The Chakraborty laboratory studies chromatin biology in the context of dysregulated activity of oxygen-dependent enzymes (or dioxygenases), such as the JumonjiC-family histone demethylases (or KDMs). The physiological implications of dioxygenase dysfunction are relevant in kidney cancer, where these enzymes are often mutated; and also more broadly in the context of hypoxia, where some of these enzymes can be inactivated due to inadequate oxygen availability.
The 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, the laboratory is currently focused on the following major questions:
- Defining the Relevance Epigenetic Dysfunction to Identify Actionable Targets in Kidney Cancer; and
- Defining the Contribution of Oxygen-sensing Dioxygenases in Cell State and Differentiation
By relying on a spectrum of biological techniques, including basic biochemistry, high-throughput genomic and chemical screens, metabolomics, and epigenomics analyses, the Chakraborty laboratory hopes to define the biological mechanisms underlying pathologies triggered by dioxygenase dysfunction, and identify means to redress these pathologies.