William C. Aird, MD

Beth Israel Deaconess Medical Center

Beth Israel Deaconess Medical Center
Phone: (617) 667-1031
Fax: (617) 667-2913


waird@bidmc.harvard.edu

William C. Aird, MD

Beth Israel Deaconess Medical Center

EDUCATIONAL TITLES

  • Professor, Medicine, Harvard Medical School
  • MD, Hematology-Oncology, Beth Israel Deaconess Medical Center

Research Abstract

My lab is focused on studying how endothelial cell phenotypes are differentially regulated from site of the vascular tree to another. We employ a series of in vitro assays (co-culture, 3D cultures, transient and stable transfections) and in vivo assays (transgenic mice, homologous recombination, transplantation, systemic growth factor delivery, tumor xenografts) to elucidate the molecular mechanisms of endothelial cell heterogeneity. One of the questions we are actively pursuing is how endothelial cell gene expression is differentially regulated in tumor angiogenesis. We have identified a novel marker of tumor endothelium, termed endothelial cell specific molecule-1 (SEM-1). In contrast to most markers of tumor blood vessels, ESM-1 is not expressed in the developing vasculature of embryos. We have also identified promoter fragments of endothelial cell-specific genes that contain information for tumor endothelial cell-specific expression in transgenic mouse models. We are currently delineating the responsible regulatory DNA elements with the ultimate goal of developing novel targeting strategies for delivering biologically active genes to tumor endothelium.

