Bharat Bhushan, PhD

Assistant Professor of Pathology, Division of Experimental Pathology

Dr. Bhushan is a member of the Division of Experimental Pathology.

Research Interests

Our research is focused on understanding the processes of liver injury and compensatory liver regeneration during acute and chronic liver diseases. We are specifically interested in understanding the roles of receptor tyrosine kinases, MET and epidermal growth factor receptor (EGFR) in these processes. MET and EGFR are considered the most important transmembrane receptors for liver regeneration after surgical resection of liver. However, their functions are complicated by specific tissue alterations in the injured liver and remain relatively unexplored in the context of acute and chronic liver injury. Following specific projects in our laboratory are directed to understand the roles of MET and EGFR in clinically-relevant acute and chronic liver injury models with long-term goal of developing pharmacological therapies for liver diseases:

  • Firstly, we are investigating the roles of MET and EGFR in acute liver injury and compensatory liver regeneration utilizing a clinically-relevant murine model of acetaminophen (APAP) hepatotoxicity. APAP is the most commonly used over-the-counter analgesic drug across the world. APAP overdose and ensuing hepatotoxicity is the foremost cause of acute liver failure (ALF) in the US (~50% cases). Beyond the conventionally known and functionally similar role of MET and EGFR in hepatocyte proliferation, our ongoing studies show MET and EGFR play distinct roles in the pathogenesis of liver injury during ALF.
  • Secondly, we are also investigating the roles of MET and EGFR in non-alcoholic fatty liver disease (NAFLD), which has become the most common cause of chronic liver diseases worldwide, affecting 25% of world population and ~80 -100 million individuals in the US itself. Alarmingly, there is currently no approved pharmacological treatment for NAFLD. Utilizing a murine fast-food diet (FFD) model, our recent work has demonstrated a novel role of EGFR (but not MET) in regulating lipid metabolism, steatosis and chronic liver injury during NAFLD. Studies are underway to investigate the signaling mechanisms underlying this differential role of EGFR and MET in NAFLD.
Representative Publications

View Dr. Bhushan's publications on PubMed.

  • Michalopoulos GK and Bhushan B. Liver Regeneration: Biologic and Pathobiologic mechanisms and implications. Nature Reviews Gastroenterology & Hepatology. 2021 Jan; 18(1):40-55. PMID: 32764740.
  • Bhushan B, Molina L, Koral K, Stoops JW, Mars WM, Banerjee S, Orr A, Paranjpe S, Monga SP, Locker J and Michalopoulos GK. YAP is crucial for CAR-driven hepatocyte proliferation, but not for induction of drug metabolism genes in mice. Hepatology. 2020 Aug 13. PMID: 32794202.
  • Bhushan B, Gunewardena S, Edwards G and Apte U. Comparison of liver regeneration after partial hepatectomy and acetaminophen-induced acute liver failure: A global picture based on transcriptome analysis. Food and Chemical Toxicology. 2020 May; 139: 111186. PMID: 32045647.
  • Xue Y, Bhushan B, Mars WM, Bowen W, Tao J, Orr A, Stoops J, Yu Y, Luo J, Duncan A and Michalopoulos GK. pEzrin (Thr567) regulates Hippo pathway and Yap in liver. American Journal of Pathology. 2020; 190(7):1427-1437. PMID: 32289287.
  • Bhushan B and Apte U. Acetaminophen Tests Battery (ATB): a comprehensive method to study acetaminophen-induced acute liver injury. Gene Expression. 2020; 20(2):125-138. PMID: 32443984.
  • Bhushan B and Michalopoulos GK. Role of epidermal growth factor receptor in liver injury and lipid metabolism: emerging new roles for an old receptor. Chemico-Biological Interactions. 2020, 324: 109090. PMID: 32283070.
  • Bhushan B, Banerjee S, Paranjpe S, Koral K, Mars WM, Stoops JW, Orr A, Bowen WC, Locker J and Michalopoulos GK. Pharmacologic inhibition of epidermal growth factor receptor suppresses nonalcoholic fatty liver disease in murine fast-food diet model. Hepatology. 2019, 70(5): 1546-1563. PMID: 31063640.
  • Bhushan B, Stoops JW, Mars WM, Orr A, Bowen WC, Paranjpe S, and Michalopoulos GK. TCPOBOP-induced hepatomegaly and hepatocyte proliferation are attenuated by combined disruption of MET & EGFR signaling. Hepatology. 2019, 69(4): 1702-1718. PMID: 29888801.
  • Bhushan B and Apte U. Liver regeneration after acetaminophen-induced hepatotoxicity: mechanisms and therapeutic opportunities. American Journal of Pathology, 2019, 189(4): 719-729. PMID: PMID: 30653954.
  • Coudriet GM, Stoops JW, Orr A, Bhushan B, Koral K, Lee S, Previte DM, Dong HH, Michalopoulos GK, Mars WM and Piganelli JD. A noncanonical role for plasminogen activator inhibitor type 1 in obesity-induced diabetes. American Journal of Pathology. 2019. 189(7):1413-1422. PMID: 31054988.
  • Borude P, Bhushan B, Gunewardena S, Akakpo J, Jaeschke H and Apte U. Pleiotropic role of p53 in injury and liver regeneration after acetaminophen overdose. American Journal of Pathology. 2018, 188(6):1406-1418. PMID: 29654721.
  • McGreal SR, Bhushan B, Walesky C, McGill MR, Lebofsky M, Kandel SE, Winefield RD, Jaeschke H, Zachara NE, Zhang Z, Tan EP, Slawson C and Apte U. Modulation of O-GlcNAc levels in the liver impacts acetaminophen-induced liver injury by affecting protein adduct formation and glutathione synthesis. Toxicological Sciences. 2018, 162(2): 599-610. PMID: 29325178.
  • Borude P, Bhushan B and Apte U. DNA damage response regulates initiation of liver regeneration following acetaminophen overdose. Gene Expression. 2018, 18(2):115-123. PMID: 29540258.