The Pomerantz lab is a chemical biology group at the University of Minnesota. Our interdisciplinary research uses a wide range of techniques including organic synthesis, bioanalytical chemistry, biochemistry and molecular biology for studying the function of transcription factors involved in disease. Our primary goal is to discover small molecules which we can synthesize in the laboratory to modulate the function of protein-protein interactions involved in transcription, with the ultimate goal of developing new chemical probes for understanding the biology of these proteins.
Our Research: Our overarching goal is to discover new ways to inhibit protein-protein interactions (PPIs) involved in transcription. Our research seeks to understand the molecular level details of transcription factor-protein interactions and epigenetic complexes which control how our genetic information is expressed. At the same time, we use chemistry to design synthetic molecules that disrupt the dysregulated forms of PPI communication to further understand the underlying biology and treat disease. We apply NMR and MRI, to visualize biomolecular interactions, and use small molecules that we synthesize in the laboratory to perturb the protein function. Students and postdocs working in this area are exposed to broad training in organic synthesis, protein biochemistry, fragment-based drug design and additional applied biophysics techniques to validate our 19F NMR approach.
Given that transcription factors represent a major class of potential drug targets and the demand for structural methods to characterize them, our biomolecular 19F NMR approach for transcription factor-PPIs could significantly increase the repertoire of new targets and open up new paths forward for small molecule discovery.
Congrats to Huda and Caroline on the publication of "New Design Rules for Developing Potent Cell-Active Inhibitors of the Nucleosome Remodeling Factor (NURF) via BPTF Bromodomain Inhibition" to the Journal of Medicinal Chemistry.
Their body of work provides a systematic structure-based design approach to generate some of the most potent inhibitors for the BPTF bromodomain. You can read more about their work here.
Congrats to Dr. Huarui Cui for successfully defending her thesis today titled “Development of Small Molecule Chemical Probes for BRD4,” a beautiful body of work developing selective inhibitors for this important anticancer and anti-inflammatory drug target. Huarui will depart later this month to start her postdoc at MIT with Prof. Angela Koehler.
Congrats to Anand Divakaran for successfully defending his dissertation titled "Development and Cellular Evaluation of Selective N-Terminal BET Bromodomain Inhibitors." Anand was co-advised with Dan Harki. He will be departing shortly to start a postdoc with Dan Nomura at UC Berkeley.
Congratulations to Caroline for the publication of "19F NMR viewed through two different lenses: ligand-observed and protein-observed 19F NMR applications for fragment-based drug discovery" to RSC Chemical Biology.
This review is a deep dive into 19F NMR in FBDD. You can read the full review here.