Ashok Venkitaraman

Ashok Venkitaraman is a British cancer researcher of Indian origin. He is the Director of the Cancer Science Institute of Singapore, a Distinguished Professor of Medicine at the National University of Singapore, and Program Director at A*STAR, Singapore.[1] From 1998 to 2020, he was the inaugural holder of the Ursula Zoellner Professorship of Cancer Research at the University of Cambridge, a Professorial Fellow at Pembroke College, Cambridge, and from 2006 to 2019, was the Director of the Medical Research Council Cancer Unit[2][3][4]

Ashok Venkitaraman
Alma mater
Awards
Websitehttps://www.csi.nus.edu.sg/web/ashok-venkitaraman/ https://www.mrc-cu.cam.ac.uk/research/ashok-venkitaraman-folder
Academic career
FieldsImmunology, Oncology, Molecular biology, Chemical biology
InstitutionsCancer Science Institute of Singapore

National University of Singapore A*STAR Singapore

Medical Research Council (MRC) Cancer Unit University of Cambridge

MRC Laboratory of Molecular Biology
ThesisThe regulation of MHC class 2 gene expression by tumours of the B lymphocyte lineage
Doctoral advisorMarc Feldmann

Biography

Venkitaraman learnt and practiced medicine at the Christian Medical College, Vellore, India, before earning his PhD at University College London supervised by Sir Marc Feldman.[2][5][3] He was awarded in 1988 a Beit Memorial Fellowship to work with Michael Neuberger at the MRC Laboratory of Molecular Biology in Cambridge, before becoming a member of its research faculty in 1991. In 1998, he was elected as the first holder of the Ursula Zoellner Professorship[6]

Venkitaraman joined the MRC Cancer Unit in 2000, becoming its co-director with Ron Laskey in 2006, and its Director in 2010. During his directorship, he developed a distinctive scientific mission for the MRC Cancer Unit focused on early intervention in cancer, through research that advances understanding of early steps in carcinogenesis, and utilizes this new knowledge for the early detection of cancer, and improvements in therapy or prevention.

In 2020, Venkitaraman took up joint appointments as the Director of the Cancer Science Institute of Singapore, Distinguished Professor of Medicine at the National University of Singapore, and Program Director at A*STAR, Singapore.

Research

Venkitaraman is widely recognised for his contributions to understanding the genetics and biology of human cancer, particularly in elucidating the impact of genome instability on carcinogenesis and cancer therapy. He is best known for discovering how mutations affecting the breast cancer gene, BRCA2, and related proteins cause genome instability to trigger carcinogenesis.[7][8] His work has helped to explain why carriers of BRCA2 mutations develop cancer,[7][8] and has provided the scientific foundations for new cancer therapies by illuminating fundamental cellular mechanisms that control genome repair, duplication and segregation.[7][8]

Venkitaraman was amongst the first to discover that the breast cancer gene, BRCA2, is essential to maintain the integrity of the genome when cells divide.[9] He and his colleagues soon uncovered that BRCA2 enables cells to repair DNA breakage in an error-free manner by precisely controlling the assembly of the RAD51 recombination enzyme on its DNA substrates,[9][10][11] and revealed the structural mechanism underlying this process.[9][12] He subsequently discovered that BRCA2 is vital to prevent DNA breakage when genome replication becomes blocked or stalled,[13] helping to explain why BRCA2-deficient cells spontaneously exhibit genome instability during cell division, and why BRCA2-deficient cancers become highly sensitive to drugs that block genome replication by causing DNA cross-links or gaps.[8] These discoveries have laid a scientific foundation for the development of new treatments for cancers arising in patients who carry BRCA2 mutations, and also provided a conceptual framework for understanding other human genetic diseases in which genome instability is connected with predisposition to cancer.[8]

Venkitaraman's research continues to unveil new ways in which BRCA2 and related genes work to preserve genome integrity, and to explain how patients who carry BRCA2 mutations become more susceptible to early-onset cancers. He and his colleagues have recently discovered that cells carrying a single copy of mutant BRCA2 become more susceptible to the mutagenic effects of aldehydes, a class of chemicals found pervasively in the environment and generated in cells through metabolic reactions.[14]

Venkitaraman has developed technologies that help to identify and validate new targets for next-generation medicines against cancer and other diseases. Work in his laboratory laid the scientific foundations for the development of “protein interference” at PhoreMost,[15] which he co-founded with Chris Torrance and Grahame Mckenzie. This new technology is now being widely applied in collaborations with major pharmaceutical companies.[16][17] Venkitaraman's laboratory has also devised new approaches to target cellular pathways initiated by enzymes like protein kinases. For example, they have selectively interrupted intracellular signaling by blocking the molecular recognition of protein phosphorylation using small-molecule chemical tools,[18] now being pursued by industry for anti-cancer therapy. He has worked extensively with UK industry to develop new medicines. Having served for many years on the scientific advisory boards of companies such as Astex Therapeutics and Cambridge Antibody Technology/MedImmune, he currently holds appointments with Sentinel Oncology and PhoreMost.

