UW madison
UW School of Medicine and Public Health
Carbone Cancer Center

F. Michael Hoffmann, Ph.D.

F. Michael Hoffmann
Romnes Professor of Oncology
Drug Development Shared Resource Faculty
Co-Leader - UW Carbone Cancer Center

B.S., 1973, Chemistry, Rensselaer Polytechnic Institute, NY
Ph.D., 1979, Biochemistry, Cornell University, NY
Postdoctoral research: Massachusetts Institute of Technology and Harvard University

Hoffmann - Drug Development Core

Office: 
7553 Wisconsin Institutes for Medical Research
Telephone: 
Office - (608) 263-2890
Email: 
fmhoffma@wisc.edu
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".

Selected Recent Publications: 

2018

Voter AF, Killoran MP, Ananiev GE, Wildman SA, Hoffmann FM, Keck JL. A High-Throughput Screening Strategy to Identify Inhibitors of SSB Protein-Protein Interactions in an Academic Screening Facility. SLAS Discov. 2018 Jan;23(1):94-101. doi: 10.1177/2472555217712001. Epub 2017 Jun 1. PubMed PMID: 28570838; PubMed Central PMCID: PMC5667550.

Zhang F, Braun DR, Ananiev GE, Hoffmann FM, Tsai IW, Rajski SR, Bugni TS. Biemamides A-E, Inhibitors of the TGF-β Pathway That Block the Epithelial to Mesenchymal Transition. Org Lett. 2018 Sep 21;20(18):5529-5532. doi: 10.1021/acs.orglett.8b01871. Epub 2018 Aug 30. PubMed PMID: 30160121; PubMed Central PMCID: PMC6207949.

2017

Ericksen SS, Wu H, Zhang H, Michael LA, Newton MA, Hoffmann FM, Wildman SA. Machine Learning Consensus Scoring Improves Performance Across Targets in Structure-Based Virtual Screening. J Chem Inf Model. 2017 Jul 24;57(7):1579-1590. doi: 10.1021/acs.jcim.7b00153.  PubMed PMID: 28654262; PubMed Central PMCID: PMC5872818.

Zhang F, Barns K, Hoffmann FM, Braun DR, Andes DR, Bugni TS. Thalassosamide, a Siderophore Discovered from the Marine-Derived Bacterium Thalassospira profundimaris. J Nat Prod. 2017 Sep 22;80(9):2551-2555. doi: 10.1021/acs.jnatprod.7b00328. Epub 2017 Aug 25. PubMed PMID: 28840714; PubMed Central PMCID: PMC5740872.

2016

Djamali A, Wilson NA, Sadowski EA, Zha W, Niles D, Hafez O, Dorn JR, Mehner TR, Grimm PC, Hoffmann FM, Zhong W, Fain SB, Reese SR. Nox2 and Cyclosporine-Induced Renal Hypoxia. Transplantation. 2016 Jun;100(6):1198-210. doi: 10.1097/TP.0000000000001137. PubMed PMID: 26950727; PubMed Central PMCID: PMC4874919.

2015

Zhao Z, Wang L, James T, Jung Y, Kim I, Tan R, Hoffmann FM, Xu W. Reciprocal Regulation of ERα and ERβ Stability and Activity by Diptoindonesin G. Chem Biol. 2015 Dec 17;22(12):1608-21. doi: 10.1016/j.chembiol.2015.10.011. Epub 2015 Dec 3. PubMed PMID: 26670079; PubMed Central PMCID: PMC4767166.

2014

Bansal, M., Yang, J., Karan, C., Menden, M. P., Costello, J. C., Tang, H., Xiao, G., Li, Y., Allen, J., Zhong, R., Chen, B., Kim, M., Wang, T., Heiser, L. M., Realubit, R., Mattioli, M., Alvarez, M. J., Shen, Y., NCI-DREAM Community (including Hoffmann, F. M.), Gallahan, D., Singer, D., Saez-Rodriguez, J., Xie, Y., Stolovitzky, G., and Califano, A.  A Community Computational Challenge to Predict the Activity of Pairs of Compounds.  Nat. Biotechnol., 32(12):  1213-1222, 2014.

Goel, S. A., Guo, L.-W., Wang, B., Guo, S., Roenneburg, D., Ananiev, G. E., Hoffmann, F. M., and Kent, K. C.  High-Throughput Screening Identifies Idarubicin as a Preferential Inhibitor of Smooth Muscle versus Endothelial Cell Proliferation.  PLoS One, 9(2):e89349, 2014.

2013

Goodman, C. A., McNally, R. M., Hoffmann, F. M., and Hornberger, T. A.  Smad3 Induces Atrogin-1, Inhibits mTOR and Protein Synthesis, and Promotes Muscle Atrophy in Vivo.  Mol. Endocrinol., 27(11): 1946-1957, 2013.

Ozawa, M., Shimojima, M., Goto, H., Watanabe, S., Hatta, Y., Kiso, M., Furuta, Y., Horimoto, T., Peters, N. R., Hoffmann, F. M., and Kawaoka, Y.  A Cell-Based Screening System for Influenza A Viral RNA Transcription/Replication Inhibitors.  Sci. Rep., 3:1106, 2013.

Zeng, H., Wu, J., Bedford, M. T., Sbardella, G., Hoffmann, F. M., Bi, K., and Xu, W.  A TR-FRET-Based Functional Assay for Screening Activators of CARM1.  ChemBioChem, 14(7): 827-835, 2013.

2012

Das, S., Becker, B. N., Hoffmann, F. M., and Mertz, J. E.  Reversal of Transforming Growth Factor-β Induced Epithelial-to-Mesenchymal Transition and the ZEB Proteins.  Fibrogenesis Tissue Repair, 5(Suppl 1): S28, 2012. 

Tomasini-Johansson, B. R., Johnson, I. A., Hoffmann, F. M., and Mosher, D. F.  Quantitative Microtiter Fibronectin Fibrillogenesis Assay:  Use in High Throughput Screening for Identification of Inhibitor Compounds.  Matrix Biol., 31: 360-367, 2012.

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