Gastroenterology, Hepatology and Nutrition
Gandhi Lab

Gandhi Research Lab

Liver Injury Research

The Gandhi laboratory is investigating mechanisms of liver injury with specific focus on hepatic stellate cells (HSCs). HSCs (8-10% of liver cell population) are the major cell type to cause liver fibrosis, but they also have a unique ability to induce acute liver injury directly by producing numerous cytokines and chemokines, and also by modulating characteristics of resident and infiltrating immune and inflammatory cells. The current focus of this program is to delineate precise mechanisms by which HSCs orchestrate inflammatory and immunological responses in the liver using a novel mouse model of HSC depletion (developed in our laboratory) and co-culture techniques.

Steatohepatitis Research

The other research program investigates the mechanisms of steatohepatitis and its sequel (fibrosis, cirrhosis and cancer) due to hepatocyte-specific deficiency of a protein named Augmenter of Liver Regeneration (ALR).  Liver (hepatocyte)-specific ALR-knockout of ALR in mouse was found to induce mitochondrial dysfunction, and progressive nonalcoholic steatohepatitis (NASH) with characteristics very similar to the human NASH. Our group has also observed that the hepatic ALR levels are lower in human NASH. The focus of this research is to discover link between ALR gene polymorphism(s) or anomaly in ALR protein and predisposition to develop aggressive form of NASH. 

Publications

Sharma, A; Wang, J; Gandhi, CR. CD14 is not required for carbon tetrachloride-induced hepatic inflammation and fibrosis with or without lipopolysaccharide challenge. Journal of Cellular Physiology. 2023; 238:1530-1541.

Rani, R; Gandhi, CR. Stellate cell in hepatic inflammation and acute injury. Journal of Cellular Physiology. 2023; 238:1226-1236.

Sharma, A; Kudira, R; Wang, J; Miethke, A; Gandhi, CR. Differential recruitment of monocyte-derived macrophages in control and stellate cell-depleted mice during recurrent carbon tetrachloride-induced acute liver injury. Journal of Cellular Physiology. 2022; 237:4215-4225.

Verma, AK; Sharma, A; Subramaniyam, N; Gandhi, CR. Augmenter of liver regeneration: Mitochondrial function and steatohepatitis. Journal of Hepatology. 2022; 77:1410-1421.

Rani, R; Sharma, A; Wang, J; Kumar, S; Polaki, US; Gandhi, CR. Endotoxin-Stimulated Hepatic Stellate Cells Augment Acetaminophen-Induced Hepatocyte Injury. The American journal of pathology. 2022; 192:518-535.

Lindquist, DM; Fugate, EM; Wang, J; Sharma, A; Gandhi, CR; Dillman, JR. MRI Measures of Murine Liver Fibrosis. Journal of Magnetic Resonance Imaging. 2021; 54:739-749.

McNelis, K; Yodoshi, T; Divanovic, S; Gandhi, C; Kim, JH; Anton, CG; Trout, AT; Mouzaki, M. Hepatic Steatosis in Infancy: The Beginning of Pediatric Nonalcoholic Fatty Liver Disease?. 2021; 2:e113.

Sharma, A; Verma, AK; Kofron, M; Kudira, R; Miethke, A; Wu, T; Wang, J; Gandhi, CR. Lipopolysaccharide Reverses Hepatic Stellate Cell Activation Through Modulation of cMyb, Small Mothers Against Decapentaplegic, and CCAAT/Enhancer-Binding Protein C/EBP Transcription Factors. Hepatology. 2020; 72:1800-1818.

Kumar, S; Verma, AK; Rani, R; Sharma, A; Wang, J; Shah, SA; Behari, J; Salazar Gonzalez, R; Kohli, R; Gandhi, CR. Hepatic Deficiency of Augmenter of Liver Regeneration Predisposes to Nonalcoholic Steatohepatitis and Fibrosis. Hepatology. 2020; 72:1586-1604.

Verma, AK; Gandhi, CR. Reply. Hepatology. 2020; 72:1157-1158.

Song, K; Kwon, H; Han, C; Chen, W; Zhang, J; Ma, W; Dash, S; Gandhi, CR; Wu, T. Yes-Associated Protein in Kupffer Cells Enhances the Production of Proinflammatory Cytokines and Promotes the Development of Nonalcoholic Steatohepatitis. Hepatology. 2020; 72:72-87.

Gandhi, CR. Pro- and Anti-fibrogenic Functions of Gram-Negative Bacterial Lipopolysaccharide in the Liver. Frontiers in Medicine. 2020; 7:130.

Kumar, S; Rani, R; Verma, AK; Sharma, A; Wang, J; Gonzalez, RS; Shah, SA; Behari, J; Kohli, R; Gandhi, CR. Deficiency of Augmenter of Liver Regeneration is Critical Predisposing Factor for Nonalcoholic Steatohepatitis and Fibrosis. The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2020; 34:1.

Kumar, S; Rani, R; Karns, R; Gandhi, CR. Augmenter of liver regeneration protein deficiency promotes hepatic steatosis by inducing oxidative stress and microRNA-540 expression. The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2019; 33:3825-3840.

Flood, HM; Bolte, C; Dasgupta, N; Sharma, A; Zhang, Y; Gandhi, CR; Kalin, TV; Kalinichenko, VV. The Forkhead box F1 transcription factor inhibits collagen deposition and accumulation of myofibroblasts during liver fibrosis. Biology Open. 2019; 8:bio039800.

Contact Us

Chandrashekhar Gandhi.
Chandrashekhar R. Gandhi, MSc, PhD
Professor, Department of Pediatrics

Mailing address:

Division of Gastroenterology, Hepatology and Nutrition
3333 Burnet Ave. 
MLC 2010 
Cincinnati, OH 45229-3039 

Lab: Location T, Rooms T9.433 and T9.462 

Office: Location T, Suite T9.480

Phone: 513-517-1090 
Email: chandrashekhar.gandhi@cchmc.org