Senior Investigator
Transfusion Medicine, Vascular Biology & Cell Therapy
Jacquelyn Fredrick Endowed Chair for Foundational Research
Professor
Departments of Pharmacology and Toxicology and Cell Biology, Neurobiology and Anatomy
Medical College of Wisconsin
Doctoral Training
St. Louis University, PhD, 1983
Our laboratory divides its attention between exploring the structure and function of PECAM-1 in the blood and vascular cells in which it is expressed and the generation of antigenically-distinct megakaryocytes and platelets from induced pluripotent stem (iPS) cells, and the use of a novel humanized mouse to examine the pathophysiology of platelet alloimmune disorders. Techniques range from CRISPR-mediated gene editing to protein crystallography to the development of animal models of platelet alloimmunity.
The Biology of PECAM-1: PECAM-1 (also known as CD31) is a cellular adhesion and signaling receptor comprised of six extracellular immunoglobulin (Ig) - like homology domains, a short transmembrane domain, and a 118 amino acid cytoplasmic domain that becomes serine and tyrosine phosphorylated upon cellular activation. PECAM-1 expression is restricted to blood and vascular cells. In circulating platelets and leukocytes, PECAM-1 functions largely as an inhibitory receptor that, via regulated sequential phosphorylation of its cytoplasmic domain, limits cellular activation responses. PECAM-1 is also highly expressed at endothelial cell intercellular junctions, where it functions as a mechanosensor, as a regulator of leukocyte trafficking, and in the maintenance of endothelial cell junctional integrity. PECAM-1–PECAM-1 homophilic interactions mediated by N-terminal Ig domain 1 are required for border localization, and contribute importantly to steady-state endothelial cell barrier stability and to recovery of endothelial cell junctional integrity, both in vitro and in vivo, following inflammatory or hemostatic challenge. Current studies seek to:
Generation of alloantigen-specific “Designer Platelets” in mice and man for diagnostic and investigative use: Immune reactions to platelets, initiated either by transfusion or by pregnancy, are responsible for two serious immunopathogenic syndromes: Post-transfusion purpura and fetal/neonatal alloimmune thrombocytopenia (FNAIT). FNAIT is caused by maternal antibodies generated in response to paternally-inherited antigens present on fetal platelets that re-cross the placenta and bind to fetal and/or neonatal platelets, resulting in thrombocytopenia often serious enough to require transfusion, and in the most severe cases causing intracranial hemorrhage and intrauterine death. To develop a greater understanding of the etiology of platelet alloimmune disorders, and to develop novel reagents leading to greatly improved diagnostic testing, we are:
Huiying Zhi, MD
Research Scientist II
Nanyan Zhang, MD, PhD
Research Scientist II
Douglas Franklin
Assistant Research Technologist
Cathy Paddock
Senior Research Technologist
Alyssa Moroi, PhD
Research Scientist I
A complete list of my published work can be found in MyNCBI Bibiography using the following link: http://www.ncbi.nlm.nih.gov/sites/myncbi/peter.newman.1/bibliography/41153642/public/?sort=date&direction=ascending.