Studying Structure-Function Relationships in Epigenetic and Proteostasis Mechanisms and Their Therapeutic Targeting in Cancers 

The Chandrasekharan Lab investigates how epigenetic histone modifications and protein homeostasis (proteostasis) mechanisms regulate gene expression and genome maintenance, and how these pathways can be targeted therapeutically in cancer.

Our current research focuses on:

• Uncover the molecular mechanisms underlying the dynamic regulation and functions of histone ubiquitination, methylation, and acetylation
• Understand the intricacies of ubiquitin-conjugation mechanisms involved in protein turnover
• Determine whether epigenetic or ubiquitin-conjugating enzymes represent molecular vulnerabilities in cancers, particularly leukemias and lymphomas

The enzymes and regulatory factors that mediate epigenetic/chromatin modifications and proteostasis are essential for normal development and are frequently dysregulated in cancer. To dissect their functions, we use both yeast and mammalian model systems and integrate classical and modern biochemical, biophysical, structural, genetic, and genomics-based approaches to investigate epigenetics/chromatin biology and protein biology.

Building on these mechanistic insights, we also work to design and test novel small-molecule inhibitors and to develop new therapeutic strategies aimed at correcting misregulated epigenetic and proteostasis pathways in cancer.