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Scientific Overview Research Interest Summary Principal Investigators    Yuri Bushkin, Ph.D.
   Theresa Chang, Ph.D.
   Neeraj Chauhan, Ph.D.
   Véronique Dartois, Ph.D.
   Karl Drlica, Ph.D.
   David Dubnau, Ph.D.
   Eliseo A. Eugenin, Ph.D.
   Marila Gennaro, M.D.
   Gilla Kaplan, Ph.D.
   Fred Kramer, Ph.D.
   Barry Kreiswirth, Ph.D.
   Min Lu, Ph.D.
   Leonard Mindich, Ph.D.
   Arkady Mustaev, Ph.D.
   Jyothi Nagajyothi, Ph.D.
   David Perlin, Ph.D.
   Richard Pine, Ph.D.
   Abraham Pinter, Ph.D.
   Marcela Rodriguez, Ph.D.
   Selvakumar Subbian, Ph.D.
   Sanjay Tyagi, Ph.D.
   Christopher Vinnard, M.D.
   Chaoyang Xue, Ph.D.
   Xilin Zhao, Ph.D.

   Research Faculty
   Liang Chen, Ph.D.
   Eugenie Dubnau, Ph.D.
   Jeanette Hahn, Ph.D.
   Salvatore Marras, Ph.D.
   Lanbo Shi, Ph.D.
   Yanan Zhao, Ph.D.

Emeritus Faculty Recent Publications
 
Neeraj Chauhan, Ph.D.

Research Interests  |  Selected Publications   |  Education
 

Public Health Research Institute Center
New Jersey Medical School - Rutgers, The State University of New Jersey
225 Warren Street
Newark, New Jersey 07103

Phone: (973) 854-3470
Fax: (973) 854-3101
e-mail: chauhan1@njms.rutgers.edu


Research Interests

The focus of my current research is the opportunistic human pathogenic yeast, Candida albicans. It is the leading cause of invasive fungal disease in premature infants, surgical patients and cancer patients receiving immunosuppressive chemotherapy. Almost 80% of all AIDS patients suffer from Candidiasis. While candidiasis occurs in the compromised host, on the other hand, vulvovaginal candidiasis (VVC) is more often seen in healthy women, at least for the first episode of the disease. One of the most intriguing aspects of C. albicans is the jump from commensalism to pathogenicity. My research is directed to elucidate the complex signaling pathways that contribute to the virulence & pathogenesis of this organism. Our approaches include molecular, biochemical and immunological techniques to study these events. This involves isolation of encoding genes, construction of knock-out strains to study gene function, DNA Microarrays, and GFP localization etc. Two component signaling proteins (histidine kinases and response regulators) and downstream MAP kinases are the main focus of research. Current effort is focused on:

1. Mechanism of resistance / sensitivity to triazole antifungal drugs:

Two component signal transduction proteins have been reported in bacteria, lower eukaryotes but to date two-component proteins have not yet been identified in animals and are absent in human genome. Previous studies have confirmed the role of two-component proteins in the pathogenesis of C. albicans in a mouse model of hematogenously disseminated candidiasis, survival in human PMNs in vitro, adherence to human esophageal tissue and adaptation to oxidants. These features of two-component proteins make them very attractive target for antifungal drug discovery. We have recently reported that mutants of C. albicans lacking Ssk1p and Chk1p are hypersensitive to triazoles, fluconazole and voriconazole. Importantly, the ssk1 mutant retains the wild type levels of sensitivity to other antifungals such as miconazole, ketoconazole (imidazole), amphotericin B, caspofungin, 5-FC, and a variety of other inhibitors such as Congo red, calcofluor white, and nikkomycin Z. So the hypersensitivity of the ssk1 mutant to triazoles appears to be very specific. The ssk1 mutant has elevated accumulation of fluconazole that may explain its hypersensitivity. Of interest, compared to wild type, both mutants are more readily killed by fluconazole and voriconazole which are normally fungistatic towards this pathogen. Therefore, these mutations result in a fungicidal rather than fungistatic effect with triazoles. An undesirable trait of triazole therapy in general is that resistance can develop, especially in the case of non-albicans Candida species. We hypothesize therefore, that compounds which target Ssk1p or Chk1p may be useful in co-therapy with triazoles to potentiate the activity of the latter compounds. Equally important, my studies will provide new observations on the uptake of triazoles, of which there is very little information in the literature. I also hypothesize that therapy which includes a triazole and a drug which targets Ssk1p or proteins it regulates may enable triazoles to be fungicidal rather than fungistatic. Collectively, our results identify the Ssk1 protein as a promising target for therapeutic strategies. This research is supported by a grant from NIH-NIAID.

