Professor
Department of Medicine - Gastroenterology
Primary Thematic Area
Secondary Thematic Area
Research Summary
NAFLD disease modeling using patient-derived iPSCs
Our laboratory studies basic biological processes relevant to liver biology and disease. Our main focus is on nonalcoholic fatty liver disease (NAFLD), which affects 25% of the world’s population. We have extensive experience modeling NAFLD in mouse models, but have recently redirected our research to concentrate on characterization of NAFLD disease signatures in human liver cells differentiated from iPSCs. We conduct studies on iPSC-derived liver cells from a large cohort of NAFLD and control patients, who harbor a variety of genetic variants associated with NAFLD. Our goal is to determine how genetic variants, alone and in combination, contribute to NAFLD disease phenotypes in iPSC-derived liver cell culture systems.
Websites
Publications
Loss of function of T-box 3 in the liver protects against MASLD.
The Journal of clinical investigation
iPSC-Derived Hepatocytes from Patients with MASLD Exhibit Early Mitochondrial Dysfunction.
bioRxiv : the preprint server for biology
Exploring the impact of graded alcohol use on atherogenic lipid profiles among Latinos with underlying chronic liver disease.
Alcohol, clinical & experimental research
AAV capsid prioritization in normal and steatotic human livers maintained by machine perfusion.
Nature biotechnology
Pervasive and programmed nucleosome distortion patterns on single mammalian chromatin fibers.
bioRxiv : the preprint server for biology
Predicting Metabolic Dysfunction Associated Steatotic Liver Disease Risk Using Patient-Derived Induced Pluripotent Stem Cells.
bioRxiv : the preprint server for biology
Novel autoantibody targets identified in patients with autoimmune hepatitis (AIH) by PhIP-Seq reveals pathogenic insights.
medRxiv : the preprint server for health sciences
Hyperpolarized [1-13 C] pyruvate MRSI to detect metabolic changes in liver in a methionine and choline-deficient diet rat model of fatty liver disease.
Magnetic resonance in medicine
A genetic basis of mitochondrial DNAJA3 in nonalcoholic steatohepatitis-related hepatocellular carcinoma.
Hepatology (Baltimore, Md.)
Modeling and therapeutic targeting of inflammation-induced hepatic insulin resistance using human iPSC-derived hepatocytes and macrophages.
Nature communications
Doxycycline Significantly Enhances Induction of iPSCs to Endoderm by Enhancing survival via AKT Phosphorylation.
Hepatology (Baltimore, Md.)
Visceral Adipose Tissue Inflammation and Radiographic Visceral-to-Subcutaneous Adipose Tissue Ratio in Patients with Cirrhosis.
Digestive diseases and sciences
iPSC-derived hepatocytes from patients with nonalcoholic fatty liver disease display a disease-specific gene expression profile.
Gastroenterology
Hepatocyte-specific deletion of XBP1 sensitizes mice to liver injury through hyperactivation of IRE1α.
Cell death and differentiation
Ly6cLo non-classical monocytes promote resolution of rhesus rotavirus-mediated perinatal hepatic inflammation.
Scientific reports
Nonalcoholic Fatty Liver Disease in 2020.
Gastroenterology
Macronutrients and the adipose-liver axis in obesity and fatty liver.
Cellular and molecular gastroenterology and hepatology
Loss of integrin avß8 in murine hepatocytes accelerates liver regeneration.
The American journal of pathology
Macrophages Steal STING From the Infectious Disease Playbook to Promote Nonalcoholic Fatty Liver Disease.
Gastroenterology
Race/ethnicity is an independent risk factor for autoimmune hepatitis among the San Francisco underserved.
Autoimmunity
Hospitalizations for Autoimmune Hepatitis Disproportionately Affect Black and Latino Americans.
The American journal of gastroenterology
Specific Macronutrients Exert Unique Influences on the Adipose-Liver Axis to Promote Hepatic Steatosis in Mice.
