Molecular Biology of Infectious and Idiopathic Inflammation

Research in my lab is broadly directed at understanding the key events that cause inflammation during infection and autoimmune disorders. Uncontrolled inflammation contributes to the pathogenesis of inflammatory diseases as well as the development of cancers. We focus on model bacterial pathogen Salmonella Typhimurium with an ultimate goal to understand molecular mechanisms underlying the observed gastrointestinal (GI) inflammation.

The gram negative, facultative intracellular bacterial pathogen Salmonella is one of the most frequent causes of acute gastroenteritis in humans. The disease results from a complex cascade of interactions between the pathogenic bacterium, the host intestinal epithelium, the commensal microbiota and the immune system of the host. The disease manifestation is characterized histologically by massive infiltration of neutrophils (PMN), a phenotype also observed in some of the chronic recurrent inflammatory disorders with unknown etiology such as Crohn's disease (CD) and ulcerative colitis (UC). CD and UC are GI autoimmine disorders with very high incidence in developing and developed nations.

Using state of the art tools of microbiology, molecular biology and fluorescent-imaging, proteomics we intend to investigate complex mechanisms operational in the gut. Our lab utilises murine models, organotypic models and human patient samples to carry out these investigations. We have been examining the involvement of post-tranlational modification (PTMs) pathways in shaping inflammatory processes of gut. Our recent paradigm shifting discovery, demonstrating host-SUMOylation machinery perturbation by Salmonella using miRNAs has opened up several exciting avenues in biology of infectious diseases and GI illnesses. In future we aim to dissect the precise role of PTM pathways in governing epithelial-immune crosstalk particularly in the context of intestinal inflammation. The ultimate goal is not only to combat bacterial pathogenesis but also find therapeutic solutions to auto-immune disorders.

• Wellcome-DBT Intermediate Fellow

• Smriti Verma
  Young Investigator
  smriti@rcb.ac.in
• Gayatree Mohapatra
  Junior Research fellow
  gayatree@rcb.res.in
• Salman Ahmad Mustfa
  Junior Research fellow
  salman@rcb.ac.in
• Sarika Rana
  Junior Research fellow
  sarika.rana@rcb.res.in
• Pharvendra Kumar
  Junior Research fellow
  pharvendra.k@rcb.res.in
• Syed Mohd. Aamir Suhail
  Junior Research fellow
  aamir.suhail@rcb.res.in
• Hridya Chandrasekar
  Junior Research fellow
  hridya@rcb.res.in
• Mukesh Kumar
  Post Doctoral
  mukeshsingh@rcb.res.in
• Sonalika Maurya
  Junior Research Fellow
  sonalika@rcb.res.in
• Preksha Gaur
  Junior Research Fellow
  preksha@rcb.res.in
• Dr. Prabhakar
  Young Investigator
  prabhakar@rcb.res.in
• Neha Yadav
  Junior Research Fellow
  neha.yadav@rcb.res.in

