Research focuses on elucidation of molecular pathways at cellular and systems level during disease progression using integrated analysis of genomic (total RNA, miRNA), proteomic, metabolomic and metagenomics. The groups aim is to tease out the effects of microbial variations structurally in composition and functionally at metabolic levels during disease onset and therapy. Using the Next Generation Sequencing tools the group has analyzed the gut metagenome in patients of alcoholic liver disease. This information, further, being correlated with the PBMC transcriptome and plasma Faculty metabolome to determine the pathophysiological pathways. New tools are being developed for identifying transcriptome modules in blood and liver, that provide insight at a system level functioning of genes/cells during disease progression. The strongholds of the lab are employing mathematical modelling for analysis of the omics data as it is the only unit at ILBS to integrate biology with bioinformatic analysis, using R, Python, Java and other tools. Another area of investigation is genetic analysis of inheritance patterns of the potential candidate genes which when mutated results in genetic disorders which finally affect the liver functioning. The group has screened affected families to identify potentially susceptible individuals by mutation analysis screening in NAFLD. The group additionally implements machine learning algorithms for deeper understanding of role of genes, proteins, metabolite and microbes in disease progression and remission.

PhD – University of Delhi - 2004
Postdoctoral: Department of Urology, Vanderbilt University, Nashville, TN, USA,Department of Microbiology, Meharry Medical College, Nashville, TN, USA,Division of Digestive Diseases, Emory University, Atlanta, GA, USA,Division of Gastroenterology and Hepatology, University of Maryland, Baltimore, MD, USA

Member:

European Association for the Study of the Liver

The Asian Pacific Association for the Study of the Liver

The goal of the Systems Biology Laboratory (SBL) at ILBS is to progress the understanding of underlying mechanisms in liver diseases by employing a systems approach. The laboratory has a rare distinction in working on molecular mechanisms from cellular (hepatocytes and others) to ecosystem levels (gut microbiome) with focus on:

• Unravelling the molecular pathways active between cells and tissues during disease progression using the “Omics” approach. For this we use an integrated approach of genomic, proteomic, metabolomic and metagenomic tools. An intense area of research in this regard is the genetic analysis of inheritance patterns of the potential candidate genes which when mutated results in genetic disorders which finally affect the liver functioning. Our group has screened affected families to identify potentially susceptible individuals by mutation analysis screening.
• Importance of gut microbiota in diseases : Human body can now be recognized as a fully functional ecosystem, with microbes having an integral role in its functioning. With recent attention on the importance of gut microbiota in diseases, the gut-liver axis needs to be studied in detail to determine the role these microbes play in maintaining a healthy liver or progression towards disease. Using the Next Generation Sequencing tools the group has analyzed the gut metagenome of chronic alcoholic patients. Microbiota variability and association to disease is an active project for fatty liver disorders. Modification of microbiota by dietary alterations is currently being investigated in diseased patients as well as animal models of liver disease.
• At the cellular level, the lab is involved in determining the role of autophagy and endoplasmic reticulum stress in hepatic disorders like non-alcoholic fatty liver disease (NAFLD), fibrosis, hepatocellular carcinoma (HCC) and other metabolic disorders. Both these processes are well integrated and have been implicated as protective in smaller perturbations but destructive with continuous stress on the cells. Our aim is to determine the tripping point where these pathways shift from a protective to a destructive mode. At the sub-cellular level, the mitochondrial protein translocases are under investigation for their role in maintenance of the health of both normal and carcinomatous hepatocytes. The aim of the project is to determine the modification in mechanism of these beta barrel proteins in regulating the function of the mitochondria in healthy and diseased hepatocytes.
• The group is deeply engaged in devising computational strategies for analysis of the multi-omic data generated by proteomic, metabolomic, metagenomic high throughput techniques. We implement machine learning algorithms (as suited for the study) over various platforms like R, Python, and other.

Geomics, Metagenomics, Transcriptomics, Metabolomics, Proteomics, Computational Biology, Systems Biology

• 1. Biomolecular map of albumin identifies signatures of severity and early mortality in acute liver failure. Sharma N, Pandey S, Yadav M, Mathew B, Bindal V, Sharma N, Tripathi G, Bhat SH, Gupta A, Maiwall R, Sharma S, Sarin SK, Maras JS.
