UR Faculty: Patricia J. Simpson-Haidaris

Ph.D. (1981) Notre Dame	Patricia J. Simpson-Haidaris Associate Professor of Medicine Hematology-Oncology Unit, of Microbiology & Immunology and of Pathology and Laboratory Medicine Primary Appointment: Department of Medicine GEBS Cluster Affiliations: Cellular and Molecular Basis of Medicine - CMM Immunology, Microbiology, and Virology - IMV Contact Information: University of Rochester School of Medicine and Dentistry 601 Elmwood Ave, Box 610 Rochester, New York 14642 Tel.: (585) 275-8267 Fax: (585) 473-5623 E-Mail: PJ_SimpsonHaidaris@urmc.rochester.edu Research: Role of Fibrinogen in Acute Inflammation.
Research Overview
The research interests of my laboratory are broadly based on the role of fibrinogen in the pathogenesis of inflammatory disease progression and resolution in the lung, the vasculature and in the metastatic potential of breast and prostate cancers. We were the first to demonstrate that breast cancer cells and lung epithelium are sites of extrahepatic fibrinogen gene expression, protein synthesis and secretion. Interestingly, fibrinogen synthesis by lung epithelium appears to require an inflammatory stimulus mediated by interleukin-6, which is enhanced by glucocorticoids. Fibrinogen synthesized by lung epithelium is deposited into the extracellular matrix as conformationally altered fibrinogen, not fibrin, the major plasma protein of coagulation. These results led us to question the role of fibrinogen in maintenance of homeostasis rather than hemostasis. To that end, we identified fibrinogen as a heparin binding protein, which is a well-described feature of extracellular matrix proteins that function in maintenance of cellular integrity and tissue architecture. Additional studies have shown that the heparin binding domain of matrix fibrinogen is important in mediating cellular responses of proliferation and migration. Interestingly, depending on the cell-type (fibroblasts or breast carcinoma cells) and the context of the microenvironment, fibrinogen has opposing effects on cellular responses of migration and proliferation. Together, these data suggest that fibrinogen plays a significant role in cellular responses to inflammation, wounding, and tumorigenesis. Future experiments will address how fibrinogen functions as an extracellular matrix protein in the metastatic potential of breast and prostate carcinoma and in signal transduction pathways of wound repair.
Recent Publications
Wells J, Gigliotti F, Simpson-Haidaris PJ, Haidaris CG. Epitope mapping of a protective monoclonal antibody against Pneumocystis carinii with shared reactivity to Streptococcus pneumoniae surface antigen PspA. Infect Immun. 72:1548-56, 2004. Rybarczyk BJ, Lawrence SO, Simpson-Haidaris PJ. Matrix-fibrinogen enhances wound closure by increasing both cell proliferation and migration. Blood. 102:4035-43, 2003. Duan HO, Simpson-Haidaris PJ. Functional analysis of interleukin 6 response elements (IL-6REs) on the human gamma-fibrinogen promoter: binding of hepatic Stat3 correlates negatively with transactivation potential of type II IL-6REs. J Biol Chem. 278:41270-81, 2003. Pereira M, Rybarczyk BJ, Odrljin TM, Hocking DC, Sottile J, Simpson-Haidaris PJ. The incorporation of fibrinogen into extracellular matrix is dependent on active assembly of a fibronectin matrix. J Cell Sci. 115:609-617, 2002. Meh DA, Mosesson MW, Siebenlist KR, Simpson-Haidaris PJ, Brennan SO, DiOrio P, Thompson K, DiMinno G. Fibrinogen Naples I (Bbeta A68T) nonsubstrate thrombin-binding capacities. Thromb Res. 103:63-73, 2001. Rybarczyk BJ, Simpson-Haidaris PJ. Tumors and Fibrinogen: the role of fibrinogen as an extracellular matrix protein. Ann N Y Acad Sci. 936:406-425, 2001. Pereira M, Simpson-Haidaris PJ. Fibrinogen modulates gene expression in wounded fibroblasts. Ann N Y Acad Sci. 936:438-43, 2001. Odrljin TM, Haidaris CG, Lerner NB, Simpson-Haidaris PJ. Integrin alphavbeta3-mediated endocytosis of immobilized fibrinogen by A549 lung alveolar epithelial cells. Am J Respir Cell Mol Biol 24:12-21, 2001. Michelsen AE, Santi C, Holme R, Lord ST, Simpson-Haidaris PJ, Solum NO, Pedersen TM, Brosstad F. The charge-heterogeneity of human fibrinogen as investigated by 2D electrophoresis. Thromb Res. 100:529-539, 2000. Rybarczyk BJ, Pereira M, Simpson-Haidaris PJ. Characterization of a monoclonal antibody, D73H, that maps to a highly conserved region on fibrinogen Bbeta chain. Thromb Haemost. 84:43-8, 2000. Rybarczyk BJ, Simpson-Haidaris PJ. Fibrinogen assembly, secretion, and deposition into extracellular matrix by MCF-7 human breast carcinoma cells. Cancer Res. 60:2033-9, 2000. Lee LH, Gigliotti F, Wright TW, Simpson-Haidaris PJ, Weinberg GA, Haidaris CG. Molecular characterization of KEX1, a kexin-like protease in mouse Pneumocystis carinii. Gene. 242:141-50, 2000. Shi RJ, Simpson-Haidaris PJ, Marder VJ, Silverman DJ, Sporn LA. Post-transcriptional regulation of endothelial cell plasminogen activator inhibitor-1 expression during R. rickettsii infection. Microb Pathog. 28:127-33, 2000. Nguyen MD, Simpson-Haidaris PJ. Cell type-specific regulation of fibrinogen expression in lung epithelial cells by dexamethasone and interleukin-1beta. Am J Respir Cell Mol Biol. 22:209-17, 2000. Publication list, as provided by PubMed. PubMed is maintained by the National Library of Medicine and provides complete abstracts of all publications, as well as links to the full text of many articles (at journal homepages).

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