Peter J. Newman, PhD

Peter J. Peter J. profile

Peter J. Newman, PhD

Jacquelyn Fredrick Endowed Chair for Foundational Research, Vice President for Research

Transfusion Medicine

Jacquelyn Fredrick Endowed Chair for Foundational Research
Vice President for Research and Associate Director

Versiti Blood Research Institute

Professor of Pharmacology and Cell Biology
Medical College of Wisconsin

Education and training

Doctoral Training
St. Louis University, PhD, 1983

Contact Information
  • 414-937-6237
  • 414-937-6237
  • Thrombosis, Hemostasis and Vascular Biology

    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:

    1. Build on recent crystallographic data of the PECAM-1 homophilic binding domain to define the molecular and structural determinants of PECAM-1-mediated cellular interactions. 
    2. Examine the structural and functional basis of allosteric regulation of PECAM-1 homophilic binding affinity.

    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:

    1. Exploiting recent advances in CRISPR/Cas9 gene editing technology to:
      • generate megakaryocyte progenitor cells, megakaryocytes, and platelets from induced pluripotent stem (iPS) cells to create platelet alloantigen-specific cell lines capable of long-term self-renewal, cryopreservation, and distribution.
      • Modifying genes encoding strategically selected cytosolic signaling molecules with the goal of improving the function and hemostatic effectiveness of iPSC-derived platelets and megakaryocytes.
    2. Using a recently developed novel humanized mouse model to conduct preclinical studies designed to evaluate th effectiveness of novel therapeutics to prevent or treat FNAIT.

    Grants

    • NIH R35 Outstanding Investigator Award (OIA) HL139937 (3/1/2018 - 2/28/2025) Basic Investigation and Translational Applications Concerning the Cell and Molecular Biology of Blood and Vascular Cells

    Huiying Zhi, MD
    Research Scientist II

    Nanyan Zhang, MD, PhD
    Research Scientist II

    Jesse Sundlov, PhD
    Postdoctoral Fellow

    Cathy Paddock 
    Senior Research Technologist

    Alyssa Moroi, PhD
    Research Scientist I

    Kathryn Williams
    Assistant Research Technologist

    Patents

    • Polymorphism of human platelet membrane glycoprotein IIIa and diagnostic and therapeutic applications thereof. Filed 04/27/1989 U.S. patent serial number 343,827. Japan patent application number 506,829. European PCT application number PCT-US90-02104. Issued February 25, 1992 as U.S. patent number 5,091,302.
    • Polymorphism of human platelet membrane glycoprotein IIb and diagnostic and therapeutic applications thereof. Filed 12/01/1989 U.S. patent serial number 433,946. Issued July 25, 1995 as U.S. patent number 5,436,163.
    • Platelet cell adhesion molecule and variants thereof. Filed 01/19/1990 U.S. patent serial number 466,140. European PCT application number PCT-US90-07418. Australian patent application number 71546/91. Japanese patent application number 32275/90. Issued November 23, 1993 as U.S. Patent Number 5,264,554.
    • Polynucleotides for determining the Pen polymorphism of human platelet membrane. Filed 07/01/1991 U.S. patent serial number 08/482,174. Issued July 14, 1998 as U.S. patent number 5,780,229. European PCT application number PCT-92914287.5 (0593572). 
    • Polymorphism of human platelet membrane glycoprotein IIIa and diagnostic and therapeutic applications thereof. Filed 11/22/1991. Divisional application covering non-human antibodies to PlA1 and PlA2 alloantigenic determinants. U.S. patent serial number 797,117. Issued February 21, 1995 as U.S. patent number 5,391,714.
    • Molecular basis of the human platelet Bra/Brb alloantigen system and applications thereof. Filed 06/30/1993. U.S. patent serial number 86,634. Issued May 14, 1996 as U.S. patent number 5,516,634.
    • Platelet-Endothelial Cell Adhesion Molecule-1 promoters and uses thereof. Filed 07/05/1994. U.S. patent serial number 08/270,985. European PCT application filed July 5, 1995. Issued September 16, 1997 as U.S. patent number 5,668,012.
    • Nucleic acids for the detection of the Bak polymorphism in human platelet membrane glycoprotein IIb. Filed 10/07/1994. U.S. patent serial number 319,946. Issued July 29, 1997 as U.S. patent number 5,652,357.
    • Polymorphism of human platelet membrane glycoprotein IIIa and diagnostic and therapeutic applications thereof. Filed 02/21/1995 U.S. patent serial number 392,363. Issued September 23, 1997 as U.S. patent number 5,670,337
    • Platelet cell adhesion molecule and variants thereof. Filed 06/07/1995 U.S. patent application number 08/478,210. Issued June 29, 1999 as U.S. patent number 5,917,030.
    • Methods and kits for determining the Pen polymorphism of human platelet membrane glycoprotein IIIa. Filed 07/01/1991. U.S. patent serial number 721,321. Issued October 26, 1999 as U.S. patent number 5,972,601.
    • Polynucleotides encoding Platelet Endothelial Cell Adhesion Molecule (PECAM-1) and fragments thereof. Filed 11/16/1994. US patent serial number 08/341,300. Issued February 1, 2000 as U.S. patent number 6,020,188.
    • Therapeutic use of Platelet Endothelial Cell Adhesion Molecule-1 Compositions. Filed 06/07/1995. U.S. patent application number 08/478,208. Issued July 11, 2000 as U.S. patent number 6,087,331.
    • Method to bioengineer Designer Platelets using CRISPR/Cas9 and stem cell methodologies. Filed 11/05/2014 as US Provisional Application 62/074,870, and on 11/03/15 as US Patent 14/931,321. Issued July 28, 2020 as U.S. patent number 10,725,041. 
    • A murine model of fetal/neonatal alloimmune thrombocytopenia. Filed 11/05/2019 as US Patent Application 16/674,804 (patent pending).
    • A method to bioengineer Designer Red Blood Cells using gene editing and stem cell methodologies. Filed 06/26/2020 as a U.S. Patent Application No. 16/913,741 (patent pending). 
     
    Thrombosis & Hemostasis
    We study the properties of blood that cause it to clot. Our findings help to treat diseases that cause blood clots or excessive bleeding.
     
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