  J Hepatol. 2023 Sep;79(3):677-691. doi: 10.1016/j.jhep.2023.04.018. Epub 2023 Apr 26. PMID: 37116716
• 2. Fecal microbiota transplantation compared with prednisolone in severe alcoholic hepatitis patients: a randomized trial.Pande A, Sharma S, Khillan V, Rastogi A, Arora V, Shasthry SM, Vijayaraghavan R, Jagdish R, Kumar M, Kumar G, Mondot S, Dore J, Sarin SK. Hepatol Int. 2023 Feb;17(1):249-261. doi: 10.1007/s12072-022-10438-0. Epub 2022 Dec 5.PMID: 36469298 Clinical Trial.
• 3. Healthy Donor Fecal Microbiota Transplantation in Steroid-Ineligible Severe Alcoholic Hepatitis: A Pilot Study. Philips CA, Pande A, Shasthry SM, Jamwal KD, Khillan V, Chandel SS, Kumar G, Sharma MK, Maiwall R, Jindal A, Choudhary A, Hussain MS, Sharma S, Sarin SK. Clin Gastroenterol Hepatol. 2017 Apr;15(4):600-602. doi: 10.1016/j.cgh.2016.10.029. Epub 2016 Nov 2. PMID: 27816755 Review. No abstract available.
• 4. Global metabolome profiling of COVID-19 respiratory specimen using high-resolution mass spectrometry (HRMS). Sharma N, Bhat SH, Tripathi G, Yadav M, Mathew B, Bindal V, Sharma S, Gupta E, Maras JS, Sarin SK. STAR Protoc. 2022 Mar 18;3(1):101051. doi:10.1016/j.xpro.2021.101051. Epub 2021 Dec 3. PMID: 34877545 Free PMC article.
• 5. Iron-Overload triggers ADAM-17 mediated inflammation in Severe Alcoholic Hepatitis. Maras JS, Das S, Sharma S, Sukriti S, Kumar J, Vyas AK, Kumar D, Bhat A, Yadav G, Choudhary MC, Sharma S, Kumar G, Bihari C, Trehanpati N, Maiwall R, Sarin SK. Sci Rep. 2018 Jul 6;8(1):10264. doi: 10.1038/s41598-018-28483-x. PMID: 29980709 Free PMC article.
• 6. Protocol for global proteome, virome, and metaproteome profiling of respiratory specimen (VTM) in COVID-19 patient by LC-MS/MS-based analysis. Tripathi G, Sharma N, Bindal V, Yadav M, Mathew B, Sharma S, Gupta E, Singh Maras J, Sarin SK. STAR Protoc. 2022 Mar 18;3(1):101045. doi: 10.1016/j.xpro.2021.101045. Epub 2021 Nov 27. PMID: 34870243 Free PMC article.
• 7. Predictors of steroid non-response and new approaches in severe alcoholic hepatitis. Sarin SK, Sharma S. Clin Mol Hepatol. 2020 Oct;26(4):639-651. doi: 10.3350/cmh.2020.0196. Epub 2020 Oct 1. PMID: 33053936 Free PMC article.
• 8. Gilbert's Syndrome in Children with Unconjugated Hyperbilirubinemia - An Analysis of 170 Cases. Sood V, Lal BB, Sharma S, Khanna R, Siloliya MK, Alam S. Indian J Pediatr. 2021 Feb;88(2):154-157. doi: 10.1007/s12098-020-03271-6. Epub 2020 Mar 27. PMID: 32221786
• 9. Extracellular vesicles from hepatitis B patients serve as reservoir of hepatitis B virus DNA. Sukriti S, Choudhary MC, Maras JS, Sharma S, Thangariyal S, Singh A, Das S, Islam M, Sharma S, Trehanpati N, Gupta E, Sarin SK. J Viral Hepat. 2019 Jan;26(1):211-214. doi: 10.1111/jvh.12995. Epub 2018 Oct 25. PMID: 30187611 No abstract available.
• 10. Differential blood transcriptome modules predict response to corticosteroid therapy in alcoholic hepatitis. Sharma S, Baweja S, Maras JS, Shasthry SM, Moreau R, Sarin SK. JHEP Rep. 2021 Mar 24;3(3):100283. doi: 10.1016/j.jhepr.2021.100283. eCollection 2021 Jun. PMID: 34095796 Free PMC article.
