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Ashok VENKITARAMAN
Cancer biology & genetics, immunology, therapeutics discovery
MBBS, PhD, FMedSci
SUMMARY
Ashok VENKITARAMAN is a Research Director at IMCB, Distinguished Professor of Medicine at the National University of Singapore, Director of the Cancer Science Institute of Singapore, and Executive Director for the National Initiative on RNA Biology & Its Applications (NIRBA). He was previously the Ursula Zoellner Professor of Cancer Research at the University of Cambridge from 1998-2020, Director of the Medical Research Council (MRC) Cancer Unit in Cambridge from 2006-2019, and remains a fellow of Pembroke College, Cambridge. Ashok was inducted as a Fellow of the Academy of Medical Sciences, London in 2001, and as a member of the EMBO academy, Heidelberg, in 2004. He currently serves on the advisory board of Cell.
Ashok’s groundbreaking research has illuminated the mechanism of a class of genes frequently inactivated in human cancers, and empowered targeted cancer therapy. He is recognized for discovering the tumour suppressive functions of the hereditary breast cancer gene, BRCA2, and showing how its inactivation causes cancer. He has invented and commercialized technologies to accelerate drug discovery, founding serial spin-out companies including PhoreMost. Ashok has served (and continues to serve) on multiple academic and pharma scientific advisory boards, including that of Chugai Pharmaceuticals in Japan (a member of the Roche Group), and has contributed to national agencies that formulate scientific policy.
Ashok has mentored many leading clinicians and scientists as postdoctoral fellows or PhD students in his laboratory, including Prof. Ketan Patel (Director, Weatherall Institute of Molecular Medicine, Oxford), Prof. Nabieh Ayoub (Technion, Israel), Prof. David Yu (Jerome Landry Chair of Cancer Biology, Winship Cancer Center), Prof. Matthew Garnett (Sanger Institute, Cambridge), Prof. Hyunsook Lee (Seoul National University, Korea), Prof. Vihanda Wickramasinghe (Walter & Eliza Hall Institute, Melbourne), Dr. Ana Julia Narvaez (Director of Translational Biology, Moderna Therapeutics), A/Prof Ferdinandos Skoulidis (MD Anderson Cancer Center), A/Prof Xinyi Su (Executive Director, IMCB, A*STAR), and Asst. Prof. Anand Jeyasekharan (Principal Investigator, CSI, Asst. Director of Research, NCIS).
- 2024: National Medical Research Council Open Fund-Large Collaborative Grant (NMRC-OF-LCG)
- 2024: Ministry of Education (MOE) Academic Research Fund (AcRF)
- 2023: A*STAR Industry Alignment- Pre-Positioning Grant (IAF-PP)
- 2023: Gray Foundation Team Science Award
- 2022: Ministry of Education (MOE) Academic Research Fund (AcRF)
- 2021: A*STAR Industry Alignment- Pre-Positioning Grant (IAF-PP)
RESEARCH
My lab’s overall goal is to understand the mechanisms underlying susceptibility to cancer, and to exploit this knowledge in innovative approaches for early clinical intervention in the commonest human cancers. We focus on scientific questions rather than methodological approaches, and deploy or invent new technologies where required to address such questions.
To understand cancer susceptibility, we use inherited mutations in the BRCA2 gene as a powerful model system. My lab was amongst the first to discover the biological functions of BRCA2 in genome maintenance underlying its role as a tumour suppressor, to lay the foundations for the targeted therapy of BRCA-deficient cancers, and to reveal metabolic mechanisms that ‘bypass’ tumour suppression to initiate carcinogenesis.
To develop innovative approaches for clinical intervention, my lab has devised powerful new technology platforms to identify and validate therapeutic targets in complex pathways (Protein-interference), to modulate enzyme activity using small-molecule ligands outwith the catalytic site via regulatory protein-protein interactions (allo-targeting), and to interrogate cellular signaling pathways using new tools in light microscopy (e.g. hyper-dimensional imaging microscopy). These technology innovations have led to serial Cambridge University spin-out companies (PhoreMost Ltd., Sentinel Oncology Ltd.), which have reached clinical impact through ongoing clinical trials of new drugs.
Our ongoing research has revealed metabolic triggers and environmental cues that modulate early steps in carcinogenesis associated with common metabolic disorders like diabetes, morbid obesity or metabolic-dysfunction associated steatohepatitis (MASH). Their underlying mechanisms are being studied to elicit new approaches for health impact in early therapeutic or preventive interventions, through translation in proof-of-concept clinical studies.
- A glycolytic metabolite bypasses ‘‘two-hit’’ tumor suppression by BRCA2.
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. (2024)
Cell 187, 2269–2287 - A transcriptional response to replication stress selectively expands a subset of Brca2-mutant mammary epithelial cells.
Najafabadi MG, Gray GK, Kong LR, Gupta K, Perera D, Naylor H, Brugge JS, Venkitaraman A.R.*, Shehata M*. (2023)
Nature Comm 14(1):5206
(* Joint senior author) - Ketogenic diet promotes tumor ferroptosis but induces relative corticosterone deficiency that accelerates cachexia.
Ferrer M, Mourikis N, Davidson EE, Kleeman SO, Zaccaria M, Habel J, Rubino R, Gao Q, Flint TR, Young L, Connell CM, Lukey MJ, Goncalves MD, White EP, Venkitaraman AR, Janowitz T. (2023)
Cell Metabolism 35(7):1147-1162. - Domain-specific p53 mutants activate EGFR by distinct mechanisms exposing tissue-independent therapeutic vulnerabilities.
Ho TLF, Lee MY, Goh HC, Ng GYN, Lee JJH, Kannan S, Lim YT, Zhao T, Lim EKH, Phua CZJ, Lee YF, Lim RYX, Ng PJH, Yuan J, Chan DKH, Lieske B, Chong CS, Lee KC, Lum J, Cheong WK, Yeoh KG, Tan KK, Sobota RM, Verma CS, Lane DP, Tam WL, Venkitaraman A.R. (2023)
Nature Comm 14(1):1726. - Target identification for small-molecule discovery in the FOXO3a tumor-suppressor pathway using a biodiverse peptide library.
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. (2021)
Cell Chem Biol 28, 1602-15. - A Class of Environmental and Endogenous Toxins Induces BRCA2 Haploinsufficiency and Genome Instability.
Tan SLW, Chadha S, Liu Y, Gabasova E, Perera D, Ahmed K, Constantinou S, Renaudin X, Lee M, Aebersold R, Venkitaraman AR.
Cell. 2017 Jun 1;169(6):1105-1118.e15. doi: 10.1016/j.cell.2017.05.010
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