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Dr. Manjula Kalia

Associate Professor
E-mail: manjula at rcb dot res dot in

  • Ph.D. 1998, National Institute of Immunology, New Delhi
  • Post-Doctoral Fellow, University of Calgary, Canada
  • Visiting Fellow & DST-Fast Track Scientist, NCBS, Bangalore
  • DBT-IYBA Scientist, ICGEB, New Delhi
  • Research Scientist D/E, VIDRC, THSTI, Faridabad

Interactions of Flaviviruses with host cellular mechanisms and implications for pathogenesis

Host-pathogen interaction is a series of complex and intertwined cellular and signalling events that determine disease outcome. Understanding these interactions is crucial for identification and development of therapies, vaccines and anti-viral drugs. Our research theme is to understand how Flaviviruses [positive-stranded RNA viruses- Japanese Encephalitis Virus (JEV) and Dengue virus] interact with and modulate cellular pathways to establish infection. Both viruses are spread by infected mosquito bites and pose a significant health burden for India. We aspire to understand the mechanisms leading to disease, identify & validate drug-targets, develop therapeutics and improve vaccine efficacy.

Our focus is the host Membrane trafficking, Autophagy and ER-associated degradation (ERAD) pathway.

Our studies on the membrane trafficking requirements for JEV infection have shown how the virus can exploit alternate endocytic pathways (clathrin independent) depending on the target cell (neuronal vs epithelial). This has enabled us to identify novel drug-targets that are in the process of being validated. Autophagy, a basic cellular housekeeping pathway, is closely linked to virus pathogenesis. Our studies have highlighted the role of this pathway as an anti-viral defence mechanism, and its modulation by oxidative and ER stress. Interestingly, some autophagy proteins play an independent role in virus replication.

