraman, A.R. HP1-beta mobilization promotes
chromatin changes that initiate the DNA damage response. Nature 453, 682-6 (2008).
15. Garnett, M.J., Mansfeld, J., Godwin, C., Matsusaka, T., Wu, J., Russell, P., Pines, J. & Venkitaraman, A.R.UBE2S elongates ubiquitin chains on APC/C substrates to promote mitotic exit. Nature Cell Biol 11, 1363-9(2009).
16. Anand, S., Penrhyn-Lowe, S. & Venkitaraman, A.R. AURORA-A amplification overrides the mitotic spindleassembly checkpoint, inducing resistance to Taxol. Cancer Cell 3, 51-62 (2003).
Technologies to identify and therapeutically target protein-protein interactions
17. Narvaez, A. J., Ber, S., Crooks, A., Emery, A., Hardwick, B., Guarino-Almeida, E., Huggins, D. J., Perera,D., Roberts-Thomson, M., Azzarelli, R., Hood, F. E., Prior, I. A., Walker, D. W., Boyce, R., Boyle, R. G.,Barker, S. P., Torrance, C. J., McKenzie, G. J. & Venkitaraman, A. R. Modulating Protein-Protein
Interactions of the Mitotic Polo-Like Kinases to Target Mutant Kras. Cell Chem Biol 24, 1-12. (2017).
18. Emery, A., Hardwick, B.S., Crooks, A.T., Milech, N., Watt, P.M., Mithra, C., Kumar, V., Giridharan, S.,
Sadasivam, G., Mathivanan, S., Sudhakar, S., Bairy, S., Bharatham, K., Hurakadli, M.A., Prasad, T.K.,
Kamariah, N., Muellner, M., Coelho, M., Torrance, C.J., McKenzie, G.J., Venkitaraman, A.R. Target
identification for small-molecule discovery in the FOXO3a tumor-suppressor pathway using a biodiverse
peptide library. Cell Chem Biol 28, 1602-15. (2021).
The B cell antigen receptor and its developmental diversification by genome rearrangement
19. Venkitaraman, A.R., Williams, G.T., Dariavach, P. & Neuberger, M.S. The B-cell antigen receptor of the
five immunoglobulin classes. Nature 352, 777-81 (1991).
20. Corcoran, A.E., Riddell, A., Krooshoop, D. & Venkitaraman, A.R. Impaired immunoglobulin gene
rearrangement in mice lacking the IL-7 receptor. Nature 391, 904-7 (1998).