Mark L. Kahn, M.D.

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

Selected Publications

Goddard LM, Duchemin A-L, Ramalingan H, Wu B, Chen M, Bamezai S, Yang J, Li L, Morely M, Wang T, Scherrer-Crosbie M, Frank DB, Engleka KA, Jameson SC, Morrisey EE, Carroll TJ, Zhou B, Vermot J, Kahn ML: Hemodynamic forces sculpt developing heart valves through a KLF2-Wnt9b paracrine signaling axis. Developmental Cell 43(3): 274-289, Nov 2017.

Goddard LM, Kahn ML.: A BMPy Road for Venous Development Developmental Cell 42(5): 435-36, Sep 2017.

Tang Alan T, Choi Jaesung P, Kotzin Jonathan J, Yang Yiqing, Hong Courtney C, Hobson Nicholas, Girard Romuald, Zeineddine Hussein A, Lightle Rhonda, Moore Thomas, Cao Ying, Shenkar Robert, Chen Mei, Mericko Patricia, Yang Jisheng, Li Li, Tanes Ceylan, Kobuley Dmytro, Võsa Urmo, Whitehead Kevin J, Li Dean Y, Franke Lude, Hart Blaine, Schwaninger Markus, Henao-Mejia Jorge, Morrison Leslie, Kim Helen, Awad Issam A, Zheng Xiangjian, Kahn Mark L: Endothelial TLR4 and the microbiome drive cerebral cavernous malformations. Nature 545(7654): 305-310, May 2017 Notes: Covered in the NYT:

Welsh John D, Kahn Mark L, Sweet Daniel T: Lymphovenous hemostasis and the role of platelets in regulating lymphatic flow and lymphatic vessel maturation. Blood 128(9): 1169-73, Sep 2016.

Girard Romuald, Zeineddine Hussein A, Orsbon Courtney, Tan Huan, Moore Thomas, Hobson Nick, Shenkar Robert, Lightle Rhonda, Shi Changbin, Fam Maged D, Cao Ying, Shen Le, Neander April I, Rorrer Autumn, Gallione Carol, Tang Alan T, Kahn Mark L, Marchuk Douglas A, Luo Zhe-Xi, Awad Issam A: Micro-computed tomography in murine models of cerebral cavernous malformations as a paradigm for brain disease. Journal of Neuroscience Methods 271: 14-24, Sep 2016.

Cha Boksik, Geng Xin, Mahamud Md Riaj, Fu Jianxin, Mukherjee Anish, Kim Yeunhee, Jho Eek-Hoon, Kim Tae Hoon, Kahn Mark L, Xia Lijun, Dixon J Brandon, Chen Hong, Srinivasan R Sathish: Mechanotransduction activates canonical Wnt/β-catenin signaling to promote lymphatic vascular patterning and the development of lymphatic and lymphovenous valves. Genes & Development 30(12): 1454-69, Jun 2016.

Bui Hung M, Enis David, Robciuc Marius R, Nurmi Harri J, Cohen Jennifer, Chen Mei, Yang Yiqing, Dhillon Veerpal, Johnson Kathy, Zhang Hong, Kirkpatrick Robert, Traxler Elizabeth, Anisimov Andrey, Alitalo Kari, Kahn Mark L: Proteolytic activation defines distinct lymphangiogenic mechanisms for VEGFC and VEGFD. The Journal of Clinical Investigation 126(6): 2167-80, May 2016.

Zhou Z, Tang AT, Wong WY, Bamezai S, Goddard LM, Shenkar R, Zhou S, Yang J, Wright AC, Foley M, Arthur JS, Whitehead KJ, Awad IA, Li DY, Zheng X, Kahn ML: Cerebral cavernous malformations arise from endothelial gain of MEKK3-KLF2/4 signaling. Nature 532(7597): 122-6, April 2016.

Maltzman Jonathan S, Reed Hasina Outtz, Kahn Mark L: HA-ving lymphatics improves lung transplantation. The Journal of clinical investigation 125(11): 3999-4001, Nov 2015.

Sweet DT, Jiménez JM, Chang J, Hess PR, Mericko-Ishizuka P, Fu J, Xia L, Davies PF, Kahn ML: Lymph flow regulates collecting lymphatic vessel maturation in vivo. Journal of Clinical Investigation 125(8): 2995-3007, Aug 2015.

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Last updated: 10/15/2018
The Trustees of the University of Pennsylvania