Calvin Vary


  • PhD Biological Chemistry, Michigan State University


Dr. Vary is a senior scientist at the Maine Medical Center Research Institute. His training is in biochemistry, cell and molecular biology.  Dr. Vary directs the MMCRI Nucleic Acid, Protein and Cell Imaging core, and uses mass spectrometry and confocal microscopy to investigate protein expression and trafficking in endothelial cells. His current areas of interest include angiogenesis, vascular development, disease, and tumor-microenvironment interactions in prostate cancer. He is a Professor of Medicine and a Member of the Cell, Molecular, and Developmental Biology Program, Tufts Sackler School of Graduate Biomedical Sciences Tufts University School of Medicine, a member of the Functional Genomics Faculty and chairs the GSBS Cell and Molecular Biology Curriculum Committee.

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.

Selected Service

Dr. Vary is a member of the Maine Medical Center (MMC) Scientific Research Committee. He chairs the MMC Institutional Biosafety Committee, and serves as an alternate on this institutions IRB. He has mentored 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 Professor of Medicine at the Tufts University School of Medicine, and is associated with the Tufts Sackler School of Graduate Biomedical Sciences. 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 InstituteBiotechnology Sector Board, and is a member of the HHT Foundation International Global Research and Medical Advisory Board.

Selected Grants

  • 2014 to 2017 — Endoglin is a novel Notch target gene – implications for vascular signaling from American Heart Association

