Appointment(s)
Director, Cancer Science Institute of Singapore
Distinguished Professor of Medicine, Yong Loo Lin School of Medicine, National University of Singapore
Director, National University of Singapore Centre for Cancer Research
Degree(s)
Doctor of Philosophy
B of Med, B of Surg
Biography
My laboratory aspires to understand the mechanisms underlying human cancer susceptibility, in order to find innovative ways to intercept cancer early in its evolution. Genome instability, a hallmark and driver of cancer evolution, arises early in carcinogenesis, through the failure of mechanisms that normally safeguard genome integrity. We study these mechanisms to understand how their malfunction leads to cancer, and have devised powerful new technologies to translate this knowledge to clinical application for early cancer detection and treatment. One major interest is in the ‘breast cancer gene’ BRCA2, whose vital role as a genome guardian we were amongst the first to discover.
Research Areas/Research Interest
- BRCA2
- Cancer
- Translational
- Innovation
- Therapeutic
Lab Description
My laboratory aspires to understand the mechanisms underlying human cancer susceptibility, in order to find innovative ways to intercept cancer early in its evolution. To understand cancer susceptibility, we use inherited mutations in the ‘breast cancer gene’ BRCA2 as a powerful model system. BRCA2 mutation carriers are highly susceptible to cancer. My lab was amongst the first to discover that BRCA2 suppresses cancer by guarding genome integrity, and to establish scientific foundations for the targeted therapy of BRCA-deficient cancers. At CSI, we aim to identify structural and biophysical mechanisms that underlie the functions of BRCA2, to better understand how these functions are perturbed by cancer-causing mutations in BRCA2 and associated factors. To develop innovative therapeutic approaches, my lab has devised powerful new technology platforms to identify and validate therapeutic targets in complex pathways, to modulate enzyme activity outwith the catalytic site via regulatory protein-protein interactions (allo-targeting), and to interrogate cellular signaling pathways using new tools in light microscopy. These technology innovations have led to serial Cambridge University spin-out companies, and close interactions with industry and venture capital. At CSI, we deploy our new technologies to find ways to delay or prevent the evolution of cancers in high-risk individuals in close collaboration with Ashok’s laboratory at A*STAR. Our multi-disciplinary research bridges from bench to bedside, subtending a wide range of techniques from molecular cell biology to single-cell/single-molecule imaging to structural biology, biophysics and chemistry.
BRCA2 Regulates Transcription Elongation by RNA Polymerase II to Prevent R-Loop Accumulation
Shivji, M.K., Renaudin, X., Williams, C., Venkitaraman, A.R.
A Class of Environmental and Endogenous Toxins Induces BRCA2 Haploinsufficiency and Genome Instability
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.
A cancer-associated BRCA2 mutation reveals masked nuclear export signals controlling localization
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.
Germline Brca2 Heterozygosity Promotes KrasG12D -Driven carcinogenesis in a murine model of familial pancreatic cancer
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.
HP1-β mobilization promotes chromatin changes that initiate the DNA damage response
Ayoub, N., Jeyasekharan, A.D., Bernal, J.A. & Venkitaraman, A.R.
Abnormal cytokinesis in cells deficient in the breast cancer susceptibility protein BRCA2
Daniels, M.J., Wang, Y., Lee, M. & Venkitaraman, A.R.
Insights into DNA recombination from the structure of a RAD51-BRCA2 complex
Pellegrini, L., Yu, D.S., Lo, T., Anand, S., Lee, M., Blundell, T.L. & Venkitaraman, A.R.
Pulsatile MAPK Signaling Modulates p53 Activity to Control Cell Fate Decisions at the G2 Checkpoint for DNA Damage
De S, Campbell C, Venkitaraman AR, Esposito A
Modulating Protein-Protein Interactions of the Mitotic Polo-like Kinases to Target Mutant KRAS
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.
Homeostatic control of polo-like kinase-1 engenders non-genetic heterogeneity in G2 checkpoint fidelity and timing
Liang, H., Esposito, A., De, S., Ber, S., Collin, P., Surana, U. & Venkitaraman, A.R.
