A fundamental understanding of the mechanisms underlying human diseases is essential to discover new ways to detect and manage them. It is this perspective that drives Professor Ashok Venkitaraman’s desire to develop new strategies to intercept cancer at the earliest stages possible. His work is motivated by the idea that early cancer interception before the disease reaches an advanced stage promises to revolutionise its treatment, and even delay or prevent its onset.
Prof Venkitaraman is widely recognised for discovering how an important class of cancer-suppressing genes, exemplified by the hereditary breast cancer gene, BRCA2, guards the integrity of the human genome to prevent carcinogenesis. His research has shed light on the molecules and mechanisms that monitor the copying and repair of our DNA, and how aberrations in these processes can cause cancer.
His fundamental discoveries have led Prof Venkitaraman to innovate technologies that accelerate the development of next-generation therapies to intercept cancer. These include new technology platforms to identify and validate therapeutic targets in complex pathways, to modulate enzyme activity via regulatory protein-protein interactions, and to interrogate cellular signaling pathways using new light microscopy-based tools. He has serially ‘spun out’ these new technologies to industry, where they are now being deployed in partnership with major pharmaceutical companies to develop new drugs.
Prof Venkitaraman’s research at the Cancer Science Institute of Singapore builds on these foundational discoveries. His work has begun to reveal how chemical signals from our environment, diet and metabolism can affect the function of cancer-suppressing genes like BRCA2, deepening our fundamental understanding of the origins of cancer, and opening new avenues for its treatment and prevention. He is devising new tools to target proteins and nucleic acids like RNA in diseased cells to accelerate better cancer treatment outcomes.
Prof Venkitaraman has been elected to the Academy of Medical Sciences, London, and the European EMBO academy, Heidelberg, in recognition of his contributions.
Uncovering vital insights into the distinct effects of BRCA2 mutations on breast tissue cells, shedding light on early breast cancer development in people with BRCA2 mutations
Ketogenic diets delay tumour growth but accelerate cachexia, a wasting syndrome, an unintended side effect that could cause death
Heatrich-BS assay, a novel low-cost and highly sensitive blood test for regular cancer monitoring
Emery, A., Hardwick, B. S., Crooks, A. T., Milech, N., Watt, P. M., Mithra, C., ... & Venkitaraman, A. R. (2021). Target identification for small-molecule discovery in the FOXO3a tumor-suppressor pathway using a biodiverse peptide library. Cell chemical biology, 28 (11), 1602-1615.
Tan, S. L. W., Chadha, S., Liu, Y., Gabasova, E., Perera, D., Ahmed, K., ... & Venkitaraman, A. R. (2017). A class of environmental and endogenous toxins induces BRCA2 haploinsufficiency and genome instability. Cell, 169 (6), 1105-1118.
Jeyasekharan, A. D., Liu, Y., Hattori, H., Pisupati, V., Jonsdottir, A. B., Rajendra, E., ... & Venkitaraman, A. R. (2013). A cancer-associated BRCA2 mutation reveals masked nuclear export signals controlling localization. Nature structural & molecular biology, 20 (10), 1191-1198.
Skoulidis, F., Cassidy, L. D., Pisupati, V., Jonasson, J. G., Bjarnason, H., Eyfjord, J. E., ... & Venkitaraman, A. R. (2010). Germline Brca2 heterozygosity promotes KrasG12D-driven carcinogenesis in a murine model of familial pancreatic cancer. Cancer cell, 18 (5), 499-509.
Ayoub, N., Jeyasekharan, A. D., Bernal, J. A., & Venkitaraman, A. R. (2008). HP1-β mobilization promotes chromatin changes that initiate the DNA damage response. Nature, 453 (7195), 682-686.
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