Venkitaraman has worked for many years to promote biomedical research in India. He leads a collaborative research initiative with the National Center for Biological Sciences and inStem in Bangalore,[19][20] in which new technology is being applied to help develop drugs against cancer and other diseases. He has established an initiative for biological systems engineering at the Indian Institute of Technology-Madras, where he holds the Mehta Foundation Visiting Professorship.

Awards and honours
  • In 2001, Venkitaraman was elected a Fellow of the Academy of Medical Sciences, one of the four national academies of the United Kingdom.
  • In 2004, he was elected a Member of the  European Molecular Biology Organization (EMBO), awarded for research excellence and outstanding achievements in the life sciences.
  • Venkitaraman was awarded in 2017 the Basser Global Prize in recognition of his discoveries concerning the breast cancer gene BRCA2.[21]

References
  1. "Prominent cancer researcher Ashok Venkitaraman to head Cancer Science Institute of Singapore at NUS".
  2. "MRC Cancer Unit Professor Ashok Venkitaraman biography".
  3. "Venkitaraman, Prof. Ashok. UK WHOS WHO. 2017". doi:10.1093/ww/9780199540884.013.41050. ISBN 978-0-19-954088-4.
  4. "Fellows and College Officers, Pembroke College Cambridge".
  5. Venkitaraman, Ashok Ramakrishnan (1989). Venkitaraman, Ashok (1989). "The regulation of MHC class 2 gene expression by tumours of the B lymphocyte lineage" (Ph.D).
  6. "University of Cambridge Reporter University Officers".
  7. Venkitaraman, A. R. (January 2002). "Cancer Susceptibility and the Functions of BRCA1 and BRCA2". Cell. 108 (2): 171–182. doi:10.1016/s0092-8674(02)00615-3. PMID 11832208. S2CID 10397442.
  8. Venkitaraman, A. R. (27 March 2014). "Cancer Suppression by the Chromosome Custodians, BRCA1 and BRCA2". Science. 343 (6178): 1470–1475. Bibcode:2014Sci...343.1470V. doi:10.1126/science.1252230. PMID 24675954. S2CID 206556058.
  9. Patel, K. J.; Yu, V. P. C. C.; Lee, H.; Corcoran, A.; Thistlethwaite, F. C.; Evans, M. J.; Colledge, W. H.; Friedman, L. S.; Ponder, B. A. J.; Venkitaraman, A. R. (February 1998). "Involvement of Brca2 in DNA Repair". Molecular Cell. 1 (3): 347–357. doi:10.1016/s1097-2765(00)80035-0. PMID 9660919.
  10. "The Fight Against Cancer - University of Cambridge news story".
  11. Shivji, M. K. K.; Mukund, S. R.; Rajendra, E.; Chen, S.; Short, J. M.; Savill, J.; Klenerman, D.; Venkitaraman, A. R. (23 July 2009). "The BRC repeats of human BRCA2 differentially regulate RAD51 binding on single- versus double-stranded DNA to stimulate strand exchange". Proceedings of the National Academy of Sciences. 106 (32): 13254–13259. Bibcode:2009PNAS..10613254S. doi:10.1073/pnas.0906208106. PMC 2714763. PMID 19628690.
  12. Short, J. M.; Liu, Y.; Chen, S.; Soni, N.; Madhusudhan, M. S.; Shivji, M. K. K.; Venkitaraman, A. R. (5 September 2016). "High-resolution structure of the presynaptic RAD51 filament on single-stranded DNA by electron cryo-microscopy". Nucleic Acids Research. 44 (19): 9017–9030. doi:10.1093/nar/gkw783. PMC 5100573. PMID 27596592.
  13. Lomonosov, M.; Anand, S.; Sangrithi, M.; Davies, R.; Venkitaraman, A. R. (15 December 2003). "Stabilization of stalled DNA replication forks by the BRCA2 breast cancer susceptibility protein". Genes & Development. 17 (24): 3017–22. doi:10.1101/gad.279003. PMC 305253. PMID 14681210.
  14. 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. (June 2017). "A Class of Environmental and Endogenous Toxins Induces BRCA2 Haploinsufficiency and Genome Instability". Cell. 169 (6): 1105–1118.e15. doi:10.1016/j.cell.2017.05.010. PMC 5457488. PMID 28575672.
  15. "Cambridge University Enterprise announcement".
  16. "PhoreMost and Boehringer Ingelheim enter multi-project drug discovery collaboration - Drug Discovery Today". www.drugdiscoverytoday.com.
  17. "Otsuka enters multi-project drug discovery collaboration with PhoreMost Limited｜News Releases". Otsuka Pharmaceutical Co., Ltd.
  18. 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. (August 2017). "Modulating Protein-Protein Interactions of the Mitotic Polo-like Kinases to Target Mutant KRAS". Cell Chemical Biology. 24 (8): 1017–1028.e7. doi:10.1016/j.chembiol.2017.07.009. PMC 5563081. PMID 28807782.
  19. "Department of Biotechnology, Cambridge varsity in research venture". @businessline. 14 September 2012.
  20. "Breakthrough medical research collaboration receives Indian government funding boost". University of Cambridge. 5 October 2012.
  21. "Penn's Basser Center for BRCA Names Cambridge Cancer Researcher Ashok Venkitaraman Winner of 2017 Basser Global Prize".
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