Manasa Nayak, PhD, research assistant professor in Hematology, Oncology and Blood & Marrow Transplantation, was a finalist for the American Heart Association’s (AHA’s) Kenneth M. Brinkhous Early Career Investigator Prize in Thrombosis. The AHA recognized Nayak, a member of the Chauhan Lab, as one of four young investigators performing fundamental and significant research in thrombosis. Nayak presented his work during the AHA’s Vascular Discovery: From Genes to Medicine 2024 Scientific Sessions conference last week in Chicago.
Nayak’s talk was titled “Pyruvate kinase M2 (PKM2) regulates SNAP23-mediated platelet granule excocytosis, neutrophil cellular traps (NETs) formation and experimental venous thrombosis (VT).” PKM2 is a key enzyme that catalyzes the final step of glycolysis, producing energy for the body. PKM2 exists as tetramers and dimers. Dimeric PKM2, also has a non-glycolytic role because of its protein kinase activity to phosphorylate various protein targets, in addition to regulating aerobic glycolysis. In a recent publication in Blood, Nayak and his colleagues showed that dimeric PKM2 is upregulated in activated platelets. By targeting dimeric PKM2, the researchers inhibited agonist-induced platelet activation and aggregation in vitro in humans and mice. In addition, platelet specific PKM2 knock-out mice were less susceptible to arterial thrombosis in vivo without altering hemostasis.
Nayak’s present study shows that both genetic deletion of PKM2 and pharmacological inhibition of PKM2 dimerization reduces susceptibility to acute VT in the inferior vena cava stenosis model. Dimeric PKM2 enables the formation of NETs in acute VT most likely by upregulating SNAP23 phosphorylation and PF4 secretion from platelets. These novel findings make PKM2 a potential therapeutic target for not only arterial but also for acute venous thrombosis.
For this discovery, Nayak received a plaque and thanked his mentor, Anil Chauhan, MTech, PhD, and all the lab members those who were involved in the study. Chauhan is a professor in Hematology, Oncology and Blood & Marrow Transplantation, and received the Brinkhous award in 2011.
In addition to his research team, Nayak is grateful for the support of his wife, Jayashree, his Aunt Rambhamani, his parents, and the rest of his family.
