Mark L. Kahn, M.D.

faculty photo
Edward S. Cooper, M.D./Norman Roosevelt and Elizabeth Meriwether McLure Professor
Department: Medicine

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
B.A. (Biology)
Brown University, 1984.
M.D. (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.

Description of Clinical Expertise

general cardiology

Selected Publications

Sung DC, Chen X, Chen M, Yang J, Schultz S, Babu A, Xu Y, Gao S, Keller TCS 4th, Mericko-Ishizuka P, Lee M, Yang Y, Scallan JP, Kahn ML.: VE-cadherin enables trophoblast endovascular invasion and spiral artery remodeling during placental development, Elife 11(e77241), Apr 2022.

Keller IV TCS, Lim L, Shewale S, McDaid K, Marti-Pamies I, Tang AT, Wittig C, Guerrero AA, Sterling S, Leu NA, Scherrer-Crosbie M, Gimotty PA, and Kahn, ML: Genetic Blockade of Lymphangiogenesis does not Impair Cardiac Function after Myocardial Infarction. Journal of Clinical Investigation August 2021.

Snellings DA, Hong CC, Ren AA, Lopez-Ramirez MA,Girard R, Srinath A, Marchuk DA, Ginsberg MH, Awad IA, Kahn ML : Cerebral Cavernous Malformation: From Mechanism to Therapy Circulation Research 129(1): 195-215, Jun 2021.

Ren AA, Snellings DA, Su SY, Hong CC, Castro M, Tang AT, Detter MR, Hobson N, Girard R, Romanos S, Lightle R, Moore T, Shenkar R, Benavides C, Beaman MM, Helge Mueller-Fielitz H, Chen M, Mericko P, Yang J, Sung DC, Lawton MT, Ruppert M, Schwaninger M, Körbelin J, Potente M, Awad IA, Marchuk DA and Kahn ML: PIK3CA and CCM mutations fuel cavernomas through a cancer-like mechanism. Nature 594(7862): 271-276, Jun 2021.

Stratman AN, Burns MC, Farrelly OM, Davis AE, Li W, Pham VN, Castranova D, Yano JJ, Goddard LM, Nguyen O, Galanternik MV, Bolan TJ, Kahn ML, Mukouyama YS, Weinstein BM: Chemokine mediated signalling within arteries promotes vascular smooth muscle cell recruitment. Communications Biology Dec 2020.

Hong CC, Tang AT, Detter MR, Choi JP, Wang R, Yang X, Guerrero AA, Wittig CF, Hobson N, Girard R, Lightle R, Moore T, Shenkar R, Polster SP, Goddard LM, Ren AA, Leu NA, Sterling S, Yang J, Li L, Chen M, Mericko-Ishizuka P, Dow LE, Watanabe H, Schwaninger M, Min W, Marchuk DA, Zheng X, Awad IA, Kahn ML, : Cerebral cavernous malformation are driven by ADAMTS5 proteolysis of versican. The Journal of Experimental Medicine Oct 2020.

Nicolson PL, Welsh JD, Chauhan A, Thomas MR, Kahn ML, Watson SP: A rationale for blocking thromboinflammation in COVID-19 with Btk inhibitors. Platelets 31(5): 685-690, Jul 2020.

Betterman KL, Sutton DL, Secker GA, Kazenwadel J, Oszmiana A, Lim L, Miura N, Sorokin L, Hogan BM, Kahn ML, McNeill H, Harvey NL.: Atypical cadherin FAT4 orchestrates lymphatic endothelial cell polarity in response to flow. Journal of Clinical Investigation June 2020.

Polster SP, Sharma A, Tanes C, Tang AT, Mericko P, Cao Y, Carrión-Penagos J, Girard R, Koskimäki J, Zhang D, Stadnik A, Romanos SG, Lyne SB, Shenkar R, Yan K, Lee C, Akers A, Morrison L, Robinson M, Zafar A, Bittinger K, Kim H, Gilbert JA, Kahn ML, Shen L, Awad IA: Permissive microbiome characterizes human subjects with a neurovascular disease cavernous angioma. Nature Communications May 2020.

Welsh JD, Hoofnagle MH, Bamezai S, Oxendine M, Lim L, Hall JD, Yang J, Schultz S, Engel JD, Kume T, Oliver G, Jimenez JM, Kahn ML: Hemodynamic regulation of perivalvular endothelial gene expression prevents deep venous thrombosis. The Journal of Clinical Investigation Dec 2019.

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Last updated: 12/06/2022
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