Faculty Profile

Dr. Sanjeev Gupta, M.D.,  M.B.B.S.

Sanjeev Gupta, M.D., M.B.B.S.

Professor, Department of Medicine (Hepatology)

Professor, Department of Pathology

The Eleazar & Feige Reicher Chair in Translational Medicine, Department of Medicine

Professional Interests

Liver regeneration is critical for health. We focus on cell-based therapies and translational aspects of stem cell biology for regenerating liver. Major efforts are devoted to understanding cellular and molecular mechanisms that impair proliferation of native cells in health and disease. Mechanisms are examined by which cell transplantation may advance liver regeneration. This includes how transplanted cells may engraft, proliferate and function in liver. Cell interactions that may benefit liver regeneration are of interest. The therapeutic potential of liver cell types is also of interest. We define molecular aspects of hepatic differentiation in human stem/progenitor cells isolated from tissues or hepatocytes generated by differentiation of pluripotent stem cells. Comparative analysis of such cells is of interest for mechanisms in gene regulation. Expression of therapeutic constructs and transplantation of those cells is another area of investigative interest. In other projects, we determine whether endogenous stem/progenitor cells may be activated by cell therapy approaches. This concerns identification of specific paracrine factors released by transplanted cells. This interfaces with opportunities for candidate drug development for modulating receptors with cytoprotective potential. Intracellular signaling pathways and mechanisms related to DNA damage and repair, as well as mitochondrial biology have become relevant. Diseases of therapeutic interest include acute liver failure (mechanisms for liver regeneration), genetic deficiency states (Wilson's disease with hepatic copper toxicosis for cell/gene therapy approaches), and coagulopathies (disease correction with cell therapy). Tissue engineering to generate neo-liver has potential in these areas and is studied in experimental models.

Microarray or deep sequencing-based methods are routinely applied for gene expression. Established cell and molecular biology methods are broadly used. Several rodent models are used, including hemophilia A mouse, Gunn rat, Nagase analbuminemic rat, dipeptidyl peptidase IV deficient (DPPIV-) rat and DPPIV- mouse, Long-Evans Cinnamon rat, etc. Animal models with induced acute or chronic liver injury are available. The DPPIV- rat and mouse-based transplantation systems have been helpful for fate of transplanted cells. Cell culture assays are used for mechanistic analyses. Studies are also devoted to major issues in transplantation, e.g., cryopreservation, organ donor expansions through study of nonheart-beating donors. Clinically used drugs are used to advance translation.

We collaborate with leading investigators at Einstein or elsewhere as indicated.

Selected Publications

  • Sharma Y, Liu J, Kristian KE, Follenzi A, Gupta S. In Atp7b-/- mice modeling Wilson's disease liver repopulation with bone marrow-derived myofibroblasts or inflammatory cells and not hepatocytes is delterious. Gene Expr. 2018 Jul 20. doi: 10.3727/105221618X15320123457380. [Epub ahead of print]. PMID: 30029699
  • Bandi S, Gupta S, Tchaikovskaya T, Gupta S. Differentiation in stem/progenitor cells along fetal or adult hepatic stages requires transcriptional regulators independently of oscillations in microRNA expression. Exp Cell Res. 2018 Sep 1;370(1):1-12. doi: 10.1016/j.yexcr.2018.06.004. Epub 2018 Jun 6.
  • Benten D, Kluwe J, Wirth JW, Thiele ND, Follenzi A, Bhargava KK, Palestro CJ, Koepke M, Tjandra R, Volz T, Lutgehetmann M, Gupta S. A humanized mouse model with liver fibrosis following expansion of transplanted hepatic stellate cells in injury and inflammation. Lab Invest 2018 Apr;98(4):525-536. doi: 10.1038/s41374-017-0010-7. Epub 2018 Jan 19.PMID: 29352225.
  • Viswanathan P, Sharma Y, Gupta P, Gupta S. Replicative stress and alterations in cell cycle checkpoint controls following acetaminophen hepatotoxicity restrict hepatic regeneration. Cell Prolif 2018; Jun;51(3):e12445. doi: 10.1111/cpr.12445. Epub 2018 Mar 5. PMID: 29504225.
  • Kakabadze Z, Kakabadze A, Chakhunashvili D, Karalashvili L, Berishvili E, Sharma Y, Gupta S. Decellularized human placenta supports hepatic tissue and allows rescue in acute liver failure. Hepatology 2018 May;67(5):1956-1969. PMID: 29211918. 
  • Rogler CE, Bebawee R, Matarlo J, Locker J, Pattamanuch N, Gupta S, Rogler LE. Triple staining including FOXA2 identifies stem cell lineages undergoing hepatic and biliary differentiation in cirrhotic human liver. J Histochem Cytochem 2017 Jan;65(1):33-46. doi: 10.1369/0022155416675153. Epub 2016 Nov 24. PMID: 27879410.
  • Viswanathan P, Gupta P, Kapoor S, Gupta S. Thalidomide promotes transplanted cell engraftment in the rat liver by modulating inflammation and endothelial integrity. J Hepatol 2016 Jul 12. pii: S0168-8278(16)30332-4. doi: 10.1016/j.jhep.2016.07.008. [Epub ahead of print]
  • Merlin S, Bhargava K, Ranaldo G, Zanolini D, Palestro C, Santambrogio L, Prat M, Follenzi A, Gupta S. Kupffer cell transplantation in mice for elucidating monocyte/macrophage biology and for potential in cell or gene therapy. Am J Pathol 2016 Mar;186(3):539-51. doi: 10.1016/j.ajpath.2015.11.002. Epub 2016 Jan 7. 015 Apr 24.
  • Kumar M, Sharma Y, Bandi S, Gupta S. Endogenous antiviral microRNAs determine permissiveness for hepatitis B virus replication in cultured human fetal and adult hepatocytes. J Med Virol 2015 Jul;87(7):1168-83. doi: 10.1002/jmv.24145. Epub 2015 Feb 17. 

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Research Information

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