Neil Kaplowitz, MD

Dr. Kaplowitz’s research interests include drug toxicity, signal transduction, oxidative stress, glutathione metabolism, pathogenesis of alcoholic liver disease, endoplasmic reticulum (ER) stress, and mitochondrial biogenesis.

Dr. Kaplowitz earned his medical degree from New York University School of Medicine. He then went on to complete a Gastroenterology Fellowship at Cornell University Medical College.

• Western Gastroenterology: Research Prize, 1986
• Association of American Physicians: Member, 1988
• NIH: Merit Award, 1992
• Department of Veterans Affairs: William S. Middleton Award, 1993
• New York University School of Medicine: Solomon A. Berson Medical Alumni Achievement Award in Clinical Science, 1994
• American Liver Foundation: Greater Los Angeles Medical Honoree, 2000
• American Gastroenterological Association: Foundation Research Mentor Award Honoree, 2005
• Wadworth VA Alumni Association: William H. Oldendorf Lifetime Achievement Award, 2006
• American Association for the Study of Liver Diseases: Distinguished Achievement Award, 2006
• Western Society of Clinical Investigation: Mayo Soley Award, 2007
• American Liver Foundation: Distinguished Scientific Achievement Award, 2008

• Targets of JNK in acute hepatotoxicity.
  NIH · R01DK126866 · Sep 18, 2020 – May 31, 2025 · Role: Principal Investigator
• Retrograde Signaling in Alcohol-Induced Mitochondrial Stress and Biogenesis.
  NIH · R21AA017746 · Sep 15, 2008 – Aug 31, 2010 · Role: Principal Investigator
• Cellular Mechanisms of Hepatotoxicity.
  NIH · R01DK067215 · Apr 1, 2004 – Feb 28, 2021 · Role: Principal Investigator
• Homocysteine, ER Stress and Alcoholic Liver Injury.
  NIH · R01AA014428 · Jul 1, 2003 – Mar 31, 2015 · Role: Principal Investigator
• USC Research Center for Liver Disease
  NIH · P30DK048522 · Mar 1, 1995 – Feb 28, 2021 · Role: Principal Investigator
• EFFECT OF ETHANOL ON HEPATIC GSH HOMEOSTASIS
  NIH · R01AA009526 · Apr 1, 1993 – Mar 31, 2001 · Role: Principal Investigator
• ROLE OF CYTOKINE INFLAMMATION
  NIH · R13DK044465 · Sep 30, 1991 – Aug 31, 1992 · Role: Principal Investigator
• PHYSIOLOGY OF GLUTATHIONE EFFLUX FROM THE LIVER
  NIH · R01DK030312 · Feb 1, 1982 – May 31, 2005 · Role: Principal Investigator
• PHYSIOLOGY OF GLUTATHIONE EFFLUX FROM THE LIVER
  NIH · R37DK030312 · Feb 1, 1982 – May 31, 2000 · Role: Principal Investigator
• THE PHYSIOLOGY OF GLUTATHIONE EFFLUX FROM THE LIVER
  NIH · R01AM030312 · Feb 1, 1982 – Jan 31, 1987 · Role: Principal Investigator

• Models of acute and chronic liver disease

• NIH Awards $6 Million for Liver Research (04/30/2010)

• Bile acids in liver and gastrointestinal cancer. Semin Cancer Biol. 2025 11; 116:45-58.. View in PubMed
• Early oxidative protein modifications and gut damage/leakiness contribute to drug-induced acute liver failure. Clin Mol Hepatol. 2026 Jan; 32(1):e29-e33.. View in PubMed
• Hepatic LRP-1 plays an important role in amyloidosis in Alzheimer’s disease mice: Potential role in chronic heavy alcohol feeding. Neurobiol Dis. 2024 09; 199:106570.. View in PubMed
• Mitochondrial P-JNK target, SAB (SH3BP5), in regulation of cell death. Front Cell Dev Biol. 2024; 12:1359152.. View in PubMed
• Oral magnesium prevents acetaminophen-induced acute liver injury by modulating microbial metabolism. Cell Host Microbe. 2024 01 10; 32(1):48-62.e9.. View in PubMed
• Clinical presentation, causative drugs and outcome of patients with autoimmune features in two prospective DILI registries. Liver Int. 2023 08; 43(8):1749-1760.. View in PubMed
• c-Jun-N Terminal Kinase-Mediated Degradation of γ-Glutamylcysteine Ligase Catalytic Subunit Inhibits GSH Recovery After Acetaminophen Treatment: Role in Sustaining JNK Activation and Liver Injury. Antioxid Redox Signal. 2023 06; 38(16-18):1071-1081.. View in PubMed
