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overview Alexander Awgulewitsch is Associate Professor of Medicine and Director of the MUSC Transgenic Mouse Core Facility. He received a Ph.D. (Dr. rer. nat.) degree at the Institute of Genetics, University of Düsseldorf, Germany, in 1984. He did postdoctoral studies in mammalian developmental genetics with the late Dr. Frank Ruddle at Yale University until 1988. That same year he was appointed Assistant Professor at the Department of Biochemistry at MUSC. He was promoted to Associate Professor in 1992 before joining the faculty of the Department of Medicine in 1993. A primary interest of Dr. Awgulewitsch is in studying the roles of Hox transcriptional regulators in development and disease. These genes are critical for specifying positional identities during embryonic patterning. This involves phylogenetically conserved transcriptional control mechanisms for directing spatially restricted Hox expression patterns as illustrated by the functional conservation of Hox transcriptional enhancers from the fruit fly in transgenic mice (Awgulewitsch & Jacobs 1992; Papenbrock et al. 1998). Apparently, these positional identities are retained to some degree in the adult organism where Hox genes are believed to control tissue homeostasis by regulating local cell differentiation events. To this end, a current focus of the lab is on determining the role of certain Hox genes in the adult cardiovascular system where they exhibit topographic expression patterns in vascular smooth muscle and endothelial cells (Pruitt et al. 2008). Our experimental approach for validating this paradigm of a vascular topographic Hox code includes disrupting this code in mice. Using a novel integrated Tet-regulatory transgenic system, vascular expression patterns of topographically restricted Hox genes are re-directed in an inducible manner (Pruett et al. 2012). The resulting region-specific structural and molecular changes in the vessel wall provide important insight into Hox-dependent genetic pathways underlying various vascular disorders that exhibit topographic patterns (e.g. atherosclerosis and aortic aneurysms) (Awgulewitsch & Majesky 2013). Furthermore, this work yields insight into Hox-regulated angiogenic pathways during wound healing and tumor growth. A second system for gaining insight into Hox-regulated pathways is hair follicle biology with Hoxc13 being used as a paradigm. Hoxc13 is essential for proper differentiation of keratinocytes of different lineages. Using Hoxc13 transgenic mice, we have identified numerous Hoxc13-regulated target genes of diverse functional categories, including keratins, desmosomal cadherins, and transcription factors (e.g. Tkatchenko et al. 2001 Pruett et al. 2004; Potter et al. 2006, 2011). This ongoing work involves a long-standing collaboration with Dr. Sundberg from The Jackson Laboratory in Maine.
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