Modulation of Hemostasis & Thrombosis
The Brown lab’s hemostasis research focuses on developing therapeutics for hemorrhage (uncontrolled bleeding), one of the greatest challenges in emergency medicine. Traditional treatments rely heavily on donor platelet transfusions, which suffer from short shelf-lives, high contamination risks, and limited availability in rural or battlefield settings. To address this, the Brown Lab has developed Platelet-Like Particles (PLPs), which are synthetic, microgel-based mimics that augment the body’s natural clotting process.
Nellenbach, K., Mihalko, E., Nandi, S., Koch, D. W., Shetty, J., Moretti, L., Sollinger, J., Moiseiwitsch, N., Sheridan, A., Pandit, S., Hoffman, M., Schnabel, L. V., Lyon, L. A., Barker, T. H., & Brown, A. C. (2024). Ultrasoft platelet-like particles stop bleeding in rodent and porcine models of trauma. Science Translational Medicine, 16(742). https://doi.org/10.1126/scitranslmed.adi4490
Unlike passive sealants, these PLPs are engineered to be “smart” and highly selective. They are functionalized with fibrin-specific fragments that allow them to circulate inertly in the bloodstream until they encounter an injury site. Once they identify a forming clot, they bind to the fibrin mesh and physically promote clot contraction, mimicking the mechanical action of natural platelets. This research bridges the gap between materials science and clinical trauma care, providing a stable, off-the-shelf solution to stabilize patients during the “golden hour” following a traumatic injury.
The Brown lab also develops clot-targeted Fibrin-Specific Nanogels (FSNs) designed to treat conditions like thromboinflammation and deep vein thrombosis (DVT). These nanogels serve as sophisticated delivery vehicles, carrying potent “clot-busting” drugs directly to an obstruction while shielding the rest of the body from systemic side effects.
Anastasia Sheridan, Kimberly Nellenbach, Sanika Pandit, Elizabeth Byrnes, Grace Hardy, Halle Lutz, Nina Moiseiwitsch, Grant Scull, Emily Mihalko, Jerrold H. Levy, and Ashley C. Brown. Clot-Targeted Nanogels for Dual-Delivery of AntithrombinIII and Tissue Plasminogen Activator to Mitigate Disseminated Intravascular Coagulation Complications. ACS Nano 2024 18 (24), 15517-15528. DOI: 10.1021/acsnano.4c00162