2. Host-Pathogen Interactions: Candida adherence and penetration of vascular endothelium / oral epithelium and identification of signal transduction pathway(s) that contribute to Candida albicans invasion.

The incidence of bloodstream infections caused by Candida species has increased dramatically; these organisms now account for 8% of all bloodstream isolates. The mortality associated with candidemia is approx. 40%. Because of this unacceptably high mortality, new strategies to treat and prevent this infection are necessary. Our hypothesis is that the ability of C. albicans to invade and damage host cells is critical for the organism to establish and maintain a deep-seated infection. This hypothesis is based on our finding that C. albicans two-component response regulator ssk1 mutant with decreased virulence in the mouse model of invasive candidiasis and also have reduced adherence to human esophageal tissue and endothelial cells in vitro. We therefore, hypothesize that information relevant to the in vitro interaction of C. albicans and endothelial cells will serve as a model for studying host-Candida interactions. In addition to providing information on adherence, invasion and damage to the vascular endothelium, we also will establish fungal signaling events and protein cross-talk information during pathogenesis. Our hypothesis is that each of these events is crucial to disease development in the vasculature. We are currently using proteomics and DNA microarrays to identify the genes regulated by SSK1 upon interaction with endothelial cells, and the proteins with which it interacts. From the microarray experiments candidate genes will be chosen for construction of knock out stains; mutants will be evaluated phenotypically both in vivo (virulence) and in vitro (with the endothelial cells). The results of these studies will provide the foundation for the future development of novel therapeutic approaches to block candidal adherence and enhance host defense. This research is supported by a grant from American Heart Association (AHA).




Recent Articles

Chauhan N (2015) Two-Component Phosphorelays in Fungal Mitochondria and Beyond. Mitochondrion. in press

Shor E, Chauhan N (2015) A case for two-component signaling systems as antifungal drug targets. PLoS Pathog 11: e1004632. PMI: 25723524

Shah AH, Singh A, Dhamgaye S, Chauhan N, Vandeputte P, Suneetha KJ, Kaur R, Mukherjee PK, Chandra J, Ghannoum MA, Sanglard D, Goswami SK, Prasad R (2014) Novel Role of a Family of Major Facilitator Transporters in Biofilm Development and Virulence of Candida albicans. Biochem J. PMI: 24621232

Mavrianos JD, C. Chauhan, N. (2014) Two-component histidine phosphotransfer protein Ypd1 is not essential for viability in Candida albicans. Eukaryot Cell. In press.

Mavrianos J, Berkow EL, Desai C, Pandey A, Batish M, Rabadi MJ, Barker KS, Pain D, Rogers PD, Eugenin EA, Chauhan N (2013) Mitochondrial two-component signaling systems in Candida albicans. Eukaryot Cell 12: 913-922. PMI: 23584995

Maurya IK, Thota CK, Verma SD, Sharma J, Rawal MK, Ravikumar B, Sen S, Chauhan N, Lynn AM, Chauhan VS, Prasad R (2013) Rationally designed transmembrane peptide mimics of the multidrug transporter protein Cdr1 act as antagonists to selectively block drug efflux and chemosensitize azole-resistant clinical isolates of Candida albicans. J Biol Chem 288: 16775-16787. PMI: 23592791

de Groot PW, Bader O, de Boer AD, Weig M, Chauhan N (2013) Adhesins in human fungal pathogens: glue with plenty of stick. Eukaryot Cell 12: 470-481. PMI: 23397570

Desai C, Mavrianos J, Chauhan N (2011) Candida glabrata Pwp7p and Aed1p are required for adherence to human endothelial cells. FEMS Yeast Res 11: 595-601. PMI: 21726406

Desai C, Mavrianos J, Chauhan N (2011) Candida albicans SRR1, a putative two-component response regulator gene, is required for stress adaptation, morphogenesis, and virulence. Eukaryot Cell 10: 1370-1374. PMI: 21841121

Chauhan N, Kruppa MD (2009) Standard growth media and common techniques for use with Candida albicans. Methods Mol Biol 499: 197-201. PMI: 19152050

Chauhan N (2009) Preparation of samples for proteomic analysis of the Candida albicans cell wall. Methods Mol Biol 499: 149-155. PMI: 19152046

Bambach A, Fernandes MP, Ghosh A, Kruppa M, Alex D, Li D, Fonzi WA, Chauhan N, Sun N, Agrellos OA, Vercesi AE, Rolfes RJ, Calderone R (2009) Goa1p of Candida albicans localizes to the mitochondria during stress and is required for mitochondrial function and virulence. Eukaryot Cell 8: 1706-1720. PMI: 19717740

Menon V, De Bernardis F, Calderone R, Chauhan N (2008) Transcriptional profiling of the Candida albicans Ssk1p receiver domain point mutants and their virulence. FEMS Yeast Res 8: 756-763. PMI: 18616606

Chauhan N, Calderone R (2008) In San-Blas G and Calderone R (eds.), Pathogenic Fungi: Insights in Molecular Biology. Horizon Scientific Press, UK, pp. 171-194.

