- PhD in Yeast Molecular Genetics (1996-2001): School of Life Sciences, Jawaharlal Nehru University, New Delhi.
- Bsc Biochemistry (Hons.) (1989-1992): Sri Venkateswara College, University of Delhi
- Msc Biochemistry (1992-1994): University of Delhi South Campus
Candida albicans is a natural component of the human flora that can cause life-threatening infections in immunosuppressed patients. Treatment of fungal infections is a challenge due to the limited repertoire of available antifungals. Additionally, both the planktonic as well as biofilm modes of growth of C. albicans develop resistance to existing azole antifungals due to the upregulation of drug efflux pumps, posing a challenge in treating Candida infections. This necessitates the need to identify additional cellular targets for antifungal therapy. In this context, our lab focuses on dissecting various cellular processes that are regulated by the mitochondria and the seven-transmembrane receptor family of proteins (Rta2, Rta3 and Rta4), in an attempt to identify features that are unique to C. albicans. We propose that targeting the mitochondria and the Rta family of proteins will increase the antifungal target space and will provide powerful strategy to treat fungal infections. We have shown that mitochondria are required for modulating drug resistance, lipid homeostasis, Hog1-mediated oxidative stress pathway, iron homeostasis and ergosterol levels in C. albicans.
The Rta1-like family in S. cerevisiae was initially named LTE, for lipid-translocating exporter, based on the finding that Rsb1 is involved in the release of sphingoid bases. In C. albicans Rta1 family of proteins are unique to fungal kingdom and can be considered as potential therapeutic targets. Functional analysis of the Rta1 family of proteins has revealed their importance in regulating a plethora of functions such as modulating ER stress response and asymmetric distribution of phosphatidylcholine across the plasma membrane. Additionally we show that all these proteins are involved in regulating biofilm formation in C. albicans. Considering that biofilm-specific drugs do not exist in C. albicans, targeting these genes may have therapeutic implications that may contribute to the development of biofilm-specific antifungals.
The upregulation of the drug efflux pumps, Cdr1 and Cdr2 in drug resistant C. albicans isolates is often accompanied by the simultaneous induction of a subset of genes (RTA3, IFU5 and HSP12) via the transcription factor Tac1. The significance of these co-regulated genes remains largely unexplored in C. albicans, which prompted us to ask if these proteins contribute to the development of azole resistance in C. albicans by affecting the function of Cdr1 and Cdr2. Thus, in order to investigate the relevance of Tac1 co-regulated genes, we characterized Ifu5, a WW domain-containing protein, in this pathogenic fungus. We demonstrate the role of Tac1-regulated Ifu5 in mediating normoxic and hypoxic responses in C. albicans. ifu5Δ/Δ cells display defects in cell wall physiology and hyphal morphogenesis under normoxia. Furthermore, we demonstrate that Ifu5 in alliance with the hypoxic regulator Efg1 may contribute to hypoxic adaptation in C. albicans.
Our laboratory has also made considerable progress in providing mechanistic insights into the functions of these aforesaid cellular novel antifungal targets.; all are unique to the fungal kingdom. We are currently interested in identifying compounds that will selectively inhibit the aforesaid proteins in C. albicans, paving a way for identifying new antifungals that may also be specific to the biofilm-based infections.
- Assistant Professor, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067.
- Research Associate, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067.
- Postdoctoral Fellow, University of Iowa, Iowa City, USA
- Postdoctoral Fellow, University of Minnesota, Twin Cities Campus, Minneapolis, USA
- Innovative Young Biotechnologist Award for 2007 (IYBA-2007) by Department of Biotechnology, Ministry of Science and Technology, Government of India.
- Awarded C. R. Krishnamurthy Young Scientist Award in 2000.
- Delhi University Gold Medal for standing first in M. Sc Biochemistry, University of Delhi, New Delhi in 1994
- Qualified the JRF/NET Fellowship awarded by the Council for Scientific and Industrial Research, Government of India in 1994.
- Qualified the Graduate Aptitude Test in Engineering (percentile score 99.14). All India Rank- 20 in 1994.
University of Madrid, Spain
John Hopkins, USA
University of Aberdeen, Aberdeen, UK
- Shabnam Sircaik, Elvira Roman, Priyanka Bapat, Keunsook K Lee, David Andes, Neil A. A. R. Gow, Clarrisa Nobile, Jesus Pla and Sneh Lata Panwar. The protein kinase Ire1 impacts pathogenicity of Candida albicans by regulating homeostatic adaptation to endoplasmic reticulum stress (2021). Cell microbiol, January 5.
