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Daniel Greenspan

Professor of Pathology and Laboratory Medicine and Pharmacology

Address:

5675 Medical Sciences

Telephone:

262-4676

Email:

dsgreens@wisc.edu

Research Fields:

Mouse Genetics

Human and Mammalian

Molecular Genetics

Research Interests

Genes important to vertebrate development and human disease

Research Description

Our focus is on genes and gene products important to vertebrate development and human disease. We discover developmentally important genes, map them in human and other genomes, study their structures and regulation of expression, and determine their involvement in normal morphogenesis and in genetic abnormalities. For, example, we’ve isolated and characterized the locus for the disfiguring and ultimately fatal heritable skin disorder dystrophic epidermolysis bullosa. We’ve also found and characterized the locus for Ehlers-Danlos syndrome type I (EDSI), which occurs in about 1 in 20,000 births and produces individuals with fragile connective tissues. A growing focus of the lab has evolved from our characterization of the mammalian homologue of a gene involved in pattern formation of Drosophila embryos. Moreover, study of knockout mice for this gene led us to isolate a related gene capable of partial complementation. This second gene is a heart segmentation gene necessary for the proper development of the valves and septa of the heart. We’ve discovered additional members of this gene family and are engaged in deciphering their roles in development and disease. We believe them to orchestrate the deposition of extracellular matrix and the activation of growth factors during morphogenetic processes. Molecular biology, genetics, biochemistry, cell biology, histology and transgenic techniques are employed.

Representative Publications

• Steiglitz, B.M., Kreider, J.M., Frankenburg, E.P., Pappano, W.N., Hoffman, G.G., Meganck, J.A., Liang, X., Hook. M., Birk, D.E., Goldstein, S.A. and Greenspan, D.S. 2006. Procollagen C proteinase enhancer 1 genes are important determinants of the mechanical properties and geometry of bone and the ultrastructure of connective tissues. Mol. Cell. Biol. 26:238-249.
• Ge, G., Hopkins, D. R., Ho, W.-B., and Greenspan, D. S. GDF11 forms a BMP1- activated latent complex that can modulate nerve growth factor-induced differentiation of PC12 cells. Mol. Cell. Biol. 25, 5846-5858 (2005).
• Scott, I.C., Blitz, I.L., Pappano, W.N., Maas, S.A., Cho, K.W.Y., and Greenspan, D.S.: Twisted gastrulation homologs are extracellular cofactors in antagonism of BMP signaling. Nature 410, 475-478 (2001).
• Clark, T.G., Conway, S.J., Scott, I.C., Labosky, P.A., Winnier, G., Bundy, J., Hogan, B.L.M., and Greenspan, D.S. 1999. The mammalian tolloid-like 1 gene, Tll1, is necessary for normal septation and positioning of the heart. Development 126:2631-264.
• Kessler, E., K. Takahara, L. Biniaminov, M. Brusel, and D.S. Greenspan. 1996. Bone morphogenetic protein-1: the type I procollagen C-proteinase. Science 271:360-362.