CVI Program Unit Administrator:
Thrombosis / Hemostasis
mechanisms of thrombosis
platelets, coagulation, vascular biology, signal transduction, systems biology, proteomics, transgenic mice, megakaryocytes, intravital microscopy.
Description of Research
My longstanding research and clinical interest is in platelet biology and the mechanisms of platelet activation in response to vascular injury and disease. Platelets are blood cells best known for their role in halting bleeding after vascular injury, but they do many other things as well, not all of which are healthy for humans. People that lack platelets are at risk for life-threatening bleeding. People that have platelets are at risk for the kinds of acute arterial thrombosis that leads to heart attacks and strokes, especially in the setting of atherosclerotic cardiovascular disease. Our goal is to understand the former and prevent the latter. The work we are doing focuses on human biology and pathology, but makes extensive use of genetically engineered mouse models and systems biology approaches as well. Studies currently funded by the NIH Heart, Lung and Blood Institute (NHLBI) and the American Heart Association include efforts to understand how platelet activation is initiated and regulated, how contacts between activated platelets foster thrombus growth and stability, in part by establishing a protected local environment, and how differences among platelets affect responses to injury. Methods that we employ range from the manipulation of gene expression in megakaryocytes to intravital high resolution confocal microscopy and computerized modeling. Campus collaborations include strong links to the School of Engineering and to investigators in the Departments of Medicine, Pediatrics and Pharmacology. Potential rotation and thesis projects can be identified in any of these areas.
Lab Rotation Topics
Changing all the time, so if this area of investigation sounds interesting to you, come by for a chat.
Current Laboratory Personnel (February 2012):
Timothy J. Stalker, PhD - Research Assistant Professor
Peisong Ma, PhD - Senior Research Investigator
Ken Wannemacher, PhD - Postdoctoral Investigator
Maurizio Tomaiuolo, PhD - Postdoctoral Investigator
Jie Wu - Research Specialist
Hong Jiang - Research Specialist
Darci Foote - Penn Vagelos Scholar (2012)
Leo Wang - Penn Vagelos Scholar (2012)
Angel Chen - Penn Vagelos Scholar (2015)
M.U. Naik, T.J. Stalker, L.F. Brass and U.P. Naik: JAM-A protects from thrombosis by suppressing integrin αIIbβ3-dependent outside-in signaling in platelets. Blood 2012, in press.
P. Ma, A. Cierniewska, R. Signarvic, M. Cieslak, H. Kong, A.J. Sinnamon, R.R. Neubig, D.K. Newman, T.J. Stalker and L.F. Brass: A newly identified complex of spinophilin and the tyrosine phosphatase, SHP-1, modulates platelet activation by regulating G protein-dependent signaling. Blood 119(8): 1935-1945, Feb 23 2012.
D. Lee, K.P. Fong, M.R. King, L.F. Brass and D.A. Hammer: Differential dynamics of platelet contact and spreading. Biophys. J. 102(3): 472-482, Feb 8 2012.
A.A. Schmaier, T.J. Stalker, J.J. Runge, D. Lee, C. Nagaswami, P. Mericko, M. Chen, S. Cliché, C. Gariepy, L.F. Brass, D.A. Hammer, J.W. Weisel, K. Rosenthal and M.L. Kahn: Occlusive thrombi arise in mammals but not birds in response to arterial injury: evolutionary insight into human cardiovascular disease. Blood 118(13): 3661-3669, Sep 29 2011.
L.F. Brass, K.M. Wannemacher, P. Ma and T.J. Stalker: Regulating thrombus growth and stability to achieve an optimal response to injury. J. Thromb. Haemost. 9 (Suppl.1): 66-75, Jul 2011.
K.P. Fong, C. Barry, A.N. Tran, E.A. Traxler, K.M. Wannemacher, H.-Y. Tang, K.D. Speicher, I.A. Blair, D.W. Speicher, T. Grosser and L.F. Brass: Deciphering the human platelet sheddome. Blood 117(1): e15-e26, Jan 6 2011.
K.M. Wannemacher, L. Wang, L. Zhu, and L.F. Brass: The role of semaphorins and their receptors in platelets: lessons learned from neuronal and immune synapses. Platelets 22(6): 461-465, 2011.
K.M. Wannemacher, L. Zhu, H. Jiang, K.P. Fong, T.J. Stalker, D. Lee, A.N. Tran, K.B. Neeves, S. Maloney, A. Kumanogoh, H. Kikutani, D.A. Hammer, S.L. Diamond and L.F. Brass: Diminished contact-dependent reinforcement of Syk activation underlies impaired thrombus growth in mice lacking Semaphorin 4D (Sema4D). Blood 116(25): 5707-5715, Dec 16 2010
R.S. Signarvic, A. Cierniewska, T.J. Stalker, K.P Fong, M.S. Chatterjee, P.R. Hess, P. Ma, S.L. Diamond, R.R. Neubig and L.F. Brass: RGS/Gi2α interactions modulate platelet accumulation and thrombus formation at sites of vascular injury. Blood 116(26): 6092-6100, Dec 23 2010.
M. Chatterjee, J. Purvis, L.F. Brass and S.L. Diamond: Pairwise agonist scanning of human platelets reveals the high-dimensional calcium response to combinatorial mediators of thrombosis. Nature Biotechnology 28(7): 727-732, Jul 2010.
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Last updated: 03/28/2012
The Trustees of the University of Pennsylvania