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Ph.D. (1991)
Kanpur University
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Sanjeev
Sahni
Assistant Professor of Medicine Hematology-Oncology Unit
Primary Appointment:
Department
of Medicine
GEBS Cluster Affiliations:
Immunology, Microbiology, and Virology - IMV
Contact Information:
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University of Rochester
School of Medicine and Dentistry
601 Elmwood Ave, Box 610 (Room 3-8171)
Rochester, New York 14642
Tel.: (585) 275-0439
Fax: (585) 473-4314
E-Mail: sanjeev_sahni@urmc.rochester.edu
Research:
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Rickettsia-Induced Transcriptional Activation.
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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.
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Joshi SG, Francis CW, Silverman DJ, Sahni SK.
NF-kappaB activation suppresses host cell apoptosis during Rickettsia rickettsii infection via regulatory effects on intracellular localization or levels of apoptogenic and anti-apoptotic proteins.
FEMS Microbiol Lett. 234:333-41, 2004.
Rydkina E, Sahni SK, Santucci LA, Turpin LC, Baggs RB, Silverman DJ.
Selective modulation of antioxidant enzyme activities in host tissues during Rickettsia conorii infection.
Microb Pathog. 36:293-301, 2004.
Sahni A, Guo M, Sahni SK, Francis CW.
Interleukin-1beta but not IL-1alpha binds to fibrinogen and fibrin and has enhanced activity in the bound form.
Blood. 104:409-14, 2004.
Joshi SG, Francis CW, Silverman DJ, Sahni SK.
Nuclear factor kappa B protects against host cell apoptosis during Rickettsia rickettsii infection by inhibiting activation of apical and effector caspases and maintaining mitochondrial integrity.
Infect Immun. 71:4127-36, 2003.
Rydkina E, Sahni A, Silverman DJ, Sahni SK.
Rickettsia rickettsii infection of cultured human endothelial cells induces heme oxygenase 1 expression.
Infect Immun. 70:4045-52, 2002.
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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