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Adults (18-65), Geriatrics (65+)
Adults (18-65), Geriatrics (65+)
Research InterestsSignaling pathways in angiogenesis and hemostasis. Key words: Angiogenesis, vascular development, platelet, signaling. Description of ResearchMy 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.
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 : 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 : 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 : 2019.
Tang Alan T, Sullivan Katie R, Hong Courtney C, Goddard Lauren M, Mahadevan Aparna, Ren Aileen, Pardo Heidy, Peiper Amy, Griffin Erin, Tanes Ceylan, Mattei Lisa M, Yang Jisheng, Li Li, Mericko-Ishizuka Patricia, Shen Le, Hobson Nicholas, Girard Romuald, Lightle Rhonda, Moore Thomas, Shenkar Robert, Polster Sean P, Roedel Claudia J, Li Ning, Zhu Qin, Whitehead Kevin J, Zheng Xiangjian, Akers Amy, Morrison Leslie, Kim Helen, Bittinger Kyle, Lengner Christopher J, Schwaninger Markus, Velcich Anna, Augenlicht Leonard, Abdelilah-Seyfried Salim, Min Wang, Marchuk Douglas A, Awad Issam A, Kahn Mark L: Distinct cellular roles for PDCD10 define a gut-brain axis in cerebral cavernous malformation. Science translational medicine 11 (520): 2019.
Tang, AT, Sullivan KR, Hong, CT, Goddard LM, Aparna M, Ren A, Pardo H, Peiper A, Griffin E, Tanes C, Mattei LM, Yang J, Li L, Mericko-Ishizuka P, Shen L, Hobson N, Girard R, Lightle R, Moore T, Shenkar R, Polster SP, Roedel CJ, Li N, Qin Z, Whitehead KJ, Zheng X, Akers A, Morrison L, Kim H, Bittinger K, Lenger CJ, Schwaninger M, Velcich A, Augenlicht L, Abdelilah-Seyfried S, Min W, Marchuk D, Awad IA, Kahn ML: Distinct cellular roles for PDCD10 define a gut-brain axis in cerebral cavernous malformation Translational Medicine : 2019.
Pawlak John B, Bálint László, Lim Lillian, Ma Wanshu, Davis Reema B, Benyó Zoltán, Soares Michael J, Oliver Guillermo, Kahn Mark L, Jakus Zoltán, Caron Kathleen M: Lymphatic mimicry in maternal endothelial cells promotes placental spiral artery remodeling. The Journal of clinical investigation 129 (11): 4912-4921,2019.
Lim Lillian, Bui Hung, Farrelly Olivia, Yang Jisheng, Li Li, Enis David, Ma Wanshu, Chen Mei, Oliver Guillermo, Welsh John D, Kahn Mark L: Hemostasis stimulates lymphangiogenesis through release and activation of VEGFC. Blood 134 (20): 1764-1775,2019.
Welsh John D, Hoofnagle Mark H, Bamezai Sharika, Oxendine Michael, Lim Lillian, Hall Joshua D, Yang Jisheng, Schultz Susan, Engel James Douglas, Kume Tsutomu, Oliver Guillermo, Jimenez Juan M, Kahn Mark L: Hemodynamic regulation of perivalvular endothelial gene expression prevents deep venous thrombosis. The Journal of clinical investigation : 2019.
Reed Hasina Outtz, Wang Liqing, Kahn Mark L, Hancock Wayne W: Donor-Host lymphatic anastomosis after murine lung transplantation. Transplantation : 2019.
Tang Alan T, Kahn Mark L: Why Don't Cerebral Cavernous Malformations Go With the Flow? Circulation research 125 (10): 871-873,2019.
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