David Nie, PhD
Rewiring Epigenetics Using Proximity-Inducing Drugs for Cancer Therapeutics
Abstract
Many cancers exhibit dysregulation of a protein called NSD3, which is a significant driver and amplifier of cancerous growth. NSD3 controls how DNA is packaged, and when it is dysregulated, it keeps certain cancer-driving genes turned on. Rather than inhibiting or degrading NSD3, as traditional drug design strategies do, my project takes an innovative approach of redirecting NSD3 activity to turn on genes that normally suppress tumor growth. I aim to design proximity-inducing drugs: molecules that can recruit NSD3 to silenced tumor-suppressor genes. By physically bringing NSD3 into proximity with these “off” genes, NSD3 can flip them back “on” and reactivate the cancer-fighting abilities. Since our strategy relies on NSD3 activity, it is theoretically much more selective towards intended cancers due to their NSD3 dysregulation, while sparing normal or NSD3-low cells. This work provides a proof of concept for this drug modality and can pave the way for more effective cancer treatments.
It’s an honor to be selected as a PhRMA Foundation awardee. This recognition is a powerful catalyst for my research on the next generation of anti-cancer therapeutics and reinforces my commitment to advancing the frontiers of cancer drug discovery.
