Research Assistant Professor

ACADEMIC QUALIFICATIONS

Ph.D., Pathobiology (2006). Kansas State University, Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine. Dissertation title: Characterization of severe acute respiratory syndrome (SARS) nucleocapsid protein. Under the direction of Dr. Raymond Rowland.

M.Sc., Biochemistry (2000). T. N. Medical College, Mumbai University, Mumbai, India. Thesis title: Analysis of epinephrine and nor-epinephrine levels in patients suffering from Schizophrenia and hypertensive stress. Under the direction of Dr. Vinay Phatake.

B.Sc., Chemistry and Biochemistry (1998). Mithibhai College, Mumbai University, Mumbai, India.

HONORS, AWARDS AND MEMBERSHIPS

2006-2008: Postdoctoral fellow. Department of Biology, University of North Carolina at Charlotte

December 2005: The Don Kahn Award for outstanding overall presentation at “ The Conference for Research Workers in Animal Diseases (CRWAD)”, St Louis, MO.,

2005: Graduate student travel grant to attend CRWAD from KSU-Graduate Student Association. 2005.

2005: Excellence in Research, first place, Phi-Zeta Research Forum, College of Veterinary Medicine and Pathobiology, Kansas State University, Manhattan, KS. 2005.

2006- present : American Association of Immunologists, Student/Fellow member.

2008- present: Society of Neuroscience.

CURRENT RESEARCH PROJECTS

The role of the neuropeptide substance P in microbially induced CNS inflammation

While glial cells are recognized for their roles in maintaining neuronal function, there is growing appreciation of the ability of resident central nervous system (CNS) cells such as microglia and astrocytes to initiate and/or augment inflammation following trauma or infection. The neuropeptide, substance P (SP), is well known to augment inflammatory responses at peripheral sites and its presence throughout the CNS raises the possibility that this tachykinin might serve a similar function within the brain. In support of this hypothesis, our groups has recently demonstrated the expression of high affinity receptors for SP (NK-1 receptors) on resident CNS cells and shown that this neuropeptide can significantly elevate inflammatory prostanoid production by these cells following bacterial challenge. Using clinically relevant bacterial pathogens like Neisseria Meningitidis, the causative agent of meningitis and Borrelia burgdorferi, the causative agent of lyme disease and lyme neuroborreliosis, we are working to develope animals models to study bacterial infections of the CNS. Recently, we have demonstrated that endogenous SP/NK-1 receptor interactions are an essential component in the initiation and/or progression of CNS inflammation in vivo following intracerebral administration of clinically relevant microbial CNS pathogens. Microbially induced elevations in the production of the inflammatory cytokines, IL-6 and TNF-alpha, and decreases in the production of the immunosuppressive cytokine, IL-10, are markedly attenuated in mice genetically deficient in the expression of the NK-1 receptor. Similarly, increased expression of IL-6 and TNF-alpha, and decreases in IL-10, are almost totally abolished in infected wild type animals that received s.c. administration of a specific NK-1 receptor antagonist, L703,606 in vivo. Furthermore, we demonstrate that pathogen associated demyelination and astrogliosis are also markedly reduced in the absence of endogenous SP/NK-1 receptor interactions. Using isolated cultures of microglia and astrocytes we have shown that SP can augment inflammatory cytokine production by these glial cell types following exposure to CNS pathogens and that this effect is mediated by ligation of the NK-1 receptor. Together, this research provides compelling evidence of a role for SP in microglia and astrocyte responses to clinically relevant bacterial pathogens and may represent a novel therapeutic target to combat potentially lethal CNS inflammation.

The role of Rig-I like receptors (RLR) in the reognition of viral pathogens in the CNS and the initiation of immune response.

The order Mononegavirales includes numerous viral etiological agents of fatal human diseases with central nervous system (CNS) involvement, most notably rabies virus. Like rabies virus, vesicular stomatitis virus (VSV) is a negative-sense single-stranded RNA virus belonging to the Rhabdoviridae family, and closely resembles its deadly cousin. VSV is neurotropic in mice and has been shown to elicit rapid and severe encephalitis with a high degree of mortality following intranasal inoculation and is therefore used as a mouse model for rabies infection. Interestingly, VSV-induced encephalitis appears to be T-cell independent, having been observed in athymic mice after viral administration. Therefore, it is likely that the innate immune functions of resident CNS cells play an important role in the rapid inflammatory response following VSV infection. There is a growing appreciation that resident CNS cells such as microglia and astrocytes can initiate and augment inflammation following trauma or infection. These important glial cells are ideally situated to detect traumatic injury or the presence of pathogens and microglia can respond by migrating to the site of injury where they proliferate. They become activated at the site of challenge and assume many of the immune effector functions typically associated with macrophages and dendritic cells, including the production of key pro-inflammatory molecules such as TNF-a and IL-6 . The ability of microglia and astrocytes to respond to VSV has previously been demonstrated, but the mechanisms underlying glial cell activation following infection with this viral pathogen have not been defined. The current project involves studying the mode of recognition of viral pathogens by resident CNS cells and the initiation of protective, but sometimes harmful immune response in the brain.

Microglia and astrocytes possess cell surface Toll-like receptors (TLRs) including TLR3, TLR7, TLR8, and TLR9 that can perceive viral motifs present in the extracellular milieu or that have been internalized. Recently, a newly described group of molecules have been shown to function as intracellular sensors for replicative viral RNA. The retinoic acid-inducible gene I (RIG-I)-like helicases, RIG-I and melanoma differentiation-associated antigen 5 (MDA5), are soluble proteins found in the cytosol of many cell types and have been shown to mediate innate immune responses to viral RNA. Interestingly, accumulating evidence suggests that these molecules can discriminate between different virus types despite utilizing similar signaling pathways. Genomic RNA from several Mononegaviruses, including VSV and the paramyxovirus, Sendai virus (SeV), has been demonstrated to specifically activate immune responses via RIG-I. In contrast, picornaviruses, which are positive-sense RNA viruses, and synthetic poly(I:C) molecules appear to initiate MDA5-mediated effects. To date, the expression of these novel pattern recognition receptors has not been investigated in murine microglia and astrocytes.