• Modulation of hepatic amyloid precursor protein and lipoprotein receptor-related protein 1 by chronic alcohol intake: Potential link between liver steatosis and amyloid-β. Front Physiol. 2022; 13:930402.. View in PubMed
• Endoplasmic reticulum stress in liver diseases. Hepatology. 2023 02 01; 77(2):619-639.. View in PubMed
• Introducing Laurie DeLeve, M.D., Ph.D., Our 2022 AASLD President. Hepatology. 2022 03; 75(3):514-517.. View in PubMed
• Hepatic Mitochondrial SAB Deletion or Knockdown Alleviates Diet-Induced Metabolic Syndrome, Steatohepatitis, and Hepatic Fibrosis. Hepatology. 2021 12; 74(6):3127-3145.. View in PubMed
• Key Characteristics of Human Hepatotoxicants as a Basis for Identification and Characterization of the Causes of Liver Toxicity. Hepatology. 2021 12; 74(6):3486-3496.. View in PubMed
• The gut microbial metabolite, 3,4-dihydroxyphenylpropionic acid, alleviates hepatic ischemia/reperfusion injury via mitigation of macrophage pro-inflammatory activity in mice. Acta Pharm Sin B. 2022 Jan; 12(1):182-196.. View in PubMed
• Alcohol, Fasting, and Therapeutic Dosing of Acetaminophen: A Perfect Storm. Hepatology. 2021 05; 73(5):1634-1636.. View in PubMed
• Comprehensive analysis and insights gained from long-term experience of the Spanish DILI Registry. J Hepatol. 2021 07; 75(1):86-97.. View in PubMed
• Clinical Characteristics and Outcome of Drug-Induced Liver Injury in the Older Patients: From the Young-Old to the Oldest-Old. Clin Pharmacol Ther. 2021 04; 109(4):1147-1158.. View in PubMed
• REPLY. Hepatol Commun. 2020 Nov; 4(11):1725.. View in PubMed
• Markedly Elevated Serum Aspartate Aminotransferase to Alanine Aminotransferase Ratio: A Clue to Hepatic Neoplasia. Hepatol Commun. 2020 Jul; 4(7):1099-1101.. View in PubMed
• Acetaminophen Hepatotoxicity: Strong Offense and Weakened Defense. Hepatology. 2020 05; 71(5):1530-1532.. View in PubMed
• Gut Microbiota and Liver Injury (I)-Acute Liver Injury. Adv Exp Med Biol. 2020; 1238:23-37.. View in PubMed
• Expression of mitochondrial membrane-linked SAB determines severity of sex-dependent acute liver injury. J Clin Invest. 2019 12 02; 129(12):5278-5293.. View in PubMed
• IgG:IgM Ratios of Liver Plasma Cells Reveal Similar Phenotypes of Primary Biliary Cholangitis With and Without Features of Autoimmune Hepatitis. Clin Gastroenterol Hepatol. 2021 02; 19(2):397-399.. View in PubMed
• Intestinal Epithelial Chemokine (C-C Motif) Ligand 7 Overexpression Enhances Acetaminophen-Induced Hepatotoxicity in Mice. Am J Pathol. 2020 01; 190(1):57-67.. View in PubMed
• Drug-induced liver injury. Nat Rev Dis Primers. 2019 08 22; 5(1):58.. View in PubMed
• Endoplasmic Reticulum Stress-Induced Upregulation of STARD1 Promotes Acetaminophen-Induced Acute Liver Failure. Gastroenterology. 2019 08; 157(2):552-568.. View in PubMed
• The Regulation of JNK Signaling Pathways in Cell Death through the Interplay with Mitochondrial SAB and Upstream Post-Translational Effects. Int J Mol Sci. 2018 Nov 20; 19(11).. View in PubMed
• Niacin-Induced Anicteric Microvesicular Steatotic Acute Liver Failure. Hepatol Commun. 2018 Nov; 2(11):1293-1298.. View in PubMed
• Glycycoumarin protects mice against acetaminophen-induced liver injury predominantly via activating sustained autophagy. Br J Pharmacol. 2018 10; 175(19):3747-3757.. View in PubMed
• Herb-Induced Liver Injury: A Global Concern. Chin J Integr Med. 2018 Sep; 24(9):643-644.. View in PubMed
• New insights into the role and mechanism of c-Jun-N-terminal kinase signaling in the pathobiology of liver diseases. Hepatology. 2018 05; 67(5):2013-2024.. View in PubMed
