Research interests

Our laboratory works to understand how endoglin, a TGFb receptor-associated transmembrane protein, and the TGFb receptors, regulate the process of angiogenesis and the occurrance of vascular pathology. In humans, mutations in the genes encoding either endoglin, or the TGFb receptor ALK1, cause the vascular disease hereditary hemorrhagic telangiectasia (HHT). Currently, we are interested in those aspects of endoglin's structure that regulate its phosphorylation by the TGFb receptors, and how endoglin phosphorylation effects cell physiology within a variety of tissue contexts. Understanding the details of endoglin's function will lead to mechanistic insights into the processes of cell adhesion, migration, and invasion, and will advance our understanding of a variety of complex biological processes, including vascular development, vascular disease, and cancer progression.

Publications

• Romero D, Terzic A, Conley BA, Craft C, Jovanovic B, Bergan R, and Vary CPH. Endoglin phosphorylation by ALK2 contributes to the regulation of prostate cancer cell migration. Carcinogenesis 2009. [Epub ahead of print]

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• Mancini ML, Terzic A, Conley BA, Oxburgh LH, Nicola T, and Vary CPH. Endoglin Plays Distinct Roles in Vascular Smooth Muscle Cell Recruitment and Regulation of Arteriovenous Identity During Angiogenesis. Dev Dyn 2009; 238:2479-2493.

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• Mouta-Bellum C, Kirov A, Miceli-Libby L, Mancini ML, Petrova TV, Liaw L, Prudovsky I, Thorpe PE, Miura N, Cantley LC, Alitalo K, Fruman DA, and Vary CPH. Organ-specific lymphangiectasia, arrested lymphatic sprouting, and maturation defects resulting from gene-targeting of the PI3K regulatory isoforms p85alpha, p55alpha, and p50alpha. Dev Dyn 2009; 238:2670-2679.

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• Nikopoulos GN, Martins JF, Adams TL, Karaczyn A, Adams D, Vary C, Verdi JM. NRAGE: A Potential Rheostat During Branching Morphogenesis. Mech Dev 2009; 126:337-349.

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• Romero, D, Iglesias, M, Vary, CPH, and Quintanilla, M. Functional blockade of Smad4 leads to a decrease in β-catenin levels and signaling activity in human pancreatic carcinoma cells. Carcinogenesis 2008; 5:1070-1076.

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• Craft, CS, Li, Xu, Romero, D, Vary, CPH, and Bergan, RC. Genistein induces phenotypic reversion of endoglin deficiency in human prostate cancer cells. Mol Pharmacol 2008; 73:235-242.

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• Bernabeu C, Conley BA, and Vary CPH. Novel Biochemical Pathways of Endoglin in Vascular Cell Physiology. J Cell Biochem 2007; 102:1375-1388.

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• Mancini ML, Verdi JM, Conley BA, Nicola T, Spicer DB, Oxburgh LH, and Vary CPH. Endoglin is required for myogenic differentiation potential of neural crest stem cells. Dev Biol, 2007; 308: 520-533.

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• Craft CS, Romero D, Vary CPH, and Bergan RC. Endoglin inhibits prostate cancer motility via activation of the ALK2-Smad1 pathway. Oncogene, 2007; 26:7240-7250.

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• Santibanez JF, Letamendia A, Perez-Barriocanal F, Silvestri C, Saura M, Vary CPH, Lopez-Novoa JM, Attisano L, Bernabeu C. Endoglin increases eNOS expression by modulating Smad2 protein levels and Smad2-dependent TGF-b signaling. J Cell Phys 2007; 210:456-468.

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• Koleva RI, Conley, A, Romero D, Riley KS, Marto JA, Lux A, Vary, CPH. Endoglin structure and function: Determinants of endoglin phosphorylation by TGFb receptors. J Biol Chem 2006; 281:25110-25123.

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Community/University Service

Dr. Vary is a long-standing member of the Maine Medical Center (MMC) Mentored Research Committee, is a member of the new MMC Clinical Research Oversite Committee, Chairs the MMC Institutional Biosafety Committee, and serves as an alternate on this institutions IRB. He has hosted MMC residents, MD fellows, Post-doctoral fellows and graduate students in his laboratory. He currently holds the positions of adjunct associate professor at the University of Southern Maine and in the University of Vermont College of Medicine. He is also an associate of the Graduate Faculty in the University of Maine Graduate School of Biomedical Sciences in the Institute for Molecular Biophysics and the Functional Genomics Program. In addition, Dr. Vary serves as chair of the Maine Technology Institute Biotechnology Sector Board, and is a member of the HHT Foundation International Global Research and Medical Advisory Board.