F. Michael Hoffmann
Professor of Oncology and Medical Genetics
Ph.D., Cornell University, 1979
Postdoctoral Research: Harvard University
Address: 320 McArdle
Telephone: 263-2890
E-mail: fmhoffma@wisc.edu
Research Interests:
Using Chemical genetics to elucidate the roles of TGF in disease
Research Fields:
Cancer Genetics
Molecular Genetics
Research Description: TGF has been implicated in a broad variety of human diseases including cancer, immunoregulation, wound healing and tissue repair. In cancer, TGF facilitates the progression and spread of tumor cells. The tumor-derived TGF can aid tumorigenicity by direct actions on the cancer cell, by induction of angiogenesis, by local or systematic immunosuppression, and by alterations of stromal tissue, that facilitate invasiveness. A chemical genetics approach is being pursued to discover and charcterize in cell-based and animal models new small molecules that intervene in TGF signaling. The working hypothesis is that selective pertubation of TGF-responses may be achieved by understanding the specific interactions of phosphorylated Smad (Smad-P) complexes with other proteins and that selective intervention strategies are possible by interfering with a specific sub-set of Smad-P’s interactions. Chemical genetic methods are being used to perturb a distinct subset of Smad-P functions for evaluation in biological assays includinbg several cell-based and animal models of disease. The approach allows facile testing of combinatorial intervention strategies. The research will provide strategies and reagents for perturbing the TGF signaling pathway, identify structures of small molecules that are good ligands for Smad-P or other targets in the TGF pathway.
Representative Publications:
Zhao, B.M. and Hoffmann, F.M. 2006. Inhibition of Transforming Growth Factor-beta1-induced Signaling and Epithelial to Mesenchymal Transition by the Smad-binding Peptide Aptamer Trx-SARA. Mol. Biol. Cell. Jun 14.
Langenhan, J.M., Peters, N.R., Guzei, I.A., Hoffmann, F.M. and Thorson, J.S. 2005. Enhancing the anticancer properties of cardiac glycosides by neoglycorandomization. Proc. Natl. Acad. Sci. USA. 102:12305-10.
Martin, M., Ahern-Djamali, S.M., Hoffmann, F.M. and Saxton, W.M. 2005. Abl tyrosine kinase and its substrate Ena/VASP have functional interactions with kinesin-1. Mol. Biol. Cell. 16:4225-30.
Cui, Q., Lim, S.K., Zhao, B. and Hoffmann, F.M. 2005. Selective inhibition of TGF-beta responsive genes by Smad-interacting peptide aptamers from FoxH1, Lef1 and CBP. Oncogene. 24:3864-74.
Professor of Oncology and Medical Genetics
Ph.D., Cornell University, 1979
Postdoctoral Research: Harvard University
Address: 320 McArdle
Telephone: 263-2890
E-mail: fmhoffma@wisc.edu
Research Interests:
Using Chemical genetics to elucidate the roles of TGF in disease
Research Fields:
Cancer Genetics
Molecular Genetics
TGF has been implicated in a broad variety of human diseases including cancer, immunoregulation, wound healing and tissue repair. In cancer, TGF facilitates the progression and spread of tumor cells. The tumor-derived TGF can aid tumorigenicity by direct actions on the cancer cell, by induction of angiogenesis, by local or systematic immunosuppression, and by alterations of stromal tissue, that facilitate invasiveness. A chemical genetics approach is being pursued to discover and charcterize in cell-based and animal models new small molecules that intervene in TGF signaling. The working hypothesis is that selective pertubation of TGF-responses may be achieved by understanding the specific interactions of phosphorylated Smad (Smad-P) complexes with other proteins and that selective intervention strategies are possible by interfering with a specific sub-set of Smad-P’s interactions. Chemical genetic methods are being used to perturb a distinct subset of Smad-P functions for evaluation in biological assays includinbg several cell-based and animal models of disease. The approach allows facile testing of combinatorial intervention strategies. The research will provide strategies and reagents for perturbing the TGF signaling pathway, identify structures of small molecules that are good ligands for Smad-P or other targets in the TGF pathway.
Zhao, B.M. and Hoffmann, F.M. 2006. Inhibition of Transforming Growth Factor-beta1-induced Signaling and Epithelial to Mesenchymal Transition by the Smad-binding Peptide Aptamer Trx-SARA. Mol. Biol. Cell. Jun 14.
