Peter Newman Portrait

Peter J. Newman, PhD

 
Vice President for Research
BloodCenter of Wisconsin
 
Associate Director
Blood Research Institute
 
Professor
Department of Pharmacology
Department of Cell Biology, Neurobiology, and Anatomy
Medical College of Wisconsin
 
Education and training
Doctoral Training
St. Louis University, PhD, 1983
 
Contact information
Phone: (414) 937-6237
Fax: (414) 937-6284

Thrombosis, Hemostasis and Vascular Biology
Central to the ability of vascular cells to adhere to the extracellular matrix and to each other is an abundant supply of cell surface adhesion molecules that, in addition to influencing the adhesive phenotype of the cell, are also capable of transmitting signals into, and responding to signals from, the cell interior (often referred to an outside/in and inside/out signal transduction, respectively). Such post-ligand events occur by virtue of the ability of these transmembrane proteins to interact with intracellular kinases and phosphatases, G-proteins, adapter proteins, and cytoskeletal components. Our laboratory divides its attention between exploring the role of stimulatory and inhibitory receptors in regulating adhesion and aggregation of human and murine platelets (funded through a Program Project grant), and the structure and function of PECAM-1 in the blood and vascular cells in which it is expressed (funded through a long-standing R01). Techniques range from biochemistry to molecular biology to whole animal models of thrombosis and hemostasis.

Grants
  • NIH Grant R01 HL40926, years 22-26 - Molecular Biology and Function of PECAM-1
  • NIH Program Project Grant P01 HL44612, years 21-25 (Program Director, Leader, Project 1, and Director of Administrative Core A) - Molecular Mechanisms of Platelet Activation and Adhesion
  • NIH Postdoctoral Training Grant T32 HL07209 (Co-PI with GC White)
Ongoing NIH-Funded Research Projects
  • Molecular mechanisms of integrin signaling
  • Integrin/ITAM coupling in platelets and vascular cells
  • Role of PECAM-1 adhesion and signaling in endothelial cell barrier function and vascular permeability
  • Construction of transgenic and knock-in mice expressing variant forms of PECAM-1
  • In vitro microfluidic models of thrombus formation

Cunji Gao, MD, PhD
Research Scientist I
 
Huiying Zhi, MD

Research Scientist I
 
Nanyan Zhang, MD, PhD
Research Scientist I

Heng Mei, MD
Postdoctoral Fellow
 
Cathy Paddock

Sr. Research Technologist
 
Marjorie Kipp

Research Technologist

Newman Lab Group_Photo
















 