• Gut microbiota mediates diurnal variation of acetaminophen induced acute liver injury in mice. J Hepatol. 2018 07; 69(1):51-59.. View in PubMed
• Prediction of histologic alcoholic hepatitis based on clinical presentation limits the need for liver biopsy. Hepatol Commun. 2017 12; 1(10):1070-1084.. View in PubMed
• Heparan sulfate promotes recovery from acute liver injury: Inhibition of progressive cell death or enhanced regeneration? Hepatology. 2017 11; 66(5):1381-1383. Apte U, Kaplowitz N . . View in PubMed
• The 2-oxoglutarate carrier promotes liver cancer by sustaining mitochondrial GSH despite cholesterol loading. Redox Biol. 2018 04; 14:164-177.. View in PubMed
• Death and liver transplantation within 2 years of onset of drug-induced liver injury. Hepatology. 2017 10; 66(4):1275-1285.. View in PubMed
• The role of MAP2 kinases and p38 kinase in acute murine liver injury models. Cell Death Dis. 2017 06 29; 8(6):e2903.. View in PubMed
• Drug-Induced Liver Injury: Cascade of Events Leading to Cell Death, Apoptosis or Necrosis. Int J Mol Sci. 2017 May 09; 18(5).. View in PubMed
• Hepatic FcRn regulates albumin homeostasis and susceptibility to liver injury. Proc Natl Acad Sci U S A. 2017 04 04; 114(14):E2862-E2871.. View in PubMed
• Protective role of p53 in acetaminophen hepatotoxicity. Free Radic Biol Med. 2017 05; 106:111-117.. View in PubMed
• Competing Mechanistic Hypotheses of Acetaminophen-Induced Hepatotoxicity Challenged by Virtual Experiments. PLoS Comput Biol. 2016 12; 12(12):e1005253.. View in PubMed
• Questions and controversies: the role of necroptosis in liver disease. Cell Death Discov. 2016; 2:16089.. View in PubMed
• Mitochondrial remodeling in the liver following chronic alcohol feeding to rats. Free Radic Biol Med. 2017 01; 102:100-110.. View in PubMed
• A murder mystery in the liver: who done it and how? J Clin Invest. 2016 11 01; 126(11):4068-4071. Dara L , Liu ZX, Kaplowitz N . . View in PubMed
• Antcin H Protects Against Acute Liver Injury Through Disruption of the Interaction of c-Jun-N-Terminal Kinase with Mitochondria. Antioxid Redox Signal. 2017 02 10; 26(5):207-220.. View in PubMed
• Knockdown of RIPK1 Markedly Exacerbates Murine Immune-Mediated Liver Injury through Massive Apoptosis of Hepatocytes, Independent of Necroptosis and Inhibition of NF-κB. J Immunol. 2016 10 15; 197(8):3120-3129.. View in PubMed
• The many faces of RIPK3: What about NASH? Hepatology. 2016 11; 64(5):1411-1413. Dara L , Kaplowitz N . . View in PubMed
• Definition and risk factors for chronicity following acute idiosyncratic drug-induced liver injury. J Hepatol. 2016 09; 65(3):532-42.. View in PubMed
• c-Jun N-terminal kinase mediates mouse liver injury through a novel Sab (SH3BP5)-dependent pathway leading to inactivation of intramitochondrial Src. Hepatology. 2016 06; 63(6):1987-2003.. View in PubMed
• Reply. Hepatology. 2016 07; 64(1):312-3.. View in PubMed
• Alcoholic foamy degeneration and alcoholic fatty liver with jaundice: Often overlooked causes of jaundice and hepatic decompensation that can mimic alcoholic hepatitis. Clin Liver Dis (Hoboken). 2015 Dec; 6(6):145-148.. View in PubMed
• Lysosomal Cholesterol Accumulation Sensitizes To Acetaminophen Hepatotoxicity by Impairing Mitophagy. Sci Rep. 2015 Dec 11; 5:18017.. View in PubMed
• Mechanisms of adaptation and progression in idiosyncratic drug induced liver injury, clinical implications. Liver Int. 2016 Feb; 36(2):158-65.. View in PubMed
• HLA-B*57:01 Confers Susceptibility to Pazopanib-Associated Liver Injury in Patients with Cancer. Clin Cancer Res. 2016 Mar 15; 22(6):1371-7.. View in PubMed
• Clinical Pattern of Tolvaptan-Associated Liver Injury in Subjects with Autosomal Dominant Polycystic Kidney Disease: Analysis of Clinical Trials Database. Drug Saf. 2015 Nov; 38(11):1103-13.. View in PubMed
