 Ph.D.
(1991) |
Sanjeev Sahni
Associate Professor of Microbiology &
Immunology
Primary Appointment: Graduate
Degree Programs |
|
| 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 |
|
- Research Focus
- Rickettsia-Induced Transcriptional Activation.
- Research Overview
- Rickettsia
rickettsii is an obligate intracellular bacterium and the
etiologic agent of Rocky Mountain spotted fever; it is also a NIAID
Category C Priority Pathogen, and considered part of the NIAID
Biodefense research effort.
R. 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-kappaB), 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-kappaB are critical for the protection of host cells from apoptotic
death during R.
rickettsii infection. The goal of our research 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.
One set of experiments aims to characterize the activation of IkappaB kinase complex (IKK) and phosphorylation/degradation of IkappaB proteins during infection. The effects of selected, specific inhibitors of IKK and NF-kappaB on replication of Rickettsia organisms will also be studied.
Related studies focus on the activation of mitogen activated protein (MAP) kinases and their involvement in rickettsial invasion of endothelial cells and activation of NF-kappaB. Modulation of MAP kinase cascades will be examined by western blotting and immunostaining , as well as by functional assays.
Finally, we are also examining the regulation of chemokine induction in response to infection and exploring its dependence on the MAP kinase and NF-kappaB pathways. Using different species/strains of Rickettsia with varying pathogenicity, we will investigate the correlation between infection, activation of IKK/NF-kappaB and MAP kinases, and induction of chemokine response. These studies will offer important perspectives in our understanding of rickettsial pathogenesis and may lead to the identification of novel chemotherapy targets. - Recent Publications
- 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.