F. Michael Hoffmann

Research Description

For my first sixteen years on the faculty at UW (1984-2000), I used Drosophila genetics to study two highly conserved genes, the Abl proto-oncogene and a TGF-beta superfamily member growth factor, Dpp. Beginning in 2000, I transitioned my research from classical genetics to chemical genetic approaches. Over the past seventeen years my research activities, funding and publications have focused on chemical biology and drug discovery. I have had leadership roles in the Department of Oncology, the University of Wisconsin Carbone Cancer Center (UWCCC) Experimental Therapeutics Program, the Small Molecule Screening Facility and the Medicinal Chemistry Center. I have participated regularly in NIH review panels focused on high throughput screening, drug discovery and core facilities. Previous research in my laboratory funded by NIH, JDRF and MDA focused on chemical biology investigations of TGF-beta signal transduction, specifically on Smad protein-protein interactions. The research in my laboratory identified small peptide inhibitors of several Smad protein interactions that perturbed the signaling pathway in cells. We also published an extensive mutational analysis of the Smad3 amino acids mediating specific protein-protein interactions. Since 2011, I have applied my interests in drug discovery to multiple collaborations with UW colleagues. I am the co-PI for the discovery core on the UW Center for Excellence in Translational Research U19 “Antimicrobial Drug Discovery from Coevolved Symbiotic Communities”. I currently work with 13 staff scientists in my role as co-leader of the Drug Development Core. This core encompasses the full spectrum of medicinal chemistry including HTS discovery, synthetic chemistry, computational chemistry, analytical chemistry and pharmacology. The DDC supports UW scientists in their efforts to discover and evaluate new drugs. Some examples of unique DDC services include sourcing and assaying chemical libraries of over 450,000 drug-like chemicals; computational chemistry for in silico virtual screening and lead optimization design; chemical informatics to identify and prioritize compounds; chemical synthesis of potent, selective, and pharmacologically viable compounds; and analytical chemistry to support UWCCC clinical trials with pharmacokinetic and pharmcodynamic assays.  A current focus is on computationally-aided drug discovery as co-PI on the interdisciplinary UW2020 program “An Adaptive Computational Pipeline to Accelerate Drug Discovery”.