• Reply. Hepatology. 2016 07; 64(1):308-9.. View in PubMed
• Is Sensitivity the Key Measure to Predict Acute Liver Failure in Drug-Induced Liver Injury Patients? Clin Gastroenterol Hepatol. 2016 06; 14(6):918. Robles-Diaz M, Andrade RJ, Kaplowitz N . View in PubMed
• Receptor interacting protein kinase 1 mediates murine acetaminophen toxicity independent of the necrosome and not through necroptosis. Hepatology. 2015 Dec; 62(6):1847-57.. View in PubMed
• Inhibition of immune tolerance unmasks drug-induced allergic hepatitis. Hepatology. 2015 Aug; 62(2):346-8.. View in PubMed
• Characterisation of liver chemistry abnormalities associated with pazopanib monotherapy: a systematic review and meta-analysis of clinical trials in advanced cancer patients. Eur J Cancer. 2015 Jul; 51(10):1293-302.. View in PubMed
• Targeting signal transduction pathways which regulate necrosis in acetaminophen hepatotoxicity. J Hepatol. 2015 Jul; 63(1):5-7.. View in PubMed
• Sab (Sh3bp5) dependence of JNK mediated inhibition of mitochondrial respiration in palmitic acid induced hepatocyte lipotoxicity. J Hepatol. 2015 Jun; 62(6):1367-74.. View in PubMed
• Reply: To Gastroenterology. 2015 Feb; 148(2):452-3. Robles-Diaz M, Kaplowitz N , Stephens C, Andrade RJ, Lucena MI . View in PubMed
• The clinical liver safety assessment best practices workshop: rationale, goals, accomplishments and the future. Drug Saf. 2014 Nov; 37.. View in PubMed
• Liver safety assessment in special populations (hepatitis B, C, and oncology trials). Drug Saf. 2014 Nov; 37.. View in PubMed
• Reply: To Gastroenterology. 2014 Dec; 147(6):1442. Robles-Diaz M, Kaplowitz N , Stephens C, Andrade RJ, Lucena MI . View in PubMed
• Acid sphingomyelinase-ceramide system in steatohepatitis: a novel target regulating multiple pathways. J Hepatol. 2015 Jan; 62(1):219-33.. View in PubMed
• In vitro assays of mitochondrial function/dysfunction. Clin Pharmacol Ther. 2014 Dec; 96(6):665-8.. View in PubMed
• Cell death and cell death responses in liver disease: mechanisms and clinical relevance. Gastroenterology. 2014 Oct; 147(4):765-783.e4.. View in PubMed
• ASMase regulates autophagy and lysosomal membrane permeabilization and its inhibition prevents early stage non-alcoholic steatohepatitis. J Hepatol. 2014 Nov; 61(5):1126-34.. View in PubMed
• Respiratory substrates regulate S-nitrosylation of mitochondrial proteins through a thiol-dependent pathway. Chem Res Toxicol. 2014 May 19; 27(5):794-804.. View in PubMed
• Use of Hy’s law and a new composite algorithm to predict acute liver failure in patients with drug-induced liver injury. Gastroenterology. 2014 Jul; 147(1):109-118.e5.. View in PubMed
• Protein kinase C (PKC) participates in acetaminophen hepatotoxicity through c-jun-N-terminal kinase (JNK)-dependent and -independent signaling pathways. Hepatology. 2014 Apr; 59(4):1543-1554.. View in PubMed
• JNK interaction with Sab mediates ER stress induced inhibition of mitochondrial respiration and cell death. Cell Death Dis. 2014 Jan 09; 5:e989.. View in PubMed
• Role of Mitochondria in Alcoholic Liver Disease. Curr Pathobiol Rep. 2013 Sep 01; 1(3):159-168.. View in PubMed
• Mechanisms of drug-induced liver injury. Clin Liver Dis. 2013 Nov; 17(4):507-18.. View in PubMed
• Avoiding idiosyncratic DILI: two is better than one. Hepatology. 2013 Jul; 58(1):15-7.. View in PubMed
• ASMase is required for chronic alcohol induced hepatic endoplasmic reticulum stress and mitochondrial cholesterol loading. J Hepatol. 2013 Oct; 59(4):805-13.. View in PubMed
• Regulation of drug-induced liver injury by signal transduction pathways: critical role of mitochondria. Trends Pharmacol Sci. 2013 Apr; 34(4):243-53.. View in PubMed