• 11. Multi-omics analysis of respiratory specimen characterizes baseline molecular determinants associated with SARS-CoV-2 outcome. Maras JS, Sharma S, Bhat A, Rooge S, Aggrawal R, Gupta E, Sarin SK. iScience. 2021 Aug 20;24(8):102823. doi: 10.1016/j.isci.2021.102823. Epub 2021 Jul 9. PMID: 34308298 Free PMC article.
• 12. Letter to the Editor: Biomarkers for Predicting Renal Outcomes in Decompensated Cirrhosis: Need a Closer Look! Jindal A, Sharma S. Hepatology. 2021 Nov;74(5):2915-2916. doi: 10.1002/hep.32005. Epub 2021 Jun 28. PMID: 34107074 No abstract available.
• 13. Defects in energy metabolism are associated with functional exhaustion of bone marrow mesenchymal stem cells in cirrhosis. Kumar D, Maheshwari D, Nautiyal N, Shubham S, Rooge S, Anand L, Vyas A, Kumari R, Sharma S, Bihari C, Mohanty S, Maiwall R, Kumar A, Sarin SK. Am J Stem Cells. 2022 Feb 15;11(1):12-27. eCollection 2022. PMID: 35295591 Free PMC article.
• 14. Extraction and analysis of signatures from the Gene Expression Omnibus by the crowd. Wang Z, Monteiro CD, Jagodnik KM, Fernandez NF, Gundersen GW, Rouillard AD, Jenkins SL, Feldmann AS, Hu KS, McDermott MG, Duan Q, Clark NR, Jones MR, Kou Y, Goff T, Woodland H, Amaral FMR, Szeto GL, Fuchs O, Schüssler-Fiorenza Rose SM, Sharma S, Schwartz U, Bausela XB, Szymkiewicz M, Maroulis V, Salykin A, Barra CM, Kruth CD, Bongio NJ, Mathur V, Todoric RD, Rubin UE, Malatras A, Fulp CT, Galindo JA, Motiejunaite R, Jüschke C, Dishuck PC, Lahl K, Jafari M, Aibar S, Zaravinos A, Steenhuizen LH, Allison LR, Gamallo P, de Andres Segura F, Dae Devlin T, Pérez-García V, Ma'ayan A. Nat Commun. 2016 Sep 26;7:12846. doi: 10.1038/ncomms12846. PMID: 27667448 Free PMC article.
• 15. Molecular Ellipticity of Circulating Albumin-Bilirubin Complex Associates With Mortality in Patients With Severe Alcoholic Hepatitis. Das S, Maras JS, Maiwall R, Shasthry SM, Hussain S, Sharma S, Sukriti S, Singh TP, Sarin SK. Clin Gastroenterol Hepatol. 2018 Aug;16(8):1322-1332.e4. doi: 10.1016/j.cgh.2017.11.022. Epub 2017 Nov 16. PMID: 29155355
• 16. Suboptimal Level of Bone-Forming Cells in Advanced Cirrhosis are Associated with Hepatic Osteodystrophy. Bihari C, Lal D, Thakur M, Sukriti S, Mathur D, Patil AG, Anand L, Kumar G, Sharma S, Thapar S, Rajbongshi A, Rastogi A, Kumar A, Sarin SK. Hepatol Commun. 2018 Sep 4;2(9):1095-1110. doi: 10.1002/hep4.1234. eCollection 2018 Sep. PMID: 30202823 Free PMC article.
• 17. Modification Patterns of Urinary Albumin Correlates With Serum Albumin and Outcome in Severe Alcoholic Hepatitis. Das S, Hussain MS, Maras JS, Kumar J, Shasthry SM, Nayak S, Arora V, Vijayaraghavan R, Sharma S, Maiwall R, Sarin SK. J Clin Gastroenterol. 2019 Jul;53(6):e243-e252. doi: 10.1097/ MCG.0000000000000990. PMID: 29369844
• 18. Increased Expression of RUNX1 in Liver Correlates with NASH Activity Score in Patients with Non-Alcoholic Steatohepatitis (NASH). Kaur S, Rawal P, Siddiqui H, Rohilla S, Sharma S, Tripathi DM, Baweja S, Hassan M, Vlaic S, Guthke R, Thomas M, Dayoub R, Bihari C, Sarin SK, Weiss TS. Cells. 2019 Oct 18;8(10):1277. doi: 10.3390/cells8101277. PMID: 31635436 Free PMC article.
