WELCOME
Our research is aimed at understanding the development and function of blood platelets. These tiny, numerous cells initiate and co-ordinate blood clotting (i.e. hemostasis) at wound sites by adhering, aggregating and secreting a wide assortment of molecules. Platelets are also involved in the formation of arterial plaques and pathological clots such as the thrombi that cause heart attacks and strokes, major causes of mortality in the modern world. Many of our insights into the mechanisms of platelet development and function have come from studies of patients with inherited platelet disorders. Our particular interest is alpha granules, secretory vesicles that platelets use to transport and secrete several hundred different kinds of protein. We have identified several proteins and cellular pathways involved in the development of alpha granules in the cells that produce platelets, the bone marrow megakaryocytes.
PAST RESEARCH HIGHLIGHTS
Discovery of the genetic basis of Gray Platelet Syndrome. Preview
Identification of VPS16B, binding partner of VPS33B, as essential for alpha granule biogenesis. Read the paper. Accompanying editorial.
Establishment of the Nbeal2 knockout mouse model of GPS – insights into its role in platelet development. Read the paper. Accompanying editorial.
Selected recent highlights
Nature Genetics 47,535–538 (2015): Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia.
FlnA binding to PACSIN2 F-BAR domain regulates membrane tubulation in megakaryocytes and platelets. Accompanying editorial.
Inside Blood Editorial: Platelet Production – New Players in the Field
Arteriosclerosis Thrombosis and Vascular Biology Jun;36(6):1164-73 (2016): Intracellular Trafficking, Localization and Mobilization of Platelet-Borne Thiol Isomerases. Editor’s choice free access. Accompanying editorial.
Blood Jun 9;127(23):2791-803 (2016) Plenary paper: A high-throughput sequencing test for diagnosing inherited bleeding, thrombotic, and platelet disorders. Accompanying editorial.
Nature Communications 2017 April 3;8:4816: Loss of the Arp2/3 complex component ARPC1B causes platelet abnormalities and predisposes to inflammatory disease.
News Coverage: SickKids, Canadian Press CBC: Website Lead Story, The National April 3, 2017
Arteriosclerosis Thrombosis and Vascular Biology https://doi.org/10.1161/ATVBAHA.118.311270 NBEAL2 (Neurobeachin-Like 2) Is Required for Retention of Cargo Proteins by α-Granules During Their Production by Megakaryocytes
Editorial: https://doi.org/10.1161/ATVBAHA.118.311614 Unlocking the Molecular Secrete(s) of α-Granule Biogenesis
Blood 2020 Aug 6;136(6):715-725. doi: 10.1182/blood.2019004276 The endoplasmic reticulum protein SEC22B interacts with NBEAL2 and is required for megakaryocyte α-granule biogenesis
Visit PubMed for a full list of publications.
Contact information:
Walter H.A. Kahr, MD, PhD, FRCPC
Division of Haematology/Oncology
Senior Scientist, Program in Cell Biology
PGCRL Rm 19.9714
686 Bay Street
Toronto, ON, M5G 0A4
CANADA
Our funding partners:
