Sanjeev K. Sahni, Ph.D.
Associate Professor, Department of Pathology;
Faculty Member, Institute for Human Infections and Immunity
University of Texas Medical Branch
Department of Pathology
5.210 Mary Moody Northen Pavilion
301 University Blvd,
Galveston, TX 77555-0428
Office: (409) 772-3651
Fax: (409) 747-2400
||Field of Study
Lucknow University, Lucknow (U.P.), India
|Zoology, Botany, Chemistry
||Lucknow University, Lucknow (U.P.), India
||Kanpur University, Kanpur (U.P.), India
||National Merit Scholarship from U.P. Government.
||Recognition of Merit from Lucknow Christian Degree College.
||Inclusion in the Merit List for Second position in M.S. Biochemistry at Lucknow University.
||National Merit Research Fellowship Award from University Grants Commission, Government of India.
||National Merit Junior Research Fellowship from Council of Scientific and Industrial Research, Government of India.
||Senior Research Fellowship from Council of Scientific and Industrial Research, Government of India.
||Recognition for prominence and dedication to the chosen field of research at 1st Annual Excellence in Research Day at University of Rochester Medical Center.
||American Society of Rickettsiology Travel Grant Award for research presented at The 20th Meeting of the American Society for Rickettsiology and The 5th International Conference on Bartonella as Emerging Pathogens (Presenting author: Dr. Elena Rydkina).
||American Society for Rickettsiology Travel Grant Award for research presented at The 21st Meeting of the American Society for Rickettsiology.
||American Society of Rickettsiology Travel Grant Award for research presented at The 23rd Meeting of the American Society for Rickettsiology (Presenting author: Punsiri M. Colonne).
||Post-Doctoral Research Associate, Department of Psychiatry, College of Medicine, University of Illinois, Chicago, IL.
||Post-Doctoral Fellow, Department of Biophysics, University of Rochester Medical Center, Rochester, NY.
||Research Assistant (Medicine), Hematology Unit, Department of Medicine, University of Rochester Medical Center, Rochester, NY.
||Research Assistant Professor, Vascular Medicine Unit, Department of Medicine, University of Rochester Medical Center, Rochester, NY.
||Assistant Professor of Medicine (Primary appointment), Hematology-Oncology Unit, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY.
||Assistant Professor of Microbiology and Immunology (Secondary appointment), Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY.
||Member: Immunology, Microbiology, and Virology Cluster, University of Rochester School of Medicine and Dentistry, Rochester, NY.
||Associate Professor of Microbiology and Immunology (Primary appointment), Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY.
||Associate Professor (Primary appointment), Department of Pathology, The University of Texas Medical Branch, Galveston, TX.
||Faculty Member), Institute for Human infections and Immunity, The University of Texas Medical Branch, Galveston, TX.
The obligate intracellular bacteria belonging to Rickettsiaspecies 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:
1. 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-kB), 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-kB 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.
2. 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.
3. 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-kB, 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.
ARTICLES IN PEER-REVIEWED JOURNALS:
- Rydkina, E., Silverman, D.J., and Sahni, S.K.*: Activation of p38 stress-activated protein kinase during R. rickettsii infection of human endothelial cells: role in the induction of chemokine response. Cellular Microbiology7: 1519-1530 (2005). PubMed ID: 16153249.
- Clifton, D.R., Rydkina, E., Huyck, H., Pryhuber, G., Freeman, R. S., Silverman, D.J., and Sahni, S.K.*: 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-kB. International Journal of Medical Microbiology 295: 267-278 (2005). PubMed ID: 16128401.
- Clifton, D.R., Rydkina, E., Freeman, R.S., and Sahni, S.K.: NF-kB activation during Rickettsia rickettsii infection of endothelial cells involves the activation of catalytic IkB kinases IKKa and IKKb and phosphorylation/proteolysis of the inhibitor protein IkBa. Infection and Immunity 73: 155-165 (2005). PubMed ID: 15618150.
- Sahni, A., Sahni, S.K., and Francis, C.W.: Endothelial cell activation by IL-1b in the presence of fibrinogen requires avb3. Arteriosclerosis, Thrombosis, and Vascular Biology 25: 2222-2227 (2005). PubMed ID: 16123330.
- Rydkina, E., Sahni, A., Baggs, R.B., Silverman, D.J, and Sahni, S.K.*: Infection of human endothelial cells with spotted fever group rickettsiae stimulates cyclooxygenase-2 expression and release of prostaglandins. Infection and Immunity 74: 5067-5074 (2006). PubMed ID: 16926398.
