We are interested in understanding the mechanism of epigenetic regulators that control cell growth, differentiation, carcinogenesis and adaptation. Through use of the chemical probes to target the epigenetic regulators we are investigating the cellular functions of these proteins and their potential to become therapeutic targets in such diseases as cancer. Our work focuses on protein lysine and arginine methyltransferases involved in transcription, genome stability, RNA metabolism and variety of cell processes determined by the substrates of these cellular enzymes. The PRMT, arginine methyltransferase, family has especially wide scope of substrates ranging from histones to signaling molecules, enzymes and structural proteins. Through multidisciplinary research that includes cell and chemical biology, protein structural biology and many collaborative studies with colleagues across industry and academia, the SGC chemical probes project has generated several probes for various PRMTs. We are currently using the chemical probes to explore the cellular pathways that are controlled by PRMT enzymes in especially poor prognosis acute myeloid leukemia patient cells. The long term patient leukemia cell cultures developed in our group enable us to investigate the cancer cell growth, drug resistance and self-renewal capacity.

Epigenetics and chromatin architecture regulators

Epigenetics and chromatin architecture regulators
	Epigenetics is about how the DNA code is regulated. Proteins that bind/modify DNA and histones play essential roles in cell identity determination, transcription, and genome maintenance. They are often responsible for diseases such as cancer or uncontrolled inflammation. We are studying how epigenetic proteins regulate normal cell processes and how these are subverted in disease.

Chemical probes as tools for cancer target discovery

To study epigenetic modifier proteins, we need genetic and pharmacological tools. Chemical probe compounds that potently and selectively inhibit or degrade the target proteins in cells provide tools for modulating activating/repressing histone marks and other cellular signaling pathways. By discovering and using chemical probes, we expand our understanding of the protein function and its therapeutic utility to establish a biological rationale in cancer therapy.    For more information please see Group Research and Members tab above.

Link to Open Lab notebooks that features science community posts on our various projects https://openlabnotebooks.org/