Michael B. Weinstein, PhD
Assistant Professor
Department of Molecular Virology, Immunology & Medical Genetics
484 Tzagournis Medical Research Facility
420 W 12th Ave
Columbus , OH 43210
Phone: (614) 688-0164
Fax: (614) 292-4466
Weinstein.41@osu.edu

Research Interests
Smad proteins are the intracellular mediators of the transforming growth factor beta (TGF-b) superfamily. My laboratory will be focusing on role of Smad genes in the control of mammalian development, disease, and cancer using primarily knockout and transgenic mice. Our research has shown that Smad2 and Smad 4 are required for gastrulation, while Smad5 is involved in angiogenesis and crainiofacial development. Smad3 appears to mediate mucosal immunity. Ongoing studies are underway to pinpoint functions of other Smad genes in mammalian development and cancer.

I will be employing two broad approaches to the study of Smad genes. First, I will examine genetic interactions between the Smad's. I have discovered extensive interactions between the mediators Smad2 and Smad3, while others have found similar results between a ligand (the murine Nodal gene) and Smad2. My lab will continue analyzing the Smad2/3 mice, as well as broadening this analysis to multiple lines of Smad mutant mice and animals deficient for TGFb ligands.

The second approach will be to use conditional mutagenesis to examine further functions of Smad2. Because of its broad expression pattern and early lethality, Smad2 is an excellent candidate for this approach, which involves introducing recombinase recognition sites (loxP) into the murine genome. The recombinase (Cre) can be introduced genetically in a controlled fashion, resulting in a knockout limited to the domain of recombinase expression. Elimination of Smad2 in a temporal and tissue specific fashion will generate multiple insights into the functions of this gene, and will hopefully reveal information on the role of TGF-b signals in tumor formation.

Another arm of my research will involve the analysis of the Fibroblast Growth Factor Receptors (Fgfr's) in lung development. We already know that Fgfr1 and Fgfr2 are intimately involved in branching morphogenesis, and that Fgfr3 and Fgfr4 coordinately control a late step which is important in human diseases, particularly bronchopulmonary dysplasia. I am interested in using Fgfr3/4 mice to study late steps in lung development through a microarray approach.

Education & Training
Ohio State University, Columbus, OH 1984 B.S. Zoology

1985-1992 Graduate Studies, Biology Department, University of California, San Diego

University of California, San Diego, CA 1992 Ph.D.

1984-1985 Research Assistant, Ohio State University, Columbus, OH

1992-1995 Postdoctoral Fellow, Children's Hospital Medical Center, Cincinnati, Ohio

1995-1999 Postdoctoral Fellow,Genetics of Development and Disease Branch, National Institutes of Health, Bethesda, Maryland

Select Publications
Weinstein, M., Monga, P.S., Tang, Y., Mishra, L., and C-X. Deng. 2000. Smad proteins and HGF control parallel regulatory pathways that converge on the 1-integrin to promote normal liver development. Submitted.

Weinstein, M., Yang, X., and C-X. Deng. 1999. Functions of mammalian Smad genes as revealed by targeted mutagenesis. Cytokine Growth Factor Rev 2000 Mar-Jun;11(1-2):49-58

Xu, X., Brodie, S., Yang, X., Im, Y-M., Parks, W. T., Chen, L., Zhou, Y-X., Weinstein, M., Kim, S. J., and C. X. Deng. 1999. Haploid loss of the tumor suppressor Smad4/Dpc4 initiates gastric polyposis and cancer in mice. Oncogene 2000 Apr 6;19(15):1868-74

Ashcroft, G. S., Yang, X., Glick, A., Weinstein, M., Letterio, J., Mizel, D. E., Anzano, M., Greenwell-Wild, T., Wahl, S. M., Deng, C., and A. B. Roberts. 1999. Mice lacking SMAD 3 show accelerated wound healing and an impaired local inflammatory response. Nature Cell Biol. 1: 260-266

Yang, X., Castilla, L., Xu, X., Li, C., Gotay, J., Weinstein, M., Liu, P. P., and C. Deng. 1999. Angiogenesis defects and mesenchymal apoptosis in mice lacking SMAD5. Development 126: 1571-1580

Xu, X., Weinstein, M, Li, C., and C. Deng. 1998. Fibroblast growth factor receptors (FGFRs) and their roles in limb development. Cell and Tissue Res 296: 33-43

Shen, S, Weaver, Z., Xu, X., Li, C., Weinstein, M., Chen, L., Guan, X., Reid, T., and C. Deng. 1998. A mutation of murine Brca1 gene (Brca111) causes g-radiation hypersensitivity and genetic instability. Oncogene 17: 3115-3124

Weinstein, M., Yang, X., Li, C., Xu, X., Gotay, J., and C. Deng. 1998. Failure of extraembryonic membrane formation and mesoderm induction in embryos lacking the tumor suppressor smad2. PNAS 95:9378-9383

Weinstein, M., Xu, X., Ohyama, K., and C. Deng. 1998. Fibroblast Growth Factor Receptor-3 and Receptor-4 Function Cooperatively to Direct Alveogenesis in the Murine Lung. Development 125: 3615-3623