Faculty: Department of Molecular Genetics: Ohio State University:

Michael Weinstein

216 Biosciences Building
484 W 12th Avenue
Columbus, OH 43210-1292
Phone: 614/688-0164
Email/web:
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Focus

Role of Transforming Growth Factor Beta (TGFß ) in mammalian embryogenesis, tumorigenesis, and disease.

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. Conditional Mutagenesis

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.

Publications

Debies M, Waters W, Taffany D, Spahich N, Festing M, Weinstein M. 2007. SARA, a FYVE Domain Containing Protein Linked To TGF-Ã Signaling, Is Not Required For Murine Viability and Fertility. Mol Cell Biol. under revision.
Liu Y, Lasse S, Bail S,Thompson JC, Kiledjian M, Weinstein M. 2007. Smif/Dcp1a, a constituent of mRNA decapping complexes also thought to function in TGFb signaling, is essential for mammalian placentogenesis. Dev Biol. Submitted.
Pavel E, Zhao W, Powell KA, Weinstein M, Kirschner LS. 2007. Analysis of a new allele of limb deformity (ld) reveals tissue- and age-specific transcriptional effects of the Ld Global Control Region. Int J Dev Biol. 51(4):273-81.
Acharyya S, Villalta SA, Bakkar N, Bupha-Intr T, Janssen PM, Carathers M, Li ZW, Beg AA, Ghosh S, Sahenk Z, Weinstein M, Gardner KL, Rafael-Fortney JA, Karin M, Tidball JG, Baldwin AS, Guttridge DC. 2007. Interplay of IKK/NF-kappaB signaling in macrophages and myofibers promotes muscle degeneration in Duchenne muscular dystrophy. J Clin Invest. Apr;117(4):889-901.
Dorrance AM, Liu S, Yuan W, Becknell B, Arnoczky KJ, Guimond M, Strout MP, Feng L, Nakamura T, Yu L, Rush LJ, Weinstein M, Leone G, Wu L, Ferketich A, Whitman SP, Marcucci G, Caligiuri MA. 2006. Mll partial tandem duplication induces aberrant Hox expression in vivo via specific epigenetic alterations. J Clin Invest. 116(10):2707-16.
Yu J, Wei M, Becknell B, Trotta R, Liu S, Boyd Z, Jaung MS, Blaser BW, Sun J, Benson DM Jr, Mao H, Yokohama A, Bhatt D, Shen L, Davuluri R, Weinstein M, Marcucci G, Caligiuri MA. 2006. Pro- and antiinflammatory cytokine signaling: reciprocal antagonism regulates interferon-gamma production by human natural killer cells. Immunity. 24(5):575-90.
Weinstein, M., and Deng, C. X. 2006. Genetic disruptions within the murine genome reveal the numerous roles of the Smad gene family in development, disease, and cancer. Smad signal Transduction: Smads in proliferation, differentiation and disease (Dordrecht, Springer). Editors: Ten Dijke, P. and Heldin, Carl-Henrik. Vol 5, Chapter 8, 151-176.