1. Suhail A, Rizvi ZA, Mujagond P, Ali SA, Gaur P, Singh M, Ahuja V, Awasthi A, Srikanth CV. (2019) DeSUMOylase SENP7-Mediated Epithelial Signaling Triggers Intestinal Inflammation via Expansion of Gamma-Delta T Cells. Cell Rep | 3522-3538
2. Yavvari PS, Verma P, Mustfa SA, Pal S, Kumar S, Awasthi AK, Ahuja V, Srikanth CV *, Srivastava A*, Bajaj A*. A nanogel based oral gene delivery system targeting SUMOylation machinery to combat gut inflammation. Nanoscale. 2019 Mar 14;11(11):4970-4986. (* co-corresponding authors)
3. Yadav K, Yavvari PS, Pal S, Kumar S, Mishra D, Gupta S, Mitra M, Soni V, Khare N, Sharma P, Srikanth CV, Kapil A, Singh A, Nandicoori VK, Bajaj A. Oral Delivery of Cholic Acid-Derived Amphiphile Helps in Combating Salmonella-Mediated Gut Infection and Inflammation. Bioconjug Chem. 2019 Mar 20;30(3):721-732.
4. Mohapatra G, Gaur P, Mujagond P, Singh M, Rana S, Pratap S, Kaur N, Verma S, Krishnan V, Singh N, Srikanth CV. A SUMOylation-dependent switch of RAB7 governs intracellular life and pathogenesis of Salmonella Typhimurium. J Cell Sci. 2019 Jan 11;132(1).
5. Awasthi A, Kumar P, Srikanth CV, Sahi S, Puria R. Invitro Evaluation of Torin2 and 2, 6-Dihydroxyacetophenone in Colorectal Cancer Therapy. Pathol Oncol Res. 2019 Jan;25(1):301-309.
6. Mustfa SA, Singh M, Suhail A, Mohapatra G, Verma S, Chakravorty D, Rana S, Rampal R, Dhar A, Saha S, Ahuja V, Srikanth CV (2017) SUMOylation pathway alteration coupled with downregulation of SUMO E2 enzyme at mucosal epithelium modulates inflammation in inflammatory bowel disease. Open Biol 7: 170024
7. Srikanth CV, Verma S (2017) Sumoylation as an Integral Mechanism in Bacterial Infection and Disease Progression. Adv Exp Med Bio 963:389
8. Verma S, Srikanth CV. (2015)  Understanding the complexities of Salmonella-host crosstalk as revealed by in vivo model organisms. IUBMB Life 67:482.
9. Verma S, Mohapatra G, Ahmed SM, Rana S, Jain S, Khalsa JK, Srikanth CV. (2015)  Salmonella engages host microRNAs to modulate SUMOylation: a new arsenal for intracellular survival. Mol Cell Biol.Jun 22. pii: MCB.00397-15. [Epub ahead of print] PubMed PMID: 26100020.
10. Hallstrom KN, Srikanth CV, Agbor TA, Dumont CM, Peters KN, Paraoan L, Casanova JE, Boll EJ, McCormick BA (2015) PERP, a host tetraspanning membrane protein, is required for Salmonella-induced inflammation. Cell Microbiol. Jun;17(6):843-59. doi: 10.1111/cmi.12406. Epub 2015 Jan 24. PubMed PMID: 25486861.
11. Srikanth CV, Mercado-Lubo R, Hallstrom K, McCormick BA. (2011) Salmonella effector proteins and host-cell responses. Cell Mol Life Sci 68(22):3687.
12. Wall DM, Srikanth CV, McCormick BA. (2010) Targeting tumors with salmonella Typhimurium- potential for therapy. Oncotarget 1(8):721.
13. Srikanth CV, Wall, DM, Ana Maldonado-Contreras, Haining Shi, Daoguo Zhou, Zachary Demma, Mumy, KL, McCormick BA. (2010) Salmonella pathogenesis and processing of secreted effectors by caspase- 3. Science 330:390.
14. Johnson EE, Srikanth CV, Sandgren A, Harrington L, Trebica E, Wang L, Borregaard N, Murray M, Cherayil BJ. (2010) Siderocalin inhibits the intracellular replication of Mycobacterium tuberculosis in macrophges. FEMS Immunolo Med Microbiol 58(1):138.
15. Kumar CM, Khare G, Srikanth CV, Tyagi AK, Sardesai AA, Mande SC. (2009) Facilated oligomerization of Mycobacterial GroEL: Evidence for Phosphorylation-mediated oligomerization J Bacteriol 191(21):6525.
16. Kaur J, Srikanth CV, Bachhawat AK. (2009) Differential roles played by the native cysteine residues of the yeast glutathione.transporter, Hgt1p. Manuscript accepted for publication in FEMS Yeast Res 9(6):849.
17. Srikanth CV,  McCormick BA. (2008) Interactions of the Intestinal Epithelium with the Pathogen and the Indigenous Microflora: A Three Way Crosstalk Interdiciplinary perspective of Infectious diseases. 626827:1.
18. Harrington L, Srikanth CV, Antony R, Rhee SJ, Mellor AL, Shi HN, Cherayil BJ. (2008) Deficiency of indoleamine 2,3-dioxygenase enhances commensal-induced antibody responses and protects against Citrobacter rodentium-induced colitis. Infect Immun 76(7):3045.
19. Harrington L, Srikanth CV, Antony R, Shi HN, Cherayil BJ. (2007) A role for natural killer cells in intestinal inflammation caused by infection with Salmonella enterica serovar Typhimurium. FEMS Immunol Med Microbiol 51(2):372.
20. Srikanth CV, Cherayil BJ. (2007) Intestinal innate immunity and the pathogenesis of Salmonella enteritis. Immunol Res 37(1):61.
21. Srikanth CV, Vats P, Bourbouloux A, Delrot S, Bachhawat AK. (2005) Multiple cis-regulatory elements and the yeast sulphur regulatory network are required for the regulation of the yeast glutathione transporter, Hgt1p. Curr Genet 47(6):345.
22. Srikanth CV, Chakraborti AK, Bachhawat AK. (2005) Acetaminophen toxicity and resistance in the yeast Saccharomyces cerevisiae. Microbiology 151(Pt 1):99-111.
23. Kohli DK, Srikanth CV, Bachhawat AK. (2004) A search tool for identification and analysis of conserved sequence patterns in Saccharomyces spp. orthologous promoter. In Silico Biol 4(4):411.
24. Zhang MY, Bourbouloux A, Cagnac O, Srikanth CV, Rentsch D, Bachhawat AK, Delrot S. (2004) A novel family of transporters mediating the transport of glutathione derivatives in plants. Plant Physiol 134(1):482.
25. Ganguly D, Srikanth CV, Kumar C, Vats P, Bachhawat AK. (2003) Why is glutathione (a tripeptide) synthesized by specific enzymes while TSH releasing hormone (TRH or thyroliberin), also a tripeptide, is produced as part of a pherohormone protein?. IUBMB Life 55(9):553.