• 19. Hyperoxidized albumin modulates neutrophils to induce oxidative stress and inflammation in severe alcoholic hepatitis. Das S, Maras JS, Hussain MS, Sharma S, David P, Sukriti S, Shasthry SM, Maiwall R, Trehanpati N, Singh TP, Sarin SK. Hepatology. 2017 Feb;65(2):631-646. doi: 10.1002/hep.28897. Epub 2016 Dec 19. PMID: 27775820
• 20. Baseline urine metabolic phenotype in patients with severe alcoholic hepatitis and its association with outcome. Maras JS, Das S, Sharma S, Shasthry SM, Colsch B, Junot C, Moreau R, Sarin SK. Hepatol Commun. 2018 Apr 16;2(6):628-643. doi: 10.1002/hep4.1176. eCollection 2018 Jun. PMID: 29881815 Free PMC article.
• 21. Adiponectin antagonizes the oncogenic actions of leptin in hepatocellular carcinogenesis. Sharma D, Wang J, Fu PP, Sharma S, Nagalingam A, Mells J, Handy J, Page AJ, Cohen C, Anania FA, Saxena NK. Hepatology. 2010 Nov;52(5):1713-22. doi: 10.1002/hep.23892. PMID: 20941777 Free PMC article.
• 22. Study of Carnitine/Acylcarnitine and Amino Acid Profile in Children and Adults With Acute Liver Failure. Sood V, Rawat D, Khanna R, Sharma S, Gupta PK, Alam S, Sarin SK. J Pediatr Gastroenterol Nutr. 2017 Jun;64(6):869-875. doi: 10.1097/ MPG.0000000000001510. PMID: 28045774
• 23. Adiponectin inhibits leptin signalling via multiple mechanisms to exert protective effects against hepatic fibrosis. Handy JA, Fu PP, Kumar P, Mells JE, Sharma S, Saxena NK, Anania FA. Biochem J. 2011 Dec 15;440(3):385-95. doi: 10.1042/BJ20102148. PMID: 21846328 Free PMC article.
• 24. Identification of Indian sub-continent as hotspot for HCV genotype 3a origin by Bayesian evolutionary reconstruction. Choudhary MC, Natarajan V, Pandey P, Gupta E, Sharma S, Tripathi R, Kumar MS, Kazim SN, Sarin SK. Infect Genet Evol. 2014 Dec;28:87-94. doi: 10.1016/j.meegid.2014.09.009. Epub 2014 Sep 16. PMID: 25224661
• 25. Dysregulated iron homeostasis is strongly associated with multiorgan failure and early mortality in acute-on-chronic liver failure. Maras JS, Maiwall R, Harsha HC, Das S, Hussain MS, Kumar C, Bihari C, Rastogi A, Kumar M, Trehanpati N, Sharma S, Pandey A, Sarin SK. Hepatology. 2015 Apr;61(4):1306-20. doi: 10.1002/hep.27636. Epub 2015 Mar 10. PMID: 25475192
• 26. Identification and full-length molecular characterization of rare hepatitis C virus genotype 5a from India. Choudhary MC, Gupta E, Pandey P, Natarajan V, Sharma S, Vashishtha C, Sharma MK, Kazim SN, Sarin SK. Arch Virol. 2015 Jan;160(1):329-33. doi: 10.1007/s00705-014-2220-2. Epub 2014 Sep 7. PMID: 25193070
• 27. Glp-1 analog, liraglutide, ameliorates hepatic steatosis and cardiac hypertrophy in C57BL/6J mice fed a Western diet. Mells JE, Fu PP, Sharma S, Olson D, Cheng L, Handy JA, Saxena NK, Sorescu D, Anania FA. Am J Physiol Gastrointest Liver Physiol. 2012 Jan 15;302(2):G225-35. doi: 10.1152/ajpgi.00274.2011. Epub 2011 Oct 28. PMID: 22038829 Free PMC article.
• 28. Downregulation of mitochondrial porin inhibits cell growth and alters respiratory phenotype in Trypanosoma brucei. Singha UK, Sharma S, Chaudhuri M. Eukaryot Cell. 2009 Sep;8(9):1418-28. doi: 10.1128/EC.00132-09. Epub 2009 Jul 17. PMID: 19617393 Free PMC article.