Selected Publications

  • Young K, Krebs LT, Tweedie E, Conley B, Mancini M, Arthur HM, Liaw L, Gridley T, Vary C. Endoglin is required in Pax3-Derived Cells for Embryonic Blood Vessel Formation. Dev Biol. 2016;409:95-105. Read Abstract
  • Young K, Tweedie E, Conley B, Ames JJ, FitzSimons M, Brooks P, Liaw L, Vary CPH. BMP9 crosstalk with the Hippo pathway regulates endothelial cell matricellular and chemokine responses. PLoS ONE. 2015; Apr 24;10(4):e0122892 Read Abstract
  • Stohn JP, Wang Q, Siviski ME, Kennedy K, Jin Y, Kacer D, DeMambro V, Liaw L, Vary CP, Rosen CJ, Prudovsky O, Lindner V. Cthrc1 Controls Adipose Tissue Formation, Body Composition, and Physical Activity. Obesity (Silver Spring). 2015 Aug;23(8):1633-42.Read Abstract
  • Rostama B, Turner JE, Seavey GT, Norton CR, Gridley T, Vary CP, Liaw L. DLL4/Notch1 and BMP9 Interdependent Signaling Induces Human Endothelial Cell Quiescence via P27KIP1 and Thrombospondin-1. Arterioscler Thromb Vasc Biol. 2015. Read Abstract
  • Ames JJ, Contois L, Caron JM, Tweedie E, Yang X, Friesel R, Vary C1, Brooks PC. Identification of an Endogenously Generated Cryptic Collagen Epitope (XL313) That May Selectively Regulate Angiogenesis by an Integrin Yes-associated Protein (YAP) Mechano-transduction Pathway. J Biol Chem. 2016;291:2731-50. Read Abstract
  • Contois L, Akalu A, Caron JM, Tweedie E, Cretu A, Henderson T, Liaw L, Friesel R, Vary C, Brooks PC. Inhibition of tumor-associated avb3 integrin regulates the angiogenic switch by enhancing expression of IGFBP-4 leading to reduced melanoma growth and angiogenesis in vivo. Angiogenesis.
  • Kirov A, Kacer D, Conley BA, Vary CP, Prudovsky I. AHNAK2 Participates in the Stress-Induced Nonclassical FGF1 Secretion Pathway. J Cell Biochem. J Cell Biochem. 2015 Aug;116(8):1522-31 Read Abstract
  • Uygur B, Abramo K, Leikina E, Vary C, Liaw L, and Wu W. SLUG is a direct transcriptional repressor of PTEN tumor suppressor. Prostate. 2015 Jun 15;75(9):907-16. Read Abstract
  • Yang X, Liaw L, Prudovsky I, Brooks, PC, Vary, C, Oxburgh, L, and Friesel R. FGF Signaling in the Vasculature. Current Atherosclerosis Reports. 2015 Jun;17(6):509.
  • Duarte CW, Murray K, Lucas FL, Fairfield K, Miller H, Brooks PC, Vary CP. Improved Survival Outcomes in Cancer Patients with Hereditary Hemorrhagic Telangiectasia. Read Abstract
  • Favreau AJ, Vary CP, Brooks PC, Sathyanarayana P. Cancer Med. 2014 Apr;3(2):265-72. Cryptic collagen IV promotes cell migration and adhesion in myeloid leukemia. Read Abstract
  • Rostama B, Peterson SM, Vary CPH, and Liaw L. Notch signal integration in the vasculature during remodeling. Vascular Pharmacology Read Abstract
  • Gong Y, Qing H, Yang X, Gower L, Prudovsky I, Vary CPH, Brooks P, and Friesel RE. Sprouty4 regulates endothelial cell migration via modulating Integrin ?3 stability through c-Src. Angiogenesis. 2013 Oct;16(4):861-75.
  • Breen MJ, Moran DM, Liu W, Huang X, Vary CPH, and Bergan RC. Endoglin-Mediated Suppression of Prostate Cancer Invasion Is Regulated by Activin and Bone Morphogenetic Protein Type II Receptors. 2013. PLoS One. 2013 Aug 13;8(8):e72407.
  • Contois L, Nugent DP, Caron JM, Cretu A, Tweedie E, Akalu A, et al. Insulin-Like Growth Factor Binding Protein-4 (IGFBP-4) Differentially Inhibits Growth Factor-Induced Angiogenesis. J Biol Chem. 2012;287(3):1779-89. Read Abstract
  • Prudovsky I, Vary CP, Markaki Y, Olins AL, Olins DE. Phosphatidylserine colocalizes with epichromatin in interphase nuclei and mitotic chromosomes. Nucleus. 2012;3:200-210.Read Abstract
  • Young K., Conley B.A., Romero D, Tweedie E, O’Neill CF, Pinz I, Brogan L, Lindner V, Liaw L, and Vary CPH. 2012. BMP9 Regulates Endoglin-dependent Chemokine Responses in Endothelial Cells. Blood. 2012;120:4263-4273. Read Abstract
  • Venkatesh D, Fredette N, Rostama B, Tang Y, Vary CPH, Liaw L and Urs S. RhoA mediated signaling in Notch-induced senescence like growth arrest and endothelial barrier dysfunction. Arterioscler Thromb Vasc Biol. 2011;31(4):876-882. Read Abstract
  • Romero D, O’Neill C, Terzic A, Contois L, Young K, Conley BA, Bergan RC, Brooks PC, Vary CPH. Endoglin regulates cancer-stromal cell interactions in prostate tumors. Cancer Research: 2011; 71(10); 3482–3493. Read Abstract or Download file (PDF)
  • Tang Y, Yang X, Friesel RE, Vary CPH, and Liaw L. Mechanisms of TGF? Induced Differentiation in Human Vascular Smooth Muscle Cells. J. Vascular Research. 2011; 48:485–494. Read Abstract
  • Mathers A, Smith RP, Cahill B, Lubelczyk C, Elias SP, Lacombe E, Morris SR, Vary CP, Parent CE, Rand PW. Strain diversity of Borrelia burgdorferi in ticks dispersed in North America by migratory birds. J Vector Ecol. 2011;36(1):24-9. Read Abstract
  • 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. 2010;31(3):359-66. PMCID: 2832542. Read Abstract or Download file (PDF)
  • Tang Y, Urs S, Boucher J, Bernaiche T, Venkatesh D, Spicer DB, Vary CP, Liaw L. Notch and TGF-b signaling pathways cooperatively regulate vascular smooth muscle cell differentiation. J Biol Chem. 2010;285(23):17556-63. PMCID: 2878520. Read Abstract
  • Garrido-Martin EM, Blanco FJ, Fernandez-L A, Vary CP, Lee U, Friedman SL, Botella LM, Bernabeu C. Characterization of the human Activin-A receptor type II-like kinase 1 (ACVRL1) promoter and its regulation
    by Sp1. BMC Mol Biol. 2010;11(1):51. PMCID: 2906440. Read Abstract
  • Liu J., Shao L, Romero D, Vary CP, Wu W. Slug Inhibits Proliferation of Human Prostate Cancer Cells via Downregulation of Cyclin D1 Expression. Prostate. 2010;70(16):1768-77. PMCID: 2943978. Read Abstract
  • Santibanez JF, Pérez-Gómez E, Fernandez-L A, Garrido-Martin EM, Carnero A, Malumbres M, Vary CPH, Quintanilla M, and Bernabéu C. The TGF-? co-receptor endoglin modulates the expression and transforming potential of H-Ras. Carcinogenesis. 2010;31(12):2145-2154. PMC Journal – In Process. Read Abstract
  • Lakshman M, Huang X, Ananthanarayanan V, Jovanovic B, Liu Y, Craft CS, Romero D, Vary CPH, and Bergan RC. Endoglin suppresses human prostate cancer metastasis. Clin Exp Metastasis. 2011;28(1):39-53. PMC Journal – In Process.
  • Karaczyn A, Bani-Yaghoub M, Tremblay R, Kubu C, Cowling R, Adams TL, Prudosky I, Spicer D, Friesel R, Vary C, and Verdi JM. Two novel human NUMB isoforms provide a potential link between development and cancer. Neural Development. 2010; 5:31-46; PMCID: PMC3009962. Read Abstract
  • 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. Read Abstract or Download file (PDF)
  • 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. Read Abstract or Download file (PDF)
  • 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. PMC Journal – In Process. Read Abstract or Download file (PDF)
  • 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.
    Romero, D, Iglesias, M, Vary, CPH, and Quintanilla, M. Functional blockade of Smad4 leads to a decrease in ?-catenin levels and signaling activity in human pancreatic carcinoma cells. Carcinogenesis 2008; 5:1070-1076. Read Abstract or Download file (PDF)
  • Romero, D, Iglesias, M, Vary, CPH, and Quintanilla, M. Functional blockade of Smad4 leads to a decrease in beta-catenin levels and signaling activity in human pancreatic carcinoma cells. Carcinogenesis 2008; 5:1070-1076 Read Abstract or Download file (PDF)
  • 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. PMC2041841 Read Abstract or Download file (PDF)
  • Bernabeu C, Conley BA, and Vary CPH. Novel Biochemical Pathways of Endoglin in Vascular Cell Physiology. J Cell Biochem 2007; 102:1375-1388. PMC2199238 Read Abstract or Download file (PDF)
  • 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. PMC2199239 Read Abstract or Download file (PDF)
  • 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. Read Abstract or Download file (PDF)
  • Koleva RI, Austin CA, Kowaleski JM, Neems DS, Wang L, Vary CPH, Schlax, PJ. Interactions of ribosomal Protein S1 with DsrA and rpoS mRNA. Bioch Biophys Res Comm 2006; 348:662-668. Read Abstract or Download file (PDF)