Selected Publications
  • Baldassare JJ, RA Kahn, MA Knipp, and PJ Newman: Reconstitution of platelet proteins into phospholipid vesicles: Functional proteoliposomes. J Clin Invest 1985, 75:35-39.
  • Newman PJ, J Gorski, GC White II, S Gidwitz, CJ Cretney, and RH Aster: Enzymatic amplification of platelet-specific messenger RNA using the polymerase chain reaction. J. Clin. Invest 1988, 82:739-743.
  • Newman PJ, R Derbes, and RH Aster: The human platelet alloantigens, PlA1 and PlA2, are associated with a Leucine33/Proline33 amino acid polymorphism in membrane glycoprotein IIIa, and are distinguishable by DNA typing. J Clin Invest 1989, 83:1778-1781.
  • Newman PJ, MC Berndt, J Gorski, GC White II, SL Lyman, C Paddock, and WA Muller: PECAM-1 (CD31): Cloning and relation to adhesion molecules of the immunoglobulin gene superfamily. Science 1990, 247:1219-1222.
  • Newman PJ, U Seligsohn, S Lyman, M Poncz, and BS Coller: The molecular genetic basis of Glanzmann's thrombasthenia in the Iraqi-Jewish and Arab populations in Israel. Proc Natl Acad Sci (USA) 1991, 88:3160-3164.
  • Jackson DE, CM Ward, R Wang, and PJ Newman: The protein tyrosine phosphatase SHP-2 binds Platelet/Endothelial Cell Adhesion Molecule-1 (PECAM-1) and forms a distinct signaling complex during platelet aggregation: Evidence for a mechanistic link between PECAM-1 and integrin-mediated signal transduction. J. Biol Chem 272:6986-6993, 1997.
  • Wang R, SJ Shattil, DR Ambruso, and PJ Newman: Truncation of the cytoplasmic domain of β3 in a variant form of Glanzmann thrombasthenia abrogates signaling through the αIIbβ3 complex. J Clin Invest 100:2393-2403, 1997.
  • Patil S, DK Newman, and PJ Newman: PECAM-1 serves as an inhibitory receptor that modulates platelet responses to collagen. Blood 97:1727-1732, 2001. PMID: 11238114
  • Gao C, W Sun, M Christofidou-Solomidou, M Sawada, DK Newman, C Bergom, SM Albelda, S Matsuyama, and PJ Newman: PECAM-1 functions as a specific and potent inhibitor of mitochondrial-dependent apoptosis. Blood 102:169-179, 2003. PMID: 12649141
  • Rathore V, MA Stapleton, CA Hillery, RR Montgomery, TC Nichols, EP Merricks, DK Newman, and PJ Newman: PECAM-1 negatively regulates GPIb/V/IX signaling in murine platelets. Blood 102:3658-3664, 2003. PMID: 12893757
  • Boylan, B, H Chen, V Rathore, C Paddock, M Salacz, KD Friedman, BR Curtis, M Stapleton, DK Newman, and PJ Newman: Anti-GPVI-associated ITP: An acquired platelet disorder caused by autoantibody-mediated clearance of the GPVI/FcRγ-chain complex from the human platelet surface. Blood 104:1350-1355, 2004. PMID: 15150079
  • Maas M, MA Stapleton, CR Bergom, DL Mattson, DK Newman, and PJ Newman: Endothelial PECAM-1 confers protection against endotoxic shock. Am J Physiol Heart Circ Physiol 288:H159-H164, 2005. PMID: 15319204
  • Falati S, S Patil, PL Gross, M Stapleton, G Merrill-Skoloff, NE Barrett, KL Pixton, H Weiler, B Cooley, DK Newman, PJ Newman, BC Furie, B Furie, and JM Gibbins: Platelet PECAM-1 inhibits thrombus formation in vivo. Blood 107:535-541, 2006. PMID: 16166583
  • Novinska M, BC Pietz, TM Ellis, DK Newman, and PJ Newman: The alleles of PECAM-1. Gene 376:95-101, 2006. PMID: 16581204
  • Boylan B, MC Berndt, ML Kahn, and PJ Newman: Activation-independent, antibody-mediated removal of GPVI from circulating human platelets: Development of a novel NOD/SCID mouse model to evaluate the in vivo effectiveness of anti-human platelet agents. Blood 108:908-914, 2006. PMID: 16569773
  • Bergom C, R Goel, C Paddock, C Gao, DK Newman, S Matsuyama, and PJ Newman: The cell-adhesion and signaling molecule PECAM-1 is a molecular mediator of resistance to genotoxic chemotherapy. Cancer Biology & Therapy 5:1699-1707, 2006. PMID: 17106245
  • Zhu J, B Boylan, B-H Luo, PJ Newman and TA Springer: Tests of the extension and dead-bolt models of integrin activation. J Biol Chem 282, 11914-11920, 2007. PMID 17301049
  • Boylan B, C Gao, V Rathore, JC Gill, Debra K. Newman, and PJ Newman: Identification of FcγRIIa as the ITAM-bearing receptor mediating αIIbβ3outside-in integrin signaling in human platelets. Blood 112:2780-2786, 2008. PMCID: PMC2556613
  • Newman PJ and DK Newman: Platelets and the Vessel Wall In Nathan and Oski's Hematology of Infancy and Childhood (7th Edition). Elsevier Press, pp. 1379-1398, 2008.
  • Goel R, B Schrank, S Arora, B Boylan, B Fleming, H Miura, PJ Newman, RC Molthen, and DK Newman: Site-specific effects of PECAM-1 on atherosclerosis in LDL receptor-deficient mice. Arterioscler Thromb Vasc Biol 28:1996-2002, 2008. PMID: 18669884
  • Bakchoul T, B Boylan, UJH Sachs, G Bein, C Ruan, S Santoso, and PJ Newman: Blockade of maternal anti-HPA-1a-mediated platelet clearance by an HPA-1a epitope-specific F(ab')2 in an in vivo mouse model of alloimmune thrombocytopenia. Transfusion 49:265-270, 2009. PMID: 19000229
  • Gao C, B Boylan, D Bougie, JC Gill, J Birenbaum, DK Newman, RH Aster, and PJ Newman: Eptifibatide-induced thrombocytopenia and thrombosis in humans require FcγRIIa and the integrin β3 cytoplasmic domain. J Clin Invest 119:504-511, 2009. PMCID: PMC2648674
  • Privratsky JR, BE Tourdot, DK Newman, and PJ Newman: The anti-inflammatory actions of PECAM-1 do not involve regulation of endothelial cell NFκB. J Immunol 184: 3157-63, 2010.
  • Crockett J, DK Newman, and PJ Newman: PECAM-1 is a negative regulator of laminin-induced platelet activation. J Thromb Haemost 8:1584-1593, 2010.
  • Privratsky JR, C Paddock, and PJ Newman: Relative contribution of PECAM-1-mediated adhesion and signaling to the maintenance of vascular integrity. J Cell Sci 124:1477, 2011.
  • Gao C, B Boylan, J Fang, DA Wilcox, DK Newman, and PJ Newman: Heparin promotes platelet responsiveness by potentiating αIIbβ3-mediated outside-in signaling. Blood 117:4946, 2011.
  • Paddock, CA, B Lytle, F Peterson, T Holyst, PJ Newman, B Volkman, and DK Newman. Residues within a lipid-associated segment of hte PECAM-1 cytoplasmic domain are susceptible to inducible, sequential phosphorylation. Blood 117:6012-6023, 2011.

