Designing chemical tools to probe HAT1
Can we design a HAT1 inhibitor? Can we engineer proteogenomic tools to disrupt the HAT1 pathway?
We need better tools to study metabolic-epigenetic crosstalk. There have been few chemicals discovered that can modulate the HAT1 pathway. We are using principles of drug discovery, high-throughput screening, enzymology and cheminformatics to identify and develop bonafide HAT1 inhibitors. This is transdisciplinary work that bridges medicinal chemistry, protein biochemistry, and biophysical approaches like crystallography.
The VISTA immunoreceptor in triple-negative breast cancer
Epigenetic profiling allowed us to identify a novel immunoreceptor (VISTA) present on the surface of many human triple-negative breast cancers. VISTA bears homology to PD-L1 and is therefore a target of interest for cancer immunotherapy. We are characterizing how VISTA controls the growth of human breast cancers, specifically focused on molecular biology, biochemistry and cell biology. Finally, we are interested in human clinical trials that target VISTA.
Controlling the Epigenome
How are nucleosome made and can we control them?
Through our studies on HAT1 we have characterized histone control elements. These genome sequences control how and when nucleosomes are made, but the details remain murky. Using principles of retro-synthesis, genome design and reverse genetics we seek to de-construct and re-construct how histones are made and how they get assembled into chromatin. This should lead to new technologies to control the epigenome and new therapeutics to combat cancers.