Mark L. Kahn, M.D., B.A.

faculty photo
Professor of Medicine
Department: Medicine
Graduate Group Affiliations

Contact information
11-123 Smilow Center for Translational Research
3400 Civic Center Boulevard, Bldg. 421
Philadelphia, PA 19104-5159
Office: (215) 898-9007
Fax: (215) 573-2094
Education:
B.A. (Science)
Brown University, 1984.
M.D. (Internal Medicine)
Brown University School of Medicine, 1987.
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Description of Research Expertise

Research Interests
Signaling pathways in angiogenesis and hemostasis.

Key words: Angiogenesis, vascular development, platelet, signaling.

Description of Research
My laboratory investigates signaling pathways in cardiovascular development and function. We have two general areas of interest: angiogenesis and platelet signaling. In some cases these areas intersect, e.g. the role of Syk and SLP-76 signaling downstream of platelet receptors that regulate lymphatic vascular development. Major projects in the lab include the following: Regulation of lymphatic vascular development by Syk and SLP-76 signaling. Mice lacking Syk or SLP-76 exhibit lethal vascular phenotypes that we have recently found to be due to a failure to separate emerging lymphatic vessels from pre-existing blood vessels. We have recently identified platelet interaction with lymphatic endothelial cells as the basis for this mechanism of vascular regulation. The long term goals of this project are to understand how platelets control endothelial function and lymphatic vascular development. Platelet immunoreceptor signaling. There are two platelet-specific immune-type receptors, GPVI and CLEC2, that activate Syk and SLP-76 signals. GPVI is a collagen receptor that functions in hemostasis and thrombosis. CLEC2 is a receptor for the lymphatic endothelial protein PDPN and regulates blood-lymphatic vascular interactions. We are presently using mouse genetic models to understand how these two receptors signal and to define their biological roles in vivo. Role of cerebral cavernous malformation (CCM) signaling pathway in vascular development and disease. CCMs are a common human vascular disease caused by loss of function mutations in 3 CCM proteins. We have recently shown that the Heart of Glass (HEG) receptor and CCM proteins are required in mouse and fish cardiovascular development. We are actively investigating how this recently identified pathway regulates endothelial function in development and causes CCMs.

Rotation Projects
1. Regulation of lymphatic vascular development by platelet signaling. 2. HEG-CCM signaling in fish and mouse models. 3. Novel receptor signaling pathways in mammalian cardiovascular development. 4. Development and application of lymphatic endothelial-specific gene knockouts.

Lab personnel:
Xiangjain Zheng, PhD-postdoctoral fellow; Zhiyng Zou, PhD-postdoctoral fellow; Cara Bertozzi, PhD student; Chiu-Yu Chen, MD-PhD student; Alec Schmaier, PhD student; Chong Xu, PhD-postdoctoral fellow; Jiping Xiao, PhD-postdoctoral fellow; Patricia Mericko, Lab Manager; Mei Chen Research, Specialist.

Selected Publications

Herzog BH, Fu J, Wilson SJ, Hess PR, Sen A, McDaniel JM, Pan Y, Sheng M, Yago T, Silasi-Mansat R, McGee S, May F, Nieswandt B, Morris AJ, Lupu F, Coughlin SR, McEver RP, Chen H, Kahn ML, Xia L: Podoplanin maintains high endothelial venule integrity by interacting with platelet CLEC-2. Nature Sept 2013 Notes: Epub ahead of print.

Rawnsley DR, Xiao J, Lee J, Liu X, Mericko-Ishizuka P, Kumar V, He J, Basu A, Lu M, Lynn FC, Pack M, Gasa R, Kahn ML: The transcription factor Atonal homolog 8 regulates Gata4 and Friend of Gata-2 during vertebrate development. Journal of Biology and Chemistry Jul 2013 Notes: Epub ahead of print.

Stanger BZ, Kahn ML: Platelets and tumor cells: a new form of border control. Cancer Cell 8(24): 9-11, Jul 2013.

Kahn ML, Rader DJ: Lymphatics as a new player in cholesterol transport. Cell Metabolism 17(5): 627-8, May 2013.

Zou Z, Enis D, Bui H, Khandros E, Kumar V, Jakus Z, Thom C, Yang Y, Dhillon V, Chen M, Lu M, Weiss MJ, Kahn ML: The secreted lymphangiogenic factor CCBE1 is essential for fetal liver erythopoiesis. Blood Apr 2013 Notes: Epub ahead of print.

Zou Z, Enis D, Bui H, Khandros E, Kumar V, Jakus Z, Thom C, Yang Y, Dhillon V, Chen M, Lu M, Weiss MJ, Kahn ML: The secreted lymphangiogenic factor CCBE1 is essential for fetal liver erythropoiesis. Blood Feb 2013.

Boulaftali Y, Hess PR, Getz TM, Cholka A, Stolla M, Mackman N, Owens AP 3rd, Ware,J Kahn ML, Bergmeier W.: Platelet ITAM signaling is critical for vascular integrity in inflammation. Journal of Clinical Investigation Jan 2013 Notes: [Epub ahead of print]

Hess PR, Rawnsley DR, Jakus Z, Yang Y, Sweet DT, Fu J, Herzog B, Lu MM, Nieswandt B, Oliver G, Makinen T, Xia L, Kahn ML: Platelets mediate lympho-venous hemostasis to maintain blood-lymphatic separation throughout life. Journal of Clinical Investigation 2013 Notes: in press.

Acton SE, Astarita JL, Malhotra D, Lukacs-Kornek V, Franz B, Hess PR, Jakus Z, Kuligowski M, Fletcher AL, Elpek KG, Bellemare-Pelletier A, Sceats L, Reynoso ED, Gonzalez SF, Graham DB, Chang J, Peters A, Woodruff M, Kim YA, Swat W, Morita T, Kuchroo V, Carroll MC, Kahn ML, Wucherpfennig KW, Turley SJ.: Podoplanin-rich stromal networks induce dendritic cell motility via activation of the C-type ectin receptor CLEC-2. Immunity 37(2): 276-89, Aug 2012.

Zheng X, Xu C, Smith AO, Stratman AN, Zou Z, Kleaveland B, Yuan L, Didiku C, Sen A, Liu X, Skuli N, Zaslavasky A, Chen M, Cheng L, Davis GE, Kahn ML. : Dynamic regulation of the cerebral cavernous malformation pathway controls vascular stability and growth. Developmental Cell 23(2): 342-55, Aug 2012.

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Last updated: 12/06/2013
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