Patents
  • Polymorphism of human platelet membrane glycoprotein IIIa and diagnostic and therapeutic applications thereof. Filed 4/27/89 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 12/01/89 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 01/19/90 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 07/1/91 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). Notice of allowance in Europe received 4/24/97. U.S. divisional (149 case) covering methods and kits is pending.
  • Polymorphism of human platelet membrane glycoprotein IIIa and diagnostic and therapeutic applications thereof. Filed 11/22/91. 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 6/30/93. 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 7/5/94. Patent covering the human PECAM-1 promoter and vectors that use it to drive transcription. 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 10/7/94. 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 2/21/95 Divisional application covering oligonucleotides to detect the PlA1 and PlA2 alleles of GPIIIa, and peptides used to make PIA - specific atnibodies. 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 06/07/95.U.S. patent application number 08/478,210. One claim covering sense and anti-sense oligonucleotide probes to any region of PECAM-1 cDNA. 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 07/01/91. U.S. patent serial number 721,321. Twenty-seven claims covering DNA typing and non-human antibody-based tying for the Pena and Penb epitopes on GPIIIa. 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 11/16/94. US patent serial number 08/341,300. Ten claims covering cDNAs encoding full-length PECAM-1, the extracellular domain of PECAM-1, and subsets thereof. Issued February 1, 2000 as U.S. patent number 6,020,188.
  • Therapeutic use of Platelet Endothelial Cell Adhesion Molecule-1 Compositions. Filed 06/07/95. U.S. patent application number 08/478,208. Twelve claims covering methods for using soluble PECAM-1 to modulate angiogenesis, relieve inflammation, and inhibit arterial occlusions associated with atherosclerosis or vascular trauma. Issued July 11, 2000 as U.S. patent number 6,087,331.

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