Venkatakrishna Rao JALA Lab

About

Dr. Jala's primary research focus centers on comprehending the regulation and mechanisms of gut barrier function, inflammation, microbiota, and microbial metabolites (such as urolithins) in inflammatory disorders like inflammatory bowel diseases (IBD), alcohol liver disease (ALD), and colon cancer. Additionally we also focus on mitigating the toxic effects environmental toxins such as arsenic on gut barrier using microbial metabolites such as urolithin A. Our laboratory is also investigates how to improve the immune check point inhibitor (ICI)-mediated colitis and immune related adverse events (irAEs) during cancer immunotherapies. It is increasingly evident that alterations in the environment, diet, and genetic factors play a significant role in shaping human microbiota, thereby influencing the progression of various diseases.

To unravel these intricate connections, our research employs a multifaceted approach, leveraging genetically modified transgenic/compound (knockout/conditional expression of relevant genes, germ-free and gnotobiotic mice) pre-clinical mouse models along with cellular and molecular models. Additionally, we utilize advanced next-generation sequencing and metabolomics methods to delve into the intricate roles of microbiota and their metabolites in human pathophysiology.

Key Research Areas

Determining the impact of gut microbial metabolites on gut barrier function and inflammation, especially in IBD, AALD and colon cancer.
Unraveling mechanisms of urolithin A in modulating gut barrier function through crosstalk between epithelium and immune cells,
Investing the role of microbial metabolites in improving efficacies of cancer chemotherapy (chemoresistance cancer) and ICI-immunotherapy.
Determining functional microbiota in regulating AALD and IBD.
Examining impact of environmental toxic metal arsenic on gut barrier dysfunction and establishing metabolite-based therapeutics to mitigate toxic effects.
Attenuation of ICI-mediated immune related adverse events especially colitis.

Team

Dr. Sweta Ghosh, Post-doctoral associate, sweta.ghosh@louisville.edu
Ms. Fariha Nasme, Student, fariha.nasme@louisville.edu
Mr. Temitope Aderanti, Research Technician, temitope.aderanti@louisville.edu

Recent Publications

Ghosh S, Erickson D, Chua MJ, Collins J*, Jala VR*. The microbial metabolite urolithin A reduces Clostridioides difficile toxin expression and toxin-induced epithelial damage. mSystems. 2024;9(2):e0125523. Epub 20240109. doi: 10.1128/msystems.01255-23. PubMed PMID: 38193707; PMCID: PMC10878087.
Ghosh S, Banerjee M, Haribabu B, Jala VR. Urolithin A attenuates arsenic-induced gut barrier dysfunction. Arch Toxicol. 2022;96(4):987-1007. Epub 20220205. doi: 10.1007/s00204-022-03232-2. PubMed PMID: 35122514.
Ghosh S, Moorthy B, Haribabu B, Jala VR. Cytochrome P450 1A1 is essential for the microbial metabolite, Urolithin A-mediated protection against colitis. Front Immunol. 2022;13:1004603. Epub 20220908. doi: 10.3389/fimmu.2022.1004603. PubMed PMID: 36159798; PMCID: PMC9493474.
Ghosh S, Singh R, Vanwinkle ZM, Guo H, Vemula PK, Goel A, Haribabu B, Jala VR. Microbial metabolite restricts 5-fluorouracil-resistant colonic tumor progression by sensitizing drug transporters via regulation of FOXO3-FOXM1 axis. Theranostics. 2022;12(12):5574-95. Epub 20220718. doi: 10.7150/thno.70754. PubMed PMID: 35910798; PMCID: PMC9330515.
Ghosh S, Whitley CS, Haribabu B, Jala VR. Regulation of Intestinal Barrier Function by Microbial Metabolites. Cell Mol Gastroenterol Hepatol. 2021. Epub 2021/02/22. doi: 10.1016/j.jcmgh.2021.02.007. PubMed PMID: 33610769.
Singh R, Chandrashekharappa S, Bodduluri S, Baby B, Hegde B, Kotla N, Hiwale A, Saiyed T, Patel P, Vijay-Kumar M, Langille G, Douglas G, Cheng X, Rouchka R, Waigel S, Dryden G, Alatassi H, Zhang HG, Haribabu B, Vemula P*, Jala VR* Enhancement of Gut Barrier Integrity by a Microbial Metabolite through Nrf2 Pathway, Nat Commun. 2019;10(1):89. doi: 10.1038/s41467-018-07859-7. PubMed PMID: 30626868