- Rydkina, E., Sahni, A., Silverman, D.J, and Sahni, S.K.*: Comparative analysis of host cell signaling mechanisms activated in response to infection with Rickettsia conorii and Rickettsia typhi. Journal of Medical Microbiology 56: 896-906 (2007). PubMed ID: 17577053.
- Sahni, S.K.*: Endothelial cell infection and hemostasis (Review article). Thrombosis Research 119: 531-549 (2007). PubMed ID: 16875715.
- Sahni, A., Simpson-Haidaris, P.J., Sahni, S.K., Vaday, G.G., and Francis, C.W.: Endogenous fibrinogen augments the effect of FGF-2 on prostate and lung cancer cell growth. Journal of Thrombosis and Haemostasis 6: 176-183 (2008). PubMed ID: 17949478.
- Rydkina, E., Turpin, L.C., and Sahni, S.K.*: Activation of p38 MAP kinase module facilitates in vitro host cell invasion by Rickettsia rickettsii. Journal of Medical Microbiology 57: 1172-1175 (2008). PubMed ID: 18719192.
- Sahni, S.K.*, Rydkina, E., and Sahni, A.: The proteasome inhibitor MG132 induces nuclear translocation of erythroid transcription factor Nrf2 and cyclooxygenase-2 expression in human vascular endothelial cells. Thrombosis Research 122: 820-825 (2008). PubMed ID: 18377959.
- Sahni, S.K.*, Rydkina, E., and Silverman, D.J.: ‘Rickettsia’ (Book Chapter). In: "Intracellular Niches of Microbes - A Pathogen's Guide through the Host Cell". Edited by Ulrich E. Schaible and Albert Haas, WILEY-VCH, pp. 469-484 (2009). ISBN: 978-3-527-32207-7.
- Sahni, S.K.* and Rydkina, E.: Host cell interactions with pathogenic Rickettsiaspecies. (Invited Review). Future Microbiology 4: 323-339 (2009). PubMed ID: 19327117.
- Bechelli, J.R., Rydkina, E., Colonne, P.M., and Sahni, S.K.*: Rickettsia rickettsii infection protects human microvascular endothelial cells against staurosporine-induced apoptosis by a cIAP2-independent mechanism. Journal of Infectious Diseases 199: 1389-1398 (2009). PubMed ID: 19358671.
- Sahni, A., Arévalo, M.T., Sahni, S.K., and Simpson-Haidaris, P.J.: The VE-cadherin binding domain of fibrinogen induces endothelial barrier permeability and enhances transendothelial migration of malignant breast epithelial cells. International Journal of Cancer125: 577-584 (2009). PubMed ID: 19358279.
- Sahni, S.K.*: Vascular inflammation during human rickettsioses: an essential host response and a potential target for supplemental therapy. (Invited Review). Anti-inflammatory and Anti-allergy Agents in Medicinal Chemistry 8: 203-213 (2009).
- Rydkina, E., Turpin, L.C., Silverman, D.J., and Sahni, S.K.: Rickettsia rickettsii infection of human pulmonary microvascular endothelial cells: modulation of cyclooxygenase-2 expression. Clinical Microbiology and Infection 15(S2): 300-302 (2009). PubMed ID: 19438652.
- Sahni, S.K.*, Kiriakidi, S., Colonne, P.M., Sahni, A., and Silverman, D.J.: Selective activation of Signal Transducer and Activator of Transcription (STAT) proteins STAT1 and STAT3 in human endothelial cells infected with Rickettsia rickettsii. Clinical Microbiology and Infection15(S2): 303-304 (2009). PubMed ID: 19438651.
- Sahni, S.K.* and Rydkina, E.: Progress in the functional analysis of rickettsial genes through directed mutagenesis of Rickettsia prowazekii phospholipase D. (Priority Paper Evaluation). Future Microbiology 4: 1249-1253 (2009). PubMed ID: 19995185.
- Rydkina, E., Turpin, L.C., and Sahni, S.K.*: Rickettsia rickettsii infection of human macrovascular and microvascular endothelial cells reveals activation of both common and cell type-specific host response mechanisms. Infection and Immunity 78: 2599-2606 (2010). PubMed ID: 20385756.
- Sahni, S.K.*, Rydkina, E., and Simpson-Haidaris, P. J.: Innate Immune Response and Inflammation: Roles in Pathogenesis and Protection. In Rickettsiales (Editors Azad, A. F., and Palmer, G. H., 2011, ASM Press).