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Robert W. Colman, MD

Professor Emeritus, Medicine

Professor, Physiology

Professor, Microbiology and Immunology

Professor, Fels Institute for Cancer Research and Molecular Biology

Telephone:  215-707-4665

Fax:  215-707-4855

Email: colmanr@temple.edu

Sol Sherry Thrombosis Research Center

Department of Physiology

Department of Microbiology and Immunology

Fels Institute for Cancer Research and Molecular Biology

M.A., Harvard University, Cambridge, MA, 1956 (summa cum laude)

 

MD, Harvard Medical School, Cambridge, MA, 1960 (cum laude)

 

Internship, Boston City Hospital (Harvard Medical Service), 1961

 

Clinical Fellow in Hematology, Washington University School of Medicine (Carl Moore), St. Louis, MO, 1966

 

Research Fellow, Washington University School of Medicine, St. Louis, MO (Sol Sherry), 1967

 

Clinical Associate, National Heart Institute, National Institutes of Health, Bethesda, MD, 1962-1964

 

Assistant Resident in Medicine, Washington University School of Medicine, St. Louis, MO, 1965

 

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• American Board of Internal Medicine, 1968
• Diplomate in the Subspecialty of Hematology, 1974

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• Association of American Physicians
• American Society for Clinical Investigation
• American Society of Biological Chemists
• International Society on Thrombosis and Haemostasis
• American Physiological Society
• American Society for Investigative Pathology
• Executive Committee, Council of Thrombosis of American Heart Association
• American Federation for Clinical Research
• Fellow of the American College of Physicians
• American Society of Hematology
  International Society of Hematology, Subcommittee on Hemostasis
• American Society of Hematology Member, Microcirculatory Thrombosis Task Group
• NHLBI, Chairman, Subcommittee on Contact Factor
• International Committee on Haemostasis and Thrombosis Board of Governors
• American Heart Association, Southeastern Pennsylvania Chapter
• Member, Nominations Committee for Contributions to Haemostasis
• American Society of Hematology, Subcommittee on Hemostasis
• Accreditation Council for Graduate Education in Hematology
  Peripatetic Club
• Interurban Clinical Club, Senior Advisory Committee

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Thrombosis and hemostasis

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My research activities center around two separate, but interrelated, areas: (1) The role of high molecular weight kininogen thrombosis, monocyte secretion, neutrophil stimulation, inflammation and angiogenesis, both in purified systems and in human disease states such as inflammatory bowel disease and arthritis and (2) Stimulus-response coupling in platelets as mediated by cAMP phosphodiesterase type 3A [PDE3A].

Monoclonal peptides, antibodies, molecular biological techniques and molecular modeling are also being used to probe structure-function relationships in kininogen. The peptide sequences responsible for the ability of cleaved kininigen and domain 5 to inhibit angiogenesis and stimulate monocytes to secrete cytokines and chemokines is currently being investigated both in vitro and in vivo using recombinant proteins, site-directed mutagenesis, domain deletion and designed peptides. The structural requirements for kininogen and domain 3 to inhibit thrombosis are being delineated in a model of arterial endothelial injury in an inbred Lewis rat. .The effect of treating angiogenesis with a monoclonal antibody to kininogen in experimental inflammatory bowel disease and arthritis in the same rat is being evaluated.The same antibody is being used to treat tumor angiogenesis in mice.

We have purified platelet cAMP phosphodiesterase type 3A and can be labeled in the active site with a cAMP affinity reagent. We are now investigating the amino acids which are covalently labeled. To place these modified amino acids in the primary structure, we have proteolyzed and sequenced the covalently modified the enzyme and performed site-directed mutagenesis to further define its active site. A new cGMP affinity reagent will be used to probe the active and regulatory sites. We have shown that Akt [PKB] phosphorylated and activated PDE3A.Since Akt is activated by thrombin, we will further investigate thrombin-induced platelet aggregation in PDE3A and Akt gene knockouts.

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Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

20103219. Colman R, Invited commentary. Ann Thorac Surg 89:1(123-4)2010 Jan

19966052. Khan MM, Liu Y, Khan ME, Gilman ML, Khan ST, Bromberg M, Colman RW, Upregulation of tissue factor in monocytes by cleaved high molecular weight kininogen is dependent on TNF-alpha and IL-1beta. Am J Physiol Heart Circ Physiol 298:2(H652-8)2010 Feb

19874467. Wu Y, Dai J, Schmuckler NG, Bakdash N, Yoder MC, Overall CM, Colman RW, Cleaved high molecular weight kininogen inhibits tube formation of endothelial progenitor cells via suppression of matrix metalloproteinase 2. J Thromb Haemost :()2009 Oct 23