- Sumit Rastogi, Lasse Van Wijlick, Shivani Ror, Keunsook K Lee, Elvira Roman, Pranjali Agarwal, Nikhat Manzoor, Neil A R Gow, Jesus Pla, Joachim Ernst and Sneh Lata Panwar. Ifu5, a WW domain-containing protein interacts with Efg1 to achieve coordination of normoxic and hypoxic functions to influence pathogenicity traits in Candida albicans (2020). Cell microbiol, Feb; 22(2):e13140. doi: 10.1111/cmi.13140.
- Shivani Ror and Sneh Lata Panwar. Sef1-regulated iron regulon responds to mitochondria-dependent iron-sulfur cluster biosynthesis in Candida albicans (2019). Front Microbiol, Jul 9;10:1528. doi: 10.3389/fmicb.2019.01528.
- Eijaz K Pathan, Vandana Ghormade, Sneh Lata Panwar, Rajendra Prasad, Mukund V Deshpande. Molecular studies of NAD- and NADP-glutamate dehydrogenase decipher the conundrum of yeast-hypha dimorphism in zygomycete Benjiminiella poitrasii (2019). FEMS yeast res Dec 1; 19(8). pii: foz074. doi: 10.1093/femsyr/foz074.
- Sonali Mishra, Sumit Kumar Rastogi, Sangeeta Singh, Sneh Lata Panwar, Manoj Kumar Shrivash, Krishna Misra. Controlling pathogenesis in Candida albicans by targeting Efg1 and Glyoxylate pathway through naturally occurring polyphenols (2019). Mol Bio Rep.
- Manoj K. Shirvash, Sonali Mishra, Sneh Lata Panwar, Shabnam Sircaik, Jyoti Pandey and Kirshna Misra. Attenuation of pathogenicity of Candida albicans by application of polyphenols (2018). J. of Microb & Biochem Technol, April 10; doi:104172/1948-5948.1000392.
- Archita Srivastava, Shabnam Sircaik, Farha Husain, Edwina Thomas, Shivani Ror, Sumit Rastogi, Darakshan Alim, Priyanka Bapat, David R Andes, Clarrisa Nobile and Sneh Lata Panwar. Distinct roles of the 7-transmembrane receptor protein Rta3 in regulating the asymmetric distribution of phosphatidylcholine across the plasma membrane and biofilm formation in Candida albicans (2017). Cell microbiol, 19(12). doi: 10.1111/cmi.12767.
- Edwina Thomas, Shabnam Sircaik, Elvira Roman, Steven Claypool, Jean-Michel Brunel, Jesus Pla and Sneh Lata Panwar.The activity of RTA2, a downstream effector molecule of the calcineurin pathway, is required for tunicamycin-induced ER stress response in Candida albicans (2015). FEMS Yeast Res. 15 pii: fov095. doi: 10.1093/femsyr/fov095.
- Nikhat Manzoor, Jesús Pla and Sneh Lata Panwar. Mitochondria Influence CDR1 Efflux Pump Activity, Hog1-Mediated Oxidative Stress Pathway, Iron Homeostasis, and Ergosterol Levels in Candida albicans (2013). Antimicrob Agents Chemother. 57: 5580-5599. Impact factor- 4.2
- Manoharlal, R., Gaur, NA., Panwar, SL., Morschhaeuser, J and Prasad, R. Transcriptional activation and increased mRNA stability contributes to overexpression of CDR1 in azole-resistant Candida albicans (2008). Antimicrob. Agents Chemother. 52: 1481-1492.
- Pasrija R, Panwar, SL., and Prasad R. CaCdr1p and CaMdr1p multidrug transporters of Candida albicans display different lipid specificities: both ergosterol and sphingolipids are essential for targeting of CaCdr1p to membrane rafts (2008). Antimicrob. Agents Chemother. 52: 694-704.
- Panwar, SL and Moye-Rowley WS. Long chain base tolerance in Saccharomyces cerevisiae in induced by retrograde signals from the mitochondria (2006). J. Biol. Chem. 281: 6376-6384.
- Zhang, X., Kolackowzsi, A., Deveaux, F., Panwar, SL*., Hallstrom TC., Jacq C. and Moye-Rowley WS. Transcriptional regulation by Lge1p requires a function independent of its role in histone H2B ubiquitination (2005). J. Biol. Chem. 280: 2759-2770.