• 29. Pre-therapy liver transcriptome landscape in Indian and French patients with severe alcoholic hepatitis and steroid responsiveness. Sharma S, Maras JS, Das S, Hussain S, Mishra AK, Shasthry SM, Sharma CB, Weiss E, Elkrief L, Rautou PE, Gilgenkrantz H, Lotersztajn S, Paradis V, de la Grange P, Junot C, Moreau R, Sarin SK. Sci Rep. 2017 Jul 28;7(1):6816. doi: 10.1038/s41598-017-07161-4. PMID: 28754919 Free PMC article.
• 30. Cell cycle-dependent regulation of the bi-directional overlapping promoter of human BRCA2/ZAR2 genes in breast cancer cells. Misra S, Sharma S, Agarwal A, Khedkar SV, Tripathi MK, Mittal MK, Chaudhuri G. Mol Cancer. 2010 Mar 4;9:50. doi: 10.1186/1476-4598-9-50. PMID: 20202217 Free PMC article.
• 31. GLP-1 analogs reduce hepatocyte steatosis and improve survival by enhancing  the unfolded protein response and promoting macroautophagy. Sharma S, Mells JE, Fu PP, Saxena NK, Anania FA. PLoS One. 2011;6(9):e25269. doi: 10.1371/journal.pone.0025269. Epub 2011 Sep 21. PMID: 21957486 Free PMC article.
• 32. Hepatitis B Core Antibody Negativity in a Chronic Hepatitis B Infected Patient: Report of an Unusual Serological Pattern. Bajpai V, Gupta E, Kundu N, Sharma S, Shashtry SM. J Clin Diagn Res. 2017 Aug;11(8):DD04-DD06. doi: 10.7860/JCDR/2017/26821.10498. Epub 2017 Aug 1. PMID: 28969126 Free PMC article.
• 33. Bone marrow stem cells and their niche components are adversely affected in advanced cirrhosis of the liver. Bihari C, Anand L, Rooge S, Kumar D, Saxena P, Shubham S, Sukriti, Trehanpati N, Kumar G, Pamecha V, Sharma S, Rastogi A, Kumar A, Sarin SK. Hepatology. 2016 Oct;64(4):1273-88. doi: 10.1002/hep.28754. Epub 2016 Aug 24. PMID: 27486864
• 34. Genetic signatures coupled with lineage shift characterise endemic evolution of Dengue virus serotype 2 during 2015 outbreak in Delhi, India. Choudhary MC, Gupta E, Sharma S, Hasnain N, Agarwala P. Trop Med Int Health. 2017 Jul;22(7):871-880. doi: 10.1111/tmi.12898. Epub 2017 Jun 19. PMID: 28544099
• 35. Role of Tob55 on mitochondrial protein biogenesis in Trypanosoma brucei. Sharma S, Singha UK, Chaudhuri M. Mol Biochem Parasitol. 2010 Dec;174(2):89-100. doi: 10.1016/j.molbiopara.2010.07.003. Epub 2010 Jul 24. PMID: 20659504 Free PMC article.
• 36. Study of Family Clustering and PNPLA3 Gene Polymorphism in Pediatric Non Alcoholic Fatty Liver Disease. Sood V, Khanna R, Rawat D, Sharma S, Alam S, Sarin SK. Indian Pediatr. 2018 Jul 15;55(7):561-567. PMID: 30129536
• 37. Impact of family history of metabolic traits on severity of non-alcoholic steatohepatitis related cirrhosis: A cross-sectional study. Bhadoria AS, Kedarisetty CK, Bihari C, Kumar G, Jindal A, Bhardwaj A, Shasthry V, Vyas T, Benjamin J, Sharma S, Sharma MK, Sarin SK. Liver Int. 2017 Sep;37(9):1397-1404. doi: 10.1111/liv.13396. Epub 2017 Mar 24. PMID: 28231412
• 38. Inactivation of a gene for a fibronectin-binding protein of the oral bacterium Streptococcus mutans partially impairs its adherence to fibronectin. Miller-Torbert TA, Sharma S, Holt RG. Microb Pathog. 2008 Jul;45(1):53-9. doi: 10.1016/j.micpath.2008.02.001. Epub 2008 Mar 25. PMID: 18479886 Free PMC article.
• 39. Procoagulant abnormalities in cirrhosis with portal vein thrombosis. Bihari C, Saxena P, Rastogi A, Shasthry Sm, Bhadoria AS, Sharma S, Sarin SK. Indian J Gastroenterol. 2014 Sep;33(5):487-8. doi: 10.1007/s12664-014-0475-x. PMID: 24890816 No abstract available.