Our current research themes are-

  • Molecular Regulation of Autophagy & ERAD pathway during virus infection
  • Mechanisms of the anti-viral role of autophagy
  • Regulation and enhancement of immune response to virus infection by autophagy modulation
  • Validation of drug targets against flavivirus infections in vitro and in animal model
  • SERC Fast Track Fellowship for Young Scientists (DST) 2003-2006
  • Innovative Young Biotechnologist Award (DBT) 2007-2010
  1. Manish Sharma, Kiran Bala Sharma, Shailendra Chauhan, Sankar Bhattacharyya, Sudhanshu Vrati, Manjula Kalia (2018) “Diphenyleneiodonium enhances oxidative stress and inhibits Japanese encephalitis virus induced autophagy and ER stress pathways” Biochem Biophys Res Commun. 2018 May 22. pii: S0006-291X(18)31218-X. doi: 10.1016/j.bbrc.2018.05.149. [Epub ahead of print] PMID:29792860
  2. Vikas Sood, Kiran Bala Sharma, Vishal Gupta, D Saha, P Dhapola, Manish Sharma, Utsav Sen, S. Kitajima, S Chowdhury, Manjula Kalia, Sudhanshu Varti (2017) “ATF3 negatively regulates cellular antiviral signaling and autophagy in the absence of type I interferons” Scientific Reports 2017 Aug 18;7(1):8789. Doi:10.1038/s41598-017-08584-9. PMID: 28821775
  3. A Madhvi, S Hingane, R Srivastav, N Joshi, C Subramani, R Muthumohan, R Khasa, S Varshney, Manjula Kalia, Sudhanshu Vrati, Milan Surjit, Ranjith-Kumar CT (2017) “A screen for novel hepatitis C virus RdRp inhibitor identifies a broad-spectrum antiviral compound” Scientific Reports 2017 Jul 10;7(1): 5816. Doi: 10.1038/s41598-017-04449-3. PMID: 28725041
  4. 4. Manish Sharma, Sankar Bhattacharyya, Kiran Bala Sharma, Shailendra Chauhan, Suramya Asthana, Mailk Zainul Abdin, Sudhanshu Vrati and Manjula Kalia (2017) “Japanese encephalitis virus activates autophagy through XBP1 and ATF6 ER stress sensors in neuronal cells” Journal of General Virology 2017 May;98(5):1027-1039. doi: 10.1099/jgv.0.000792. Epub 2017 May 23. PMID: 28535855
  5. 5. Minu Nain, Sriparna Mukherjee, Sonali Porey Karmakar, Adrienne W. Paton, James C. Paton, M.Z. Abdin, Anirban Basu, Manjula Kalia*, Sudhanshu Vrati* (2017) “GRP78 is an Important Host Factor for Japanese Encephalitis Virus Entry and Replication in Mammalian Cells” Journal of Virology 2017 Feb 28;91(6). pii: e02274-16. doi: 10.1128/JVI.02274-16. Print 2017 Mar 15. PMID: 28053106
  6. 6. Daniel J. Klinosky et al., Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) Autophagy 2016 Jan 2:12(1): 1-222
  7. 7. Minu Nain, M.Z.Abdin, Manjula Kalia* and Sudhanshu Vrati* (2015) “Japanese encephalitis virus invasion of cell: allies and alleys” Reviews in Medical Virology 2015 Dec23:doi:10.1002/rmv.1868 [Epub ahead of print] [*Co-corresponding Author]
  8. 8. Nimesh Gupta, Melissanne de Wispelaere, Maxime Lecerf, Manjula Kalia, Tobias Scheel, Sudhanshu Vrati, Claudia Berek, Srinivas V. Kaveri, Philippe Despres, Sebastien Lacroix-Desmazes, Jordan D. Dimitrov (2015) “Neutralization of Japanese Encephalitis Virus by heme-induced broadly reactive human monoclonal antibody” Scientific Reports. 2015 Nov6:5:16248. Doi: 10.1038/srep16248
  9. 9. Deepika Bhullar, Richa Jalodia, Manjula Kalia, Sudhanshu Vrati (2014) “Cytoplasmic Translocation of Polypyrimidine Tract-Binding Protein and Its Binding to Viral RNA during Japanese Encephalitis Virus Infection Inhibits Virus Replication” PLoS ONE 9(12):e114931. doi:10.1371/journal.pone.0114831
  10. 10. Manish Sharma, Sankar Bhattacharyya, Minu Nain, Manpreet Kaur, Vikas Sood, Vishal Gupta, Renu Khasa, Malik Abdin, Sudhanshu Vrati* and Manjula Kalia* (2014) “Japanese Encephalitis Virus Replication is Negatively Regulated by Autophagy and Occurs on LC3-I- and EDEM1-containing Membranes. Autophagy. 2014 Sep; 10(9): 1637-51. Doi: 10.4161/auto.29455. Epub 2014 July16
  11. 11. Nimesh Gupta, Pushpa Hegde, Maxime Lecerf, Minu Nain, Manpreet Kaur, Manjula Kalia, Sudhanshu Vrati, Jagadeesh Bayry, Sebastien Lacroix-Desmazes and Srini V. Kaveri (2014) “Japanese encephalitis virus expands regulatory T cells by increasing the expression of PD-L1 on dendritic cells” Eur.J.Immunol. 2014 May;44(5):1363-74. [Epub 2014 Mar24]
  12. 12. Manjula Kalia*, Renu Khasa, Manish Sharma, Minu Nain and Sudhanshu Vrati (2013) “Japanese Encephalitis Virus Infects Neuronal Cells through a Clathrin Independent Endocytic Mechanism” J Virology. 2013 Jan; 87(1):148-162. [Epub 2012 Oct 10]. [*Corresponding Author]
  13. 13. Vivek Chandra, Manjula Kalia, Krishan Hajela and Shahid Jameel (2010) “The ORF3 protein of hepatitis E virus delays degradation of activated growth factor receptors by interacting with CIN85 and blocking formation of the Cbl-CIN85 complex” J Virology. 2010 Apr; 84(8):3857-67. [Epub 2010 Feb 3].
  14. 14. Manjula Kalia and Shahid Jameel (2011) Virus entry paradigms. Amino Acids Nov; 41(5):1147-57. [Epub 2009 Oct 15]. Review
  15. 15. Manjula Kalia*, Vivek Chandra, Sheikh Abdul Rahman, Deepak Sehgal and Shahid Jameel (2009) “Heparan Sulfate Proteoglycans are Required for Cellular Binding of the Hepatitis E Virus ORF2 Capsid Protein and for Viral Infection” J. Virology Vol 83, No24:12714-24 [Epub 2009 Oct7]. [*Corresponding Author]
  16. 16. Vivek Chandra, Shikha Taneja, Manjula Kalia and Shahid Jameel (2008) “Molecular Biology and Pathogenesis of Hepatitis E Virus” J.Biosciences 33:451-64
  17. 17. Manjula Kalia, Sudha Kumari, Rahul Chadda, Michelle M. Hill, Robert G. Parton, and Satyajit Mayor (2006) “Arf6-independent GEECs fuse with sorting endosomes via a Rab5/PI-3’ kinase dependent machinery” Mol Biol Cell 17: 3689-3704
  18. 18. M. Awasthi-Kalia, K.V. Bhat and R.K. Anand. (2002) “Genetic characterization of Mus musculus and related forms from India”. Experimental Animals 51: No 1. 103-107
  19. 19. M. Mishra, N. Dubey, S.M. Totey, K.V. Bhat, S. Babu, M. Awasthi-Kalia and R.K. Anand. (2002) “Phylogenetic relationships and genetic polymorphisms in wild Indian mice”. Biomolecular Engineeering 18: No 6. 281-288
  20. 20. M. Awasthi-Kalia, P.P.M. Schnetkamp and J.P. Deans. (2001). “Differential effects of Filipin and Methyl--cyclodextrin on B Cell Receptor Signaling”. Biochemical and Biophysical Research Communications 287: 77-82
  21. 21. R.J. Petrie, P.P.M. Schnetkamp, K.D. Patel, M. Awasthi-Kalia and J.P. Deans. (2000) "Transient Translocation of the B Cell Receptor and Src Homology 2 Domain- Containing Inositol Phosphatase to Lipid Rafts: Evidence Toward a Role in Calcium Regulation". Journal of Immunology. 165: 1220-1227
  22. 22. M. Awasthi, K.V. Bhat and R.K. Anand. (1999) "Allozyme variation in four Indian species of genus Mus: A comparative analysis ". Journal of Genetics. 78: No 2. 73-80
  23. 23. M. Awasthi, S. Rath, P.A. Cazenave and R.K. Anand. (1999) "TCR V 17 gene polymorphism in the Indian Mus musculus". Journal of Biosciences. 24: 163-169
  24. 24. M. Awasthi, K.V. Bhat and R.K. Anand. (1998) "Genetic heterogeneity in the Indian Mus musculus". Biochemical Genetics. 36: Nos. 7/8 245-258.

 

Dr. Manjula Kalia
Associate Professor
Regional Centre for Biotechnology
NCR Biotech Science Cluster
3rd Milestone, Faridabad-Gurgaon Expressway
P.O. Box No. 3, Faridabad - 121 001
Haryana (NCR Delhi), India
E-mail: manjula at rcb dot res dot in
Phone: 91 129-2848853

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