Publications

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  • Dharaneeswaran H, Abid MR, Yuan L, Dupuis D, Beeler DL, Spokes K, Janes L, Sciuto T, Kang PM, Jaminet SC, Dvorak A, Grant MA, Regan E, Aird WC. FoxO1-Mediated Activation of Akt Plays a Critical Role in Vascular Homeostasis. Circ Res 2014. PubMed
  • Okada Y, Funahashi N, Tanaka T, Nishiyama Y, Yuan L, Shirakura K, Turjman AS, Kano Y, Naruse H, Suzuki A, Sakai M, Zhixia J, Kitajima K, Ishimoto K, Hino N, Kondoh M, Mukai Y, Nakagawa S, García-Cardeña G, Aird WC, Doi T. Endothelial Cell-Specific Expression of Roundabout 4 Is Regulated by Differential DNA Methylation of the Proximal Promoter. Arterioscler Thromb Vasc Biol 2014. PubMed
  • Zhang G, Yang L, Kim GS, Ryan K, Lu S, O'Donnell RK, Spokes K, Shapiro N, Aird WC, Kluk MJ, Yano K, Sanchez T. Critical role of sphingosine-1-phosphate receptor 2 (S1PR2) in acute vascular inflammation. Blood 2013; 122:443-55. PubMed
  • Zaslavsky A, Chou ST, Schadler K, Lieberman A, Pimkin M, Kim YJ, Baek KH, Aird WC, Weiss MJ, Ryeom S. The calcineurin-NFAT pathway negatively regulates megakaryopoiesis. Blood 2013; 121:3205-15. PubMed
  • Yoshikawa M, Mukai Y, Okada Y, Tsumori Y, Tsunoda S, Tsutsumi Y, Aird WC, Yoshioka Y, Okada N, Doi T, Nakagawa S. Robo4 is an effective tumor endothelial marker for antibody-drug conjugates based on the rapid isolation of the anti-Robo4 cell-internalizing antibody. Blood 2013; 121:2804-13. PubMed
  • Shirodkar AV, St Bernard R, Gavryushova A, Kop A, Knight BJ, Yan MS, Man HS, Sud M, Hebbel RP, Oettgen P, Aird WC, Marsden PA. A mechanistic role for DNA methylation in endothelial cell (EC)-enriched gene expression: relationship with DNA replication timing. Blood 2013. PubMed
  • Adams WJ, Zhang Y, Cloutier J, Kuchimanchi P, Newton G, Sehrawat S, Aird WC, Mayadas TN, Luscinskas FW, García-Cardeña G. Functional vascular endothelium derived from human induced pluripotent stem cells. Stem Cell Reports 2013; 1:105-13. PubMed
  • Tozawa H, Kanki Y, Suehiro JI, Tsutsumi S, Kohro T, Wada Y, Aburatani H, Aird WC, Kodama T, Minami T. Genome-wide approaches reveal functional IL-4 inducible STAT6 binding to the vascular cell adhesion molecule-1 promoter. Mol Cell Biol 2011. PubMed
  • Liu J, Yuan L, Molema G, Regan E, Janes L, Beeler D, Spokes KC, Okada Y, Minami T, Oettgen P, Aird WC. Vascular bed-specific regulation of the von Willebrand factor promoter in the heart and skeletal muscle. Blood 2011; 117:342-51. PubMed
  • Wada Y, Li D, Merley A, Zukauskas A, Aird WC, Dvorak HF, Shih SC. A multi-gene transcriptional profiling approach to the discovery of cell signature markers. Cytotechnology 2010. PubMed
  • Damrauer SM, Fisher MD, Wada H, Siracuse JJ, da Silva CG, Moon K, Csizmadia E, Maccariello ER, Patel VI, Studer P, Essayagh S, Aird WC, Daniel S, Ferran C. A20 inhibits post-angioplasty restenosis by blocking macrophage trafficking and decreasing adventitial neovascularization. Atherosclerosis 2010; 211:404-8. PubMed
  • Nassiri M, Liu J, Kulak S, Uwiera RR, Aird WC, Ballermann BJ, Jahroudi N. Repressors NFI and NFY participate in organ-specific regulation of von Willebrand factor promoter activity in transgenic mice. Arterioscler Thromb Vasc Biol 2010; 30:1423-9. PubMed
  • Aird WC, Kwaan HC. Under-recognized significance of endothelial heterogeneity: hemostasis, thrombosis, and beyond. Semin Thromb Hemost 2010; 36:225-6. PubMed
  • Aird WC. Proximate and evolutionary causation of endothelial heterogeneity. Semin Thromb Hemost 2010; 36:276-85. PubMed
  • Suehiro JI, Hamakubo T, Kodama T, Aird WC, Minami T. Vascular endothelial growth factor activation of endothelial cells is mediated by early growth response-3. Blood 2010; 115:2520-32. PubMed
  • Jin E, Liu J, Suehiro J, Yuan L, Okada Y, Nikolova-Krstevski V, Yano K, Janes L, Beeler D, Spokes KC, Li D, Regan E, Shih SC, Oettgen P, Minami T, Aird WC. Differential roles for ETS, CREB, and EGR binding sites in mediating VEGF receptor 1 expression in vivo. Blood 2009; 114:5557-66. PubMed
  • Song H, Suehiro J, Kanki Y, Kawai Y, Inoue K, Daida H, Yano K, Ohhashi T, Oettgen P, Aird WC, Kodama T, Minami T. Critical role for GATA3 in mediating Tie2 expression and function in large vessel endothelial cells. J Biol Chem 2009; 284:29109-24. PubMed
  • Minami T, Yano K, Miura M, Kobayashi M, Suehiro J, Reid PC, Hamakubo T, Ryeom S, Aird WC, Kodama T. The Down syndrome critical region gene 1 short variant promoters direct vascular bed-specific gene expression during inflammation in mice. J Clin Invest 2009; 119:2257-70. PubMed
  • Baek KH,Zaslavsky A,Lynch RC,Britt C,Okada Y,Siarey RJ,Lensch MW,Park IH,Yoon SS,Minami T,Korenberg JR,Folkman J,Daley GQ,Aird WC,Galdzicki Z,Ryeom S. Down's syndrome suppression of tumour growth and the role of the calcineurin inhibitor DSCR1. Nature 2009; 459:1126-30. PubMed
  • Lee CW, Lin CC, Luo SF, Lee HC, Lee IT, Aird WC, Hwang TL, Yang CM. Tumor necrosis factor-alpha enhances neutrophil adhesiveness: induction of vascular cell adhesion molecule-1 via activation of Akt and CaM kinase II and modifications of histone acetyltransferase and histone deacetylase 4 in human tracheal smooth muscle c Mol Pharmacol 2008; 73:1454-64. PubMed
  • Aird WC. Endothelium in health and disease. Pharmacol Rep 2008; 60:139-43. PubMed
  • Abid MR, Spokes KC, Shih SC, Aird WC. NADPH oxidase activity selectively modulates vascular endothelial growth factor signaling pathways. J Biol Chem 2007; 282:35373-85. PubMed
  • Hwa C, Aird WC. The history of the capillary wall: doctors, discoveries, and debates. Am J Physiol Heart Circ Physiol 2007; 293:H2667-79. PubMed
  • Hawkins BJ, Solt LA, Chowdhury I, Kazi AS, Abid MR, Aird WC, May MJ, Foskett JK, Madesh M. G protein-coupled receptor Ca2+-linked mitochondrial reactive oxygen species are essential for endothelial/leukocyte adherence. Mol Cell Biol 2007; 27:7582-93. PubMed
  • Shapiro NI, Yano K, Okada H, Fischer C, Howell M, Spokes KC, Ngo L, Angus DC, Aird WC. A PROSPECTIVE, OBSERVATIONAL STUDY OF SOLUBLE FLT-1 AND VASCULAR ENDOTHELIAL GROWTH FACTOR IN SEPSIS. Shock 2007. PubMed
  • Feng J, Yano K, Monahan-Earley R, Morgan ES, Dvorak AM, Sellke FW, Aird WC. Vascular bed-specific endothelium-dependent vasomomotor relaxation in the hagfish, Myxine glutinosa. Am J Physiol Regul Integr Comp Physiol 2007; 293:R894-900. PubMed
  • Aird WC. Vascular bed-specific thrombosis. J Thromb Haemost 2007; 5 Suppl 1:283-91. PubMed
  • Okada Y, Yano K, Jin E, Funahashi N, Kitayama M, Doi T, Spokes K, Beeler DL, Shih SC, Okada H, Danilov TA, Maynard E, Minami T, Oettgen P, Aird WC. A three-kilobase fragment of the human Robo4 promoter directs cell type-specific expression in endothelium. Circ Res 2007; 100:1712-22. PubMed
  • Sternberg DW, Aird W, Neuberg D, Thompson L, MacNeill K, Amrein P, Shulman LN. Treatment of patients with recurrent and primary refractory acute myelogenous leukemia using mitoxantrone and intermediate-dose cytarabine: a pharmacologically based regimen. Cancer 2000; 88:2037-41. PubMed
  • Seguin C, Abid MR, Spokes KC, Schoots IG, Brkovic A, Sirois MG, Aird WC. Priming effect of homocysteine on inducible vascular cell adhesion molecule-1 expression in endothelial cells. Biomed Pharmacother 2008; 62:395-400. PubMed
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