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F. Michael Hoffmann, Ph.D.

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F.M. Hoffmann photo Romnes Professor of Oncology and Medical Genetics

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

Office: 7553 Wisconsin Institutes for Medical Research
Office - (608) 263-2890; Lab - (608) 262-8854
Email: hoffmann@oncology.wisc.edu

Small Molecule Screening & Synthesis Facility

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Research Interests: How does the Smad-dependent TGF-β signaling pathway mediate such different cellular responses in different cell types and specifically in pancreatic cancer, diabetic nephropathy and muscular dystrophy.

Research Description: The TGF-β signal transduction pathway plays key roles in normal functions such as wound healing and suppression of the immune system.  But TGF-β signaling has also been implicated as a factor in cancer, as a causative agent in all fibrotic diseases including diabetic nephropathy, and as an exacerbating factor in muscle weakness in muscular dystrophy.  In human tumors, such as pancreatic tumors, the normal growth inhibitory function of TGF-β is lost.  In some advanced tumors, the pathway is altered such that TGF-β stimulates proliferation of the cancer cell.  TGF-β also promotes tumor growth and spread by enhancing cell migration, angiogenesis, immune suppression, and stromal activation.

The Smad proteins and several Smad-interacting transcription factors provide an array of new targets that could be potential sites for therapeutic intervention. There are currently no therapeutic agents that act on these targets in the TGF-β pathway.

Our working hypothesis is that inhibition of specific Smad protein-protein interactions will selectively attenuate certain cellular responses to TGF-β, e.g., inhibit fibrosis but maintain cell proliferation control and immunosuppression by TGF-β.

We are using a genetic approach to define protein binding hotspots on the surfaces of Smad proteins and characterizing the effects of these missense mutations on Smad functions in Smad-deficient cells. 

My interests in academic drug discovery and roles as the faculty advisor to the campus high throughput screening facility and co-leader of the Experimental Therapeutics Program in the Carbone Cancer Center have led to numerous collaborative projects with other UW-Madison faculty.

Selected recent publications

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.

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.

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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