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Advances in our understanding of fundamental biological events can often be made by the analysis of defects manifested in inherited diseases. The genes responsible for these genetic syndromes often encode proteins that act at critical points of the pathways that control fundamental biological processes such as cell division, differentiation, and cell death. This approach has lead to the discovery of novel gene products and/or biochemical pathways involved in disease, genes that in turn play a fundamental role in normal biological processes.
My laboratory has taken this genetic approach for the study of angiogenesis, beginning with Mendelian disorders of vascular dysplasia and progressing to more complex vascular phenotypes. Our objectives are twofold: (1) to gain specific knowledge of the pathology observed in these disorders, and (2) to provide basic knowledge on the role of these genes and gene products in angiogenesis. The first step is to identify the genetic loci that underlie these syndromes. These mapping and positional cloning endeavors become the basis for future molecular biological studies on the role of the mutant gene products in the pathology of the disease, and the role of the normal proteins in vascular development. In order to investigate disease mechanism and pathogenesis, we then create an appropriate transgenic or knockout mouse as an animal model of the disease.
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Roberto J Alcazar-Felix,Abhinav Srinath,Stephanie Hage, Akash Bindal, Andrew Ressler, Peter Pytel, Sammy Allaw,Romuald Girard,Douglas A Marchuk,Issam A Awad,Sean P Polster
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Associationpp.107699-107699, (2024)
Cell Communication and Signalingno. 1 (2024): 1-16
GENETICSno. 4 (2023)
STROKEno. 11 (2023): 2906-2917
Carol J. Gallione,Matthew R. Detter, Adrienne Sheline, Henrietta M. Christmas,Cornelia Lee,Douglas A. Marchuk
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