Studying Structure-Function Relationships in Epigenetic and Proteostasis Mechanisms and Their Therapeutic Targeting in Cancers
The Chandrasekharan Lab’s focus is to understand the regulation and functions of epigenetic histone modifications and protein homeostasis (proteostasis) mechanisms during gene regulation and genome maintenance, and their therapeutic targeting in cancers.
Our current interests include the following:
- Uncover the molecular mechanisms involved in the crosstalk between histone H2B ubiquitination and histone H3 lysine-4 and lysine-79 methylation
- Understand the intricacies of ubiquitin-conjugation mechanisms involved in protein turnover
- Determine whether the epigenetic or ubiquitin-conjugating enzymes involved in the crosstalk act as molecular vulnerabilities in cancers
Enzymes and regulatory factors involved in this evolutionarily conserved trans-histone crosstalk play important roles both in normal development and in cancer-related processes. We use yeast and mammalian model systems, and employ both classical and modern, biochemical, biophysical, structural, genetic, and genomics-based approaches in order to understand various aspects of epigenetics/chromatin biology and protein biology. We also extend our fundamental studies to design and test novel small molecule inhibitors or devise new therapeutic strategies to effectively target misregulated epigenetic or proteostasis mechanisms in cancers.