Peter J. Newman, Ph.D.

Vice President for Research

BloodCenter of Wisconsin

Associate Director, Blood Research Institute

Professor

Depts. of Pharmacology and Cell Biology

Medical College of Wisconsin
Associate Director, Cardiovascular Research Center

Doctoral Training
Ph.D., St. Louis University, 1983

Grant Support
Ongoing Research Projects
Selected Publications
Invited Lectures
Patents
Laboratory Staff
Contact Information

Research Interests

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.

Current Grant Support

• NIH Grant R01 HL40926, years 22-26 - Molecular Biology and Function of PECAM-1
• NIH Program Project Grant P01-HL44612, years 16-20 (Program Director, Leader, Project 1, and Director of Administrative Core A) - Molecular Mechanisms of Platelet Activation and Adhesion
• NIH Postdoctoral Training Grant HL-07209 (Co-PI with GC White)

Ongoing NIH-funded research projects are listed below:

• 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

 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, Pl^A1 and Pl^A2, 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 α_IIbβ₃  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 α_IIbβ₃outside-in integrin signaling in human platelets. Blood 112:2780-2786, 2008. PMCID: PMC2556613
• 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

Invited Lectures (since 2007)

• Plenary Lecture - 51^st Annual Meeting of the German Society of Thrombosis and Haemo-stasis Research - Dresden, Germany - (2/23/07) - “Function of PECAM-1 in murine and human platelets”.
• Hematology Grand Rounds - University of Washington - Seattle, Washington – (6/15/07) “Murine and human antibodies to platelet membrane glycoprotein VI: Clinical insult and therapeutic applications”.
• International Society on Thrombosis and Hemostasis – State-of-the-Art Lecture – Geneva, Switzerland - (7/10/07) - “Models to evaluate anti-platelet agents”.
• Emil von Behring Award Lecture – Deutschen Gesellschaft für Transfusionsmedizin und Immunhämatologie – Friedrichshafen, Germany – (9/18/07) – “Human platelet alloanti-gens – A personal odyssey”
• Invited Seminars at Osaka University Hospital – Osaka, Japan – (10/30/07); Tokai University School of Medicine – Isehara, Japan – (11/5/07); Keio University School of Medicine – Tokyo, Japan - (11/6/07) “Murine and human antibodies to platelet membrane glycoproteins: Applications for interrogating platelet function and survival”.
• Plenary Lecture – Protein Research Institute Symposium on Current Topics on Cellular Control Mechanisms Mediated by Adhesion Receptors – Osaka, Japan – (10/31/07) – “Activating and inhibitory receptors that regulate platelet responses”.
• Invited Seminar – Novo Nordisk – East Brunswick, NJ - (1/31/2008) – “Molecular mech-anisms of platelet activation and adhesion”
• Invited Seminar - Clinical Institute for Medical and Chemical Laboratory Diagnosis, Medical University of Vienna - Vienna, Austria – (2/19/08) – “The biology of the platelet GPVI collagen receptor: basic and clinical applications”. 
• Invited Speaker - Platelets 2008 - Woods Hole, MA - (10/16/08) - “Molecular mechanisms of platelet activation and adhesion”.
• Russell Ross Memorial Lecture in Vascular Biology – American Heart Association Scientific Sessions – New Orleans, LA - (11/10/08) - “Activating and inhibitory receptors in blood and vascular cells”.
• Plenary Lecture – 31st Congress of the Japanese Society on Thrombosis and Hemostasis – Osaka, Japan - (11/20/08) - “Activating and inhibitory receptors in blood and vascular cells”.
• Keynote Speaker – (1/9/09) – 1st Annual Cardiovascular Translational Research Symposium – Medical College of Wisconsin – Milwaukee, WI - “Paradoxical risks and rewards of using anti-platelet drugs to treat myocardial infarction – a molecular explanation”.
• Invited Seminar - University of Reading - Reading, England - (3/30/09) - “Integrin/ITAM connections in platelets”.
• Invited Seminar - University College Cork - Cork, Ireland - (4/3/09) - "Integrin/ITAM connections in platelets".
• Invited Seminar - Biomedical Diagnostics Institute (BDI) - Dublin, Ireland – (4/7/09) "Paradoxical risks and rewards of using anti-platelet drugs to treat myocardial infarction: a molecular explanation".
• The ETS Walton Visiting Professor Public Lecture - Dublin, Ireland - (4/15/09) "Thrombosis, novel insights in molecular regulation of platelet function".
• Invited Seminar - Regenerative Medicine Institute and National Centre for Biomedical Engineering Science, National University of Ireland - Galway, Ireland - (4/16/09) "Integrin/ITAM connections in platelets"
   

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 Pl^A1 and Pl^A2 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 Br^a/Br^b 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 Pl^A1 and Pl^A2 alleles of GPIIIa, and peptides used to make PI^A - 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.

 Laboratory Staff (2010)

 From left: Deb Newman (Investigator), Deb Schaller (Admin Asst), Maya Bates (Undergraduate Student), Michelle Brenner (Research Technologist), Marge Kipp (Animal Technologist), Ben Tourdot (Graduate Student), Chris Kuckelburg (Postdoctoral Fellow), Cathy Paddock (Sr. Research Technologist), Jimmy Crockett (Postdoctoral Fellow), Peter Newman (Sr. Investigator), Ben Andrew (Research Technologist), Taisuke Kanaji (Research Scientist). Missing: Cunji Gao (Research Scientist)

 

Employment Opportunities
If opportunities are available, they will be listed on the Employment page.

Contact Information
Phone: (414) 937-6237
Fax: (414) 937-6284
E-mail: peter.newman@bcw.edu