Tomiauolo M, CN Matzko, I Poventud-Fuentes, JW Weisel, LF Brass and TJ Stalker. Interrelationships between structure and function during the hemostatic response to injury. Proc Natl Acad Sci USA 116(6):2243-2252, Feb 2019.

In a series of high resolution imaging studies, we explored in detail how a hemostatic plug comprised of platelets and fibrin forms in the setting of penetrating injuries in the macrovasculature. The results revealed a surprisingly heterogeneous hemostatic plug architecture, including gradients of platelet activation and spatial sequestration of thrombin activity outside of the vessel lumen. They also showed how a widely prescribed class of antiplatelet agents alters hemostatic plug architecture resulting in adverse bleeding in certain physiologic contexts.

Shen J, Sampietro S, Wu J, Tang J, Gupta S, Matzko CN, Tang C, Yu Y, Brass LF, Zhu L, Stalker TJ. Coordination of platelet agonist signaling during the hemostatic response in vivo. Blood Adv 1(27), Dec 2017.

Using a combination of genetic and pharmacologic approaches coupled with intravital imaging, these studies showed for the first time how thrombin, P2Y₁₂ and TxA₂ signaling are coordinated during development of a hierarchical organization of hemostatic plugs in vivo.  The findings provided novel insights into the impact of dual anti-platelet therapy on hemostasis and thrombosis.

Stalker TJ, Welsh JD, Tomaiuolo M, Wu J, Colace TV, Diamond SL, Brass LF.: A systems approach to hemostasis: 3. Thrombus consolidation regulates intrathrombus solute transport and local thrombin activity. Blood 124(11): 1824-31, Sept 2014.

In a series of three manuscripts published together in the same issue of Blood, we demonstrated that the physical properties of the accumulated mass of adherent platelets is critical in determining intrathrombus agonist distribution and platelet activation. We further defined a novel role for integrin signaling in the regulation of intrathrombus transport rates and localization of thrombin activity.

Stalker TJ, Traxler, EA, Wu, J, Wannemacher, KM, Cermignano, SL, Voronov, R, Diamond, SL, Brass, LF: Hierarchical organization in the hemostatic response and its relationship to the platelet-signaling network. Blood 121(10): 1875-85, Mar 2013.

This study was the first to describe how the hemostatic response produces a hierarchical structure in which a core of closely packed, irreversibly activated platelets is overlaid by a shell of loosely associated, minimally activated platelets. The reported studies demonstrated that variations in platelet activation in vivo arise through the integration of distinct elements of the platelet signaling network. We also determined how regional variations in the extent of platelet activation affect hemostatic plug stability and the passage of plasma-borne molecules within the platelet mass.