• Current challenges and controversies in drug-induced liver injury. Drug Saf. 2012 Dec 01; 35(12):1099-117.. View in PubMed
• Mitochondrial glutathione: features, regulation and role in disease. Biochim Biophys Acta. 2013 May; 1830(5):3317-28.. View in PubMed
• Dynamic adaptation of liver mitochondria to chronic alcohol feeding in mice: biogenesis, remodeling, and functional alterations. J Biol Chem. 2012 Dec 07; 287(50):42165-79.. View in PubMed
• Mitochondrial GSH determines the toxic or therapeutic potential of superoxide scavenging in steatohepatitis. J Hepatol. 2012 Oct; 57(4):852-9.. View in PubMed
• Interstrain differences in liver injury and one-carbon metabolism in alcohol-fed mice. Hepatology. 2012 Jul; 56(1):130-9.. View in PubMed
• Investigation of chronic alcohol consumption in rodents via ultra-high-performance liquid chromatography-mass spectrometry based metabolite profiling. J Chromatogr A. 2012 Oct 12; 1259:128-37.. View in PubMed
• Dealing with stress. Hepatology. 2012 Jan; 55(1):3-13.. View in PubMed
• c-Jun N-terminal kinase (JNK)-dependent acute liver injury from acetaminophen or tumor necrosis factor (TNF) requires mitochondrial Sab protein expression in mice. J Biol Chem. 2011 Oct 07; 286(40):35071-8.. View in PubMed
• Genetic variation in UGT1A1 typical of Gilbert syndrome is associated with unconjugated hyperbilirubinemia in patients receiving tocilizumab. Pharmacogenet Genomics. 2011 Jul; 21(7):365-74.. View in PubMed
• Liver-specific loss of glucose-regulated protein 78 perturbs the unfolded protein response and exacerbates a spectrum of liver diseases in mice. Hepatology. 2011 Jul; 54(1):229-39.. View in PubMed
• Case definition and phenotype standardization in drug-induced liver injury. Clin Pharmacol Ther. 2011 Jun; 89(6):806-15.. View in PubMed
• Role of cAMP-responsive element-binding protein (CREB)-regulated transcription coactivator 3 (CRTC3) in the initiation of mitochondrial biogenesis and stress response in liver cells. J Biol Chem. 2011 Jun 24; 286(25):22047-54.. View in PubMed
• The contribution of endoplasmic reticulum stress to liver diseases. Hepatology. 2011 May; 53(5):1752-63.. View in PubMed
• Differential effect of gender on hepatic fat. Pediatr Radiol. 2011 Sep; 41(9):1146-53.. View in PubMed
• Recurrent drug-induced liver injury (DILI) with different drugs in the Spanish Registry: the dilemma of the relationship to autoimmune hepatitis. J Hepatol. 2011 Oct; 55(4):820-7.. View in PubMed
• Metabonomic investigation of liver profiles of nonpolar metabolites obtained from alcohol-dosed rats and mice using high mass accuracy MSn analysis. J Proteome Res. 2011 Feb 04; 10(2):705-13.. View in PubMed
• Regulation of mitochondrial glutathione redox status and protein glutathionylation by respiratory substrates. J Biol Chem. 2010 Dec 17; 285(51):39646-54.. View in PubMed
• Mechanisms of pathogenesis in drug hepatotoxicity putting the stress on mitochondria. Mol Interv. 2010 Apr; 10(2):98-111.. View in PubMed
• Differences in betaine-homocysteine methyltransferase expression, endoplasmic reticulum stress response, and liver injury between alcohol-fed mice and rats. Hepatology. 2010 Mar; 51(3):796-805.. View in PubMed
• Silencing glycogen synthase kinase-3beta inhibits acetaminophen hepatotoxicity and attenuates JNK activation and loss of glutamate cysteine ligase and myeloid cell leukemia sequence 1. J Biol Chem. 2010 Mar 12; 285(11):8244-55.. View in PubMed
• Signal transduction pathways involved in drug-induced liver injury. Handb Exp Pharmacol. 2010.. View in PubMed
• Diagnosis, management and prevention of drug-induced liver injury. Gut. 2009 Nov; 58(11):1555-64.. View in PubMed

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