Member, Genitourinary Malignancies Research Center
Location: Cleveland Clinic Main Campus
How do we sense and respond to a lack of adequate oxygen and why does it matter? While we all know the physiological responses (think gasping or panting) typically associated with insufficient oxygen availability; our cells are equally hardwired at a molecular level to respond to this adversity. We do so by employing a uniquely evolved set of proteins that function only in the presence of oxygen. Loss of oxygen switches off these proteins and in the process triggers a slew of downstream consequences, including changes in the levels of numerous genes and metabolites. Together, these changes allow oxygen-deficient cells to adapt and survive in the face of what would otherwise be a catastrophic event. Unfortunately, what were processes that we originally evolved for survival, are also hijacked by cancer cells, especially as they become more aggressive and outgrow their oxygen supply. We propose that studying these molecular responses could reveal the central schemes that oxygen-deprived cancer cells employ for survival. Blocking these processes in cancer cells, in turn, could prove lethal - and exploited for therapeutic purposes. Our laboratory, therefore, studies the proteins and processes involved in sensing and responding to oxygen loss, with the hope that this knowledge can ultimately identify creative ways to disarm what is a hostile takeover.
Our laboratory studies chromatin biology in the context of dysregulated activity of oxygen-dependent enzymes (or dioxygenase), such as the JumonjiC-family histone demethylases (or KDMs). The physiological implications of dioxygenase dysfunction is relevant in kidney cancer, where these enzymes are often mutated; and also more broadly in the context of hypoxic tumors, where these enzymes can be inactivated due to inadequate oxygen availability. Our laboratory’s central theme is to exploit dioxygenase dysfunction—and the resulting epigenetic anomalies—to identify targetable vulnerabilities in the context of cancer.
To address these goals, our laboratory is currently focused on three major questions:
View publications for Abhishek Chakraborty, PhD
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Dr. Chakraborty will study one candidate oncogene’s contributions to kidney cancer, looking specifically at the role it may play in cancer cell metabolism, thanks to a new award from the Department of Defense, his first federal research grant.