 Ph.D.
(1991) |
Sanjeev Sahni
Associate Professor of Microbiology &
Immunology
Primary Appointment: Graduate
Degree Programs |
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| Contact Information | ||
| University of Rochester School of Medicine and Dentistry 601 Elmwood Ave, Box 672 Rochester, New York 14642 |
Phone:
(585) 275-0439 E-Mail: Sanjeev_Sahni@ urmc.rochester.edu |
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- Research Focus
- Host interactions with pathogenic Rickettsia species
- Research Overview
- The obligate intracellular bacteria belonging to Rickettsia
species are etiological agents of the spotted fever and typhus groups (SFG and TG)
of rickettsial diseases in almost all geographic locations worldwide.
Rocky Mountain spotted fever and epidemic typhus, caused respectively
by R. rickettsii and R. prowazekii,
are serious infections that can be fatal in children, elderly, and
immunodeficient or misdiagnosed/untreated patients. A major clinical
hallmark is the infection of endothelial cell lining of vessels, ultimately
leading to vascular damage and associated pathologies. The ongoing research
projects in my laboratory are focused on the following aspects of
rickettsial pathogenesis:
- Rickettsia rickettsii infects and proliferates predominantly within vascular endothelial cells, which respond by activating a series of distinct signal transduction pathways. R. rickettsii infection of endothelial cells results in the activation of nuclear factor-kappaB (NF-ΚB), a transcription factor which controls the expression of an array of genes involved in bacterial infections, immune response, and apoptosis. The anti-apoptotic functions of NF-ΚB are critical for the protection of host cell from apoptotic death during R. rickettsii infection. One of our major goals is to further our understanding of signaling mechanisms underlying Rickettsia-induced transcriptional activation, to evaluate their participation in the host cell response to infection, and to investigate if interfering with these signals affects rickettsial replication.
- Vascular endothelium is a multifunctional endocrine and paracrine organ involved in the modulation of blood flow and vessel tone, coagulation, and regulation of immune and inflammatory responses. In various diseases, harmful effects of reactive oxygen species (ROS) play an important role in endothelial dysfunction. Our goal is to elucidate regulatory mechanisms controlling redox homeostasis, acute inflammation, and vascular permeability in the host vasculature during Rickettsia infection to identify new and unique targets for therapeutic interventions.
- While apoptosis serves as an important host defense mechanism to restrict proliferation and ensuing pathogenesis during bacterial infections, intracellular rickettsiae require intimate association with the target host cells for their growth/spread. It is thus possible that like other intracellular pathogens, rickettsiae may also utilize strategies to inhibit host apoptosis early during the infection for sake of their own survival. Identified and described by our laboratory, one such strategy during endothelial cell infection of R. rickettsii is the activation of NF-ΚB, but nothing is known about cell signaling events during infection with and potential antiapoptotic activities of typhus group organisms. To address this critical gap in the existing knowledge of rickettsial pathogenetic mechanisms is highly significant because of distinctive differences in the intracellular behavior of SFG and TG organisms and the potential for intentional use of R. prowazekii (Class B on CDC list) and R. rickettsii (Category C) as bioterror agents.
- Recent Publications
- Rydkina E, Turpin LC, Sahni SK Activation of p38 mitogen-activated protein kinase module facilitates in vitro host cell invasion by Rickettsia rickettsii.J Med Microbiol. 2008 Sep;57(Pt 9):1172-5
- Sahni SK, Rydkina E, Sahni A. The proteasome inhibitor MG132 induces nuclear translocation of erythroid transcription factor Nrf2 and cyclooxygenase-2 expression in human vascular endothelial cells. Thromb Res. 2008 Mar 28;
- Sahni SK, " Endothelial cell infection and hemostasis" Thromb Res. 2007;119(5):531-49
- Sahni A, Simpson-Haidaris PJ, Sahni SK, Vaday GG, Francis CW "Fibrinogen synthesized by cancer cells augments the proliferative effect of FGF-2." J Thromb Haemost. 2007 Oct 20;
- Rydkina E, Sahni A, Silverman DJ,
Sahni SK. "Comparative
analysis of host-cell signalling mechanisms activated in response to
infection with Rickettsia conorii and Rickettsia typhi." J
Med Microbiol. 2007 Jul;56(Pt 7):896-906.
Rydkina E, Sahni A, Baggs RB, Silverman DJ, Sahni SK. "Infection of human endothelial cells with spotted Fever group rickettsiae stimulates cyclooxygenase 2 expression and release of vasoactive prostaglandins." Infect Immun. 2006 Sep;74(9):5067-74.
Sahni SK. "Endothelial cell infection and hemostasis." Thromb Res. 2007;119(5):531-49. Epub 2006 Jul 26.
Sahni SK, Rydkina E, Sahni A, Joshi SG, Silverman DJ. "Potential roles for regulatory oxygenases in rickettsial pathogenesis." Ann N Y Acad Sci. 2005 Dec;1063:207-14.
Rydkina E, Silverman DJ, Sahni SK. "Similarities and differences in host cell signaling following infection with different Rickettsia species." Ann N Y Acad Sci. 2005 Dec;1063:203-6. Review.
Rydkina E, Silverman DJ, Sahni SK. "Activation of p38 stress-activated protein kinase during Rickettsia rickettsii infection of human endothelial cells: role in the induction of chemokine response." Cell Microbiol. 2005 Oct;7(10):1519-30.
Clifton DR, Rydkina E, Huyck H, Pryhuber G, Freeman RS, Silverman DJ, Sahni SK. "Expression and secretion of chemotactic cytokines IL-8 and MCP-1 by human endothelial cells after Rickettsia rickettsii infection: regulation by nuclear transcription factor NF-kappaB." Int J Med Microbiol. 2005 Aug;295(4):267-78.
Sahni A, Sahni SK, Francis CW. "Endothelial cell activation by IL-1beta in the presence of fibrinogen requires alphavbeta3." Arterioscler Thromb Vasc Biol. 2005 Oct;25(10):2222-7. Epub 2005 Aug 25.
Clifton DR, Rydkina E, Freeman RS, Sahni SK. "NF-kappaB activation during Rickettsia rickettsii infection of endothelial cells involves the activation of catalytic IkappaB kinases IKKalpha and IKKbeta and phosphorylation-proteolysis of the inhibitor protein IkappaBalpha." Infect Immun. 2005 Jan;73(1):155-65.
Guo M, Sahni SK, Sahni A, Francis CW. "Fibrinogen regulates the expression of inflammatory chemokines through NF-kappaB activation of endothelial cells." Thromb Haemost. 2004 Oct;92(4):858-66.
Sahni A, Sahni SK, Simpson-Haidaris PJ, Francis CW. "Fibrinogen binding potentiates FGF-2 but not VEGF induced expression of u-PA, u-PAR, and PAI-1 in endothelial cells." J Thromb Haemost. 2004 Sep;2(9):1629-36.