High Throughput Screening

Rational Drug Design

Chemical Tools to Study Epigenetic Mechanism and Reprogram Gene Regulation

We will use high-throughput cell-based phenotypic screening to discover leads as ligands and inhibitors of proteins, disruptors, and the molecular glue of protein-protein interactions. We will also use computer-aided virtual screening, including pharmacophore-based, MD simulation-based, and NMR-aided fragment screening, and phenotypic screening to obtain leads as ligands of proteins of interest. Binding interactions will be further validated using biochemical and biophysical methods, including luciferase assays, TR-FRET assays, SPR, CETSA, and MD simulations.

We will conduct a medicinal chemistry campaign to optimize the ADME (Absorption, Distribution, Metabolism, and Excretion) and toxicity profiles of our lead compounds. By integrating rational with computer-assisted drug design (CADD) techniques and collaborating closely with structural biologists, we aim to refine our drug candidates for maximum efficacy and safety. The optimized molecules will be evaluated in relevant disease animal models as we prepare for preclinical development.

We will develop chemical probes and use them with genetic tools, including transcriptomic, ChIP-seq, and proteomic approaches, to understand epigenetic processes and discover drug targets that exploit epigenetic modifiers. My research also explores chemically induced proximity (CIP) as an innovative strategy to reprogram cellular functions, including chromatin architecture, transcriptional regulation, and signaling pathways. These approaches will provide a versatile framework to investigate epigenetic mechanisms in situ and establish the foundation for developing proximity-based therapeutics across diverse diseases