We have recently demonstrated that primary murine glial cells constitutively express RIG-I and MDA5 as well as their essential downstream effector molecules. Furthermore, the expression of these molecules is significantly upregulated following exposure to VSV or SeV. Infection of cells with Rig-1 putative ligand phosphorylated RNA results in secretion of inflammatory cytokines. As such, the presence of these intracellular sensors for replicative viral motifs may reflect an important role for such molecules in the immune response of microglia and astrocytes following CNS infection.

PUBLICATIONS

Research Papers

1. Rowland, R.R, Chauhan, V., Fang, Y, Pekosz, A, Kerrigan, M, and Burton, M.D. 2005. Intracellular localization of the severe acute respiratory syndrome corona virus nucleocapsid protein: absence of nucleolar accumulation during infection and after expression as a recombinant protein in Vero cells. J. Virol. 79: 11507-11512.
2. Chauhan, V.S., Sterka, D.G. Jr., Gray, D.L., Bost, K.L., and Marriott, I. 2008. Neurogenic exacerbation of microglial and astrocyte responses to Neisseria meningitidis and Borrelia burgdorferi. J. Immunol. 180 :8241-9.
3. Chauhan V.S., Sterka, D.G. Jr., Furr, S.R., and Marriott, I. 2008. Inflammatory role of NOD2 in glial responses to bacterial CNS infections. Glia. Sept 19 2008.
4. Furr, S.R., Chauhan, V.S., Sterka, D.G., Grdzelishvili, V., and I. Marriott. 2008. Characterization of retinoic acid-inducible gene-1 expression in primary murine glia following exposure to vesicular stomatitis virus. J. Neurovirol. In Press.
5. Sahraei M., Chauhan, V.S., and I. Marriott. The role of NOD2 in osteoblast inflammatory responses to bacterial infection. Manuscript submitted.
6. Sterka, D.G., Chauhan, V.S., Grdzelishvili, V., and I. Marriott. 2008. Vesicular stomatitid virus and Sendai virus infect and induce immune responses in murine resident glial cells. Manuscript in preparation.

Peer-evaluated Reviews

1. Chauhan, V.S., and Marriott, I. 2007. Bacterial infections of the central nervous system: a critical role for resident glial cells in the initiation and progression of inflammation. Curr. Immunol. Rev. 3: 133-143.
2. Chauhan, V.S., and Marriott, I. Role of substance P signaling in pathogen associated neurodegenerative disorders. Review in preparation

Communications

1. Chauhan, V.S., Sterka, D. Jr., and Marriott, I. (2007). Substance P augments bacterially induced inflammatory cytokine production by resident CNS cells. J. Immunol. 178: 40.9.
2. Chauhan, V. S., and Marriott. I. Exacerbation of inflammatory glial responses to bacterial pathogens by the neuropeptide substance P, Abstracts of Annual Neuroscience Meeting. Submitted.

Scientific Presentations

1. Chauhan, V.S. and I. Marriott. 2008. “Exacerbation of inflammatory glial responses to CNS pathogens by the neuropeptide substance P.” Poster presentation. Neuroscience, Washington D.C.
2. Chauhan V, D. Sterka and I. Marriott. 2007. “Substance P augments bacterially induced inflammatory cytokine production by resident CNS cells.” Poster presentation. AAI, Miami Beach, FL.
3. Chauhan V, J. Patton, J. M. Rowland and R. R. Rowland. 2006. An aspartic acid residue at position 372 is involved in the cytoplasmic retention of the SARS-coronavirus nucleocapsid protein. Poster presentation. COBRE-CSF, Lawrence, KS.
4. Chauhan, V., J. M. Rowland and R. R. Rowland. 2005. Absence of nuclear targeting activity within the lysine-rich domain of the SARS-CoV N protein is the result of an aspartic acid residue at position 372. Oral Presentation. The Conference for Research Workers in Animal Diseases, St. Louis, MO.
5. Chauhan, V. and R. R. Rowland. 2005. Does SARS-CoV N traffic to the nucleolus? Oral presentation. The American Society of Microbiology, Manhattan, KS.
6. Chauhan, V. and R. R. Rowland. 2005. Unique localization properties of SARS-CoV N protein. Oral presentation. Phi-Zeta research forum, KSU-CVM, Manhattan, KS.
7. Rowland R. R., V. Chauhan, Y. Fang and A. Pekosz. 2005. Does SARS-CoV N traffic to the nucleolus? Poster presentation. Xth International Nidovirus Symposium : toward control of SARS and other Nidovirus disease. Colorado Springs, CO.
8. Chauhan, V. and R. R. Rowland. 2004. Characterization of SARS-CoV N protein. Poster presentation. COBRE meeting, Lawrence, KS.
9. Delandre C., V. Chauhan and S. Todd. 2004. The Tetraspanin CD9 is involved in EGFR- mediated Cell Motility via HB-EGF. Poster presentation. The Tetraspanin conference, Pine Mountain, GA.
10. Delandre C., V. S. Chauhan, and S. Todd. 2004. Regulation of EGFR by the tetraspanin CD9. Oral presenatation. The 30th Annual Student Research Forum, Division of Biology, Kansas State University, Manhattan, KS.