Chauhan N, Calderone R (2008) Two-component signal transduction proteins as potential drug targets in medically important fungi. Infect Immun 76: 4795-4803. PMI: 18765727

Chauhan N, Kruppa M, Calderone R (2007) The Ssk1p response regulator and Chk1p histidine kinase mutants of Candida albicans are hypersensitive to fluconazole and voriconazole. Antimicrob Agents Chemother 51: 3747-3751. PMI: 17664325

Chauhan N, Calderone R (2007) Virulence factors as drug targets: how and why. The 6th ISHAM Virtual Mycological Congress. Theme: “Antifungal Antibiotics. Oct 16th –Oct 31st 2007 PMI: 0

Sandovsky-Losica H, Chauhan N, Calderone R, Segal E (2006) Gene transcription studies of Candida albicans following infection of HEp2 epithelial cells. Med Mycol 44: 329-334. PMI: 16772226

Menon V, Li D, Chauhan N, Rajnarayanan R, Dubrovska A, West AH, Calderone R (2006) Functional studies of the Ssk1p response regulator protein of Candida albicans as determined by phenotypic analysis of receiver domain point mutants. Mol Microbiol 62: 997-1013. PMI: 17038117

Chauhan N, Latge JP, Calderone R (2006) Signalling and oxidant adaptation in Candida albicans and Aspergillus fumigatus. Nat Rev Microbiol 4: 435-444. PMI: 16710324

Chauhan N, Kumar R, Badhai J, Preet A, Yadava PK (2005) Immunogenicity of cholera toxin B epitope inserted in Salmonella flagellin expressed on bacteria and administered as DNA vaccine. Mol Cell Biochem 276: 1-6. PMI: 16132678

Chauhan N, Ciudad T, Rodriguez-Alejandre A, Larriba G, Calderone R, Andaluz E (2005) Virulence and karyotype analyses of rad52 mutants of Candida albicans: regeneration of a truncated chromosome of a reintegrant strain (rad52/RAD52) in the host. Infect Immun 73: 8069-8078. PMI: 16299301

Singh P, Chauhan N, Ghosh A, Dixon F, Calderone R (2004) SKN7 of Candida albicans: mutant construction and phenotype analysis. Infect Immun 72: 2390-2394. PMI: 15039366

Li D, Gurkovska V, Sheridan M, Calderone R, Chauhan N (2004) Studies on the regulation of the two-component histidine kinase gene CHK1 in Candida albicans using the heterologous lacZ reporter gene. Microbiology 150: 3305-3313. PMI: 15470110

Kruppa M, Krom BP, Chauhan N, Bambach AV, Cihlar RL, Calderone RA (2004) The two-component signal transduction protein Chk1p regulates quorum sensing in Candida albicans. Eukaryot Cell 3: 1062-1065. PMI: 15302838

Chauhan N, Calderone R (2004) In San-Blas G and Calderone R (eds.), Pathogenic Fungi: Cellular and Molecular Biology. Horizon Scientific Press, UK.

Kruppa M, Goins T, Cutler JE, Lowman D, Williams D, Chauhan N, Menon V, Singh P, Li D, Calderone R (2003) The role of the Candida albicans histidine kinase [CHK1) gene in the regulation of cell wall mannan and glucan biosynthesis. FEMS Yeast Res 3: 289-299. PMI: 12689636

Chauhan N, Inglis D, Roman E, Pla J, Li D, Calera JA, Calderone R (2003) Candida albicans response regulator gene SSK1 regulates a subset of genes whose functions are associated with cell wall biosynthesis and adaptation to oxidative stress. Eukaryot Cell 2: 1018-1024. PMI: 14555484

Chauhan N, Li D, Singh P, Calderone R, Kruppa M (2002) In Calderone R (ed.), Candida and Candidiasis. ASM Press, Washington DC, pp. 159-175.






Education


Ph.D (Molecular Biology), 2000, Jawaharlal Nehru University (JNU), New Delhi, India
M.Phil. (Biotechnology), 1994, University of Delhi, India
M.Sc. (Microbiology), 1990, AMU, Aligarh, UP, India
B.Sc. (Chemistry), 1987, Bareilly College, Rohilkhand University, Bareilly, UP, India


 
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