19483730. Liu Y, Pixley R, Fusaro M, Godoy G, Kim E, Bromberg ME, Colman RW, Cleaved high-molecular-weight kininogen and its domain 5 inhibit migration and invasion of human prostate cancer cells through the epidermal growth factor receptor pathway. Oncogene 28:30(2756-65)2009 Jul 30

18495808. Liu Y, Cao DJ, Sainz IM, Guo YL, Colman RW, The inhibitory effect of HKa in endothelial cell tube formation is mediated by disrupting the uPA-uPAR complex and inhibiting its signaling and internalization. Am J Physiol Cell Physiol 295:1(C257-67)2008 Jul

18394675. Hung SH, Liu AH, Pixley RA, Francis P, Williams LD, Matsko CM, Barnes KD, Sivendran S, Colman RF, Colman RW, A new nonhydrolyzable reactive cGMP analogue, (Rp)-guanosine-3',5'-cyclic-S-(4-bromo-2,3-dioxobutyl)monophosphorothioate, which targets the cGMP binding site of human platelet PDE3A. Bioorg Chem 36:3(141-7)2008 Jun

18222260. Colman R, Invited commentary. Ann Thorac Surg 85:2(542)2008 Feb

18062965. Liu Y, Sainz IM, Wu Y, Pixley R, Espinola RG, Hassan S, Khan MM, Colman RW, The inhibition of tube formation in a collagen-fibrinogen, three-dimensional gel by cleaved kininogen (HKa) and HK domain 5 (D5) is dependent on Src family kinases. Exp Cell Res 314:4(774-88)2008 Feb 15

17597995. Sainz IM, Pixley RA, Colman RW, Fifty years of research on the plasma kallikrein-kinin system: from protein structure and function to cell biology and in-vivo pathophysiology. Thromb Haemost 98:1(77-83)2007 Jul

17585065. Wu Y, Rizzo V, Liu Y, Sainz IM, Schmuckler NG, Colman RW, Kininostatin associates with membrane rafts and inhibits alpha(v)beta3 integrin activation in human umbilical vein endothelial cells. Arterioscler Thromb Vasc Biol 27:9(1968-75)2007 Sep

17392505. Zhang W, Colman RW, Thrombin regulates intracellular cyclic AMP concentration in human platelets through phosphorylation/activation of phosphodiesterase 3A. Blood 110:5(1475-82)2007 Sep 1

17155949. Bior AD, Pixley RA, Colman RW, Domain 5 of kininogen inhibits proliferation of human colon cancer cell line (HCT-116) by interfering with G1/S in the cell cycle. J Thromb Haemost 5:2(403-11)2007 Feb

16902163. Khan MM, Bradford HN, Isordia-Salas I, Liu Y, Wu Y, Espinola RG, Ghebrehiwet B, Colman RW, High-molecular-weight kininogen fragments stimulate the secretion of cytokines and chemokines through uPAR, Mac-1, and gC1qR in monocytes. Arterioscler Thromb Vasc Biol 26:10(2260-6)2006 Oct

16873361. Hung SH, Zhang W, Pixley RA, Jameson BA, Huang YC, Colman RF, Colman RW, New insights from the structure-function analysis of the catalytic region of human platelet phosphodiesterase 3A: a role for the unique 44-amino acid insert. J Biol Chem 281:39(29236-44)2006 Sep 29

16842160. Colman RW, Regulation of angiogenesis by the kallikrein-kinin system. Curr Pharm Des 12:21(2599-607)2006

16708906. Isordia-Salas I, Sainz IM, Pixley RA, Martínez-Murillo C, Colman RW, [High molecular weight kininogen in inflammation and angiogenesis: a review of its properties and therapeutic applications] Rev Invest Clin 57:6(802-13)2005 Nov-Dec

16533890. Colman RW, Are hemostasis and thrombosis two sides of the same coin? J Exp Med 203:3(493-5)2006 Mar 20

16268479. Katkade V, Soyombo AA, Isordia-Salas I, Bradford HN, Gaughan JP, Colman RW, Panetti TS, Domain 5 of cleaved high molecular weight kininogen inhibits endothelial cell migration through Akt. Thromb Haemost 94:3(606-14)2005 Sep

16187087. Sainz IM, Isordia-Salas I, Espinola RG, Long WK, Pixley RA, Colman RW, Multiple myeloma in a murine syngeneic model:modulation of growth and angiogenesis by a monoclonal antibody to kininogen. Cancer Immunol Immunother 55:7(797-807)2006 Jul

16059911. Sainz IM, Isordia-Salas I, Castaneda JL, Agelan A, Liu B, DeLa Cadena RA, Pixley RA, Adam A, Sartor RB, Colman RW, Modulation of inflammation by kininogen deficiency in a rat model of inflammatory arthritis. Arthritis Rheum 52:8(2549-52)2005 Aug

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