* the first three authors contributed equally to this work
- Panwar, SL., Legrand, M., Dignard D., Whiteway, M. and Magee, P. T. MFα1, the Gene Encoding the α Mating Pheromone of Candida albicans (2003). Eukaryotic Cell. 2: 1350-1360.
- Panwar, SL., Krishnamurthy, S., Gupta, V., Alarco, A.–M., Raymond, M., Sanglard, D. and Prasad, R. CaALK8, an alkane assimilating cytochrome P450 confers multidrug resistance when expressed in a hypersensitive strain of Candida albicans (2001). Yeast 18:1117-1129.
- Krishnamurthy, S., Gupta, V., Panwar, SL and Prasad, R. Characterisation of human steroid hormone efflux mediated by Cdr1p, a multidrug transporter of Candida albicans, belonging to ABC super family (1998). FEMS Microbiol. Letts. 158: 69-74.
- Krishnamurthy, S., Chatterjee, U. Gupta, V., Prasad, R., Das, P., Panwar, SL., Hasnain, S. E. and Prasad, R. (1998). Deletion of transmembrane domain (TM) 12 of CDR1 a multidrug transporter from Candida albicans, leads to altered drug specificity: Expression of a yeast multidrug transporter in Baculovirus expression system. Yeast 14: 535-550.
- Krishnamurthy, S., Gupta, V., Panwar, SL and Prasad, R (1998). Expression of CDR1, multidrug resistance gene of Candida albicans: in vitro transcriptional activation by heat shock, drugs and human steroid hormones. FEMS Microbiol. Letts. 160: 191-197.
- Gupta, V., Kohli, A., Krishnamurthy, S., Puri, N., Aalamgeer, S. A., Panwar, S. and Prasad, R. (1998). Identification of polymorphic mutant alleles of CaMDR1, a major facilitator of Candida albicans, which confers multidrug resistance and its in vitro transcriptional activation. Curr. Genet. 34: 192-199.
- Darakshan Alim, Shabnam Sircaik and Sneh Lata Panwar. The significance of lipids to biofilm formation in Candida albicans: an emerging perspective (2018). J. of Fungi, 4. Doi:10.3390/jof4040140.
- Sneh Lata Panwar, Ritu Pasrija and Rajendra Prasad (2008). Membrane homeostasis and multidrug resistance in yeast. Biosci Rep, 28: 217-228.
- R. Prasad and Sneh Lata Panwar (2004) Physiological relevance of multidrug transporters in yeasts. Curr Sci, 86: 1.
- R. Prasad and Sneh Lata Panwar and Smriti (2001) Drug resistance in yeasts- An emerging scenario. Adv Microb. Physiol. 46: 156-189.
- R. Prasad., S. KrishnaMurthy, V. Gupta and Sneh Lata Panwar (1998) Multidrug transporters of Candida albicans. Folia Microbiol. 43, 228.
- R. Prasad, S. KrishnaMurthy, Ramasare Prasad, Vinita Gupta and Sneh Lata Panwar (1996). Multidrug resistance: an emerging threat. Curr. Sci. 71, 205-213.
- Hina Sanwal, Sneh Lata Panwar and Rajendra Prasad. ATP-binding cassette (ABC) transporters in yeasts, their role in multidrug resistance and survival. In: ABC transporters in microorganisms: Research, innovation and value as targets against drug resistance. Alicia Ponte-Sucre (Ed), Caister Academic Press (2009).
- R. Prasad, Sneh Lata Panwar and S. Krishnamurthy. Drug resistance mechanisms of human pathogenic fungi. In: Fungal Pathogenesis: Principles and Clinical Applications., R. Cihlar and R. A. Calderone, (Eds).Marcel Dekker (2001).
- R. Prasad, Sneh Lata Panwar and Neeti Puri. Sex and drug ATPases in yeasts. In: Biophysical Processes in Living systems., P. Pardha Saradhi Ed. Oxford and IBH Publishing Co. Pvt. Ltd. (2001).
Sponsoring Agency: Defense Research Development & Organization
Title: Screening for drugs against the Endoplasmic Reticulum stress-responsive Rta proteins of Candida albicans for antifungal therapy: implications in wound infections. Duration: 2019 - 2022
Sponsoring Agency: Indian Council of Medical Research
Title: Establishing the phospholipid flippase subunit Lem3 as a novel co-target for circumventing resistance to existing antifungals in Candida albicans.
Duration: 2020 - 2023