Cellular and molecular gastroenterology and hepatology
Modeling fatty liver disease in animals: Is there an optimal approach, and is the effort worthwhile?
Hepatology (Baltimore, Md.)
Nonalcoholic fatty liver disease.
Nature reviews. Disease primers
Isocaloric manipulation of macronutrients within a high-carbohydrate/moderate-fat diet induces unique effects on hepatic lipogenesis, steatosis and liver injury.
The Journal of nutritional biochemistry
Differential hepatotoxicity of dietary and DNL-derived palmitate in the methionine-choline-deficient model of steatohepatitis.
BMC gastroenterology
A screen in mice uncovers repression of lipoprotein lipase by microRNA-29a as a mechanism for lipid distribution away from the liver.
Hepatology (Baltimore, Md.)
Mechanisms of Liver Injury in Non-Alcoholic Steatohepatitis.
Current hepatology reports
Targeting of av integrin identifies a core molecular pathway that regulates fibrosis in several organs.
Nature medicine
A liver Hif-2a-Irs2 pathway sensitizes hepatic insulin signaling and is modulated by Vegf inhibition.
Nature medicine
Retinol binding protein 4 and fatty liver: A direct link?
Hepatology (Baltimore, Md.)
Insulin sensitivity and variability in hepatitis C virus infection using direct measurement.
Digestive diseases and sciences
The basic helix-loop-helix transcription factor, heart and neural crest derivatives expressed transcript 2, marks hepatic stellate cells in zebrafish: analysis of stellate cell entry into the developing liver.
Hepatology (Baltimore, Md.)
Specific bile acids inhibit hepatic fatty acid uptake in mice.
Hepatology (Baltimore, Md.)
Assessment of factors associated with pre-diabetes in HCV infection including direct and dynamic measurements of insulin action.
Journal of viral hepatitis
Lipids in liver disease: looking beyond steatosis.
Gastroenterology
New insights from rodent models of fatty liver disease.
Antioxidants & redox signaling
Stress signaling in the methionine-choline-deficient model of murine fatty liver disease.
Gastroenterology
Comparison of surrogate and direct measurement of insulin resistance in chronic hepatitis C virus infection: impact of obesity and ethnicity.
Hepatology (Baltimore, Md.)
Computational experiments reveal plausible mechanisms for changing patterns of hepatic zonation of xenobiotic clearance and hepatotoxicity.
Journal of theoretical biology
Dietary fructose exacerbates hepatocellular injury when incorporated into a methionine-choline-deficient diet.
Liver international : official journal of the International Association for the Study of the Liver
Trunk fat as a determinant of liver disease.
Gastroenterology
Short passive cooling protects rats during hepatectomy by inducing heat shock proteins and limiting the induction of pro-inflammatory cytokines.
The Journal of surgical research
Dietary sucrose is essential to the development of liver injury in the methionine-choline-deficient model of steatohepatitis.
Journal of lipid research
DAMPs ramp up drug toxicity.
The Journal of clinical investigation
Beyond insulin resistance: Innate immunity in nonalcoholic steatohepatitis.
Hepatology (Baltimore, Md.)
Impaired dexamethasone-mediated induction of tryptophan 2,3-dioxygenase in heme-deficient rat hepatocytes: translational control by a hepatic eIF2alpha kinase, the heme-regulated inhibitor.
The Journal of pharmacology and experimental therapeutics
Polyunsaturated fat in the methionine-choline-deficient diet influences hepatic inflammation but not hepatocellular injury.
Journal of lipid research
Alcoholic steatohepatitis: management and prognosis.
Current gastroenterology reports
Mice fed a lipogenic methionine-choline-deficient diet develop hypermetabolism coincident with hepatic suppression of SCD-1.
Journal of lipid research
VEGF modulates erythropoiesis through regulation of adult hepatic erythropoietin synthesis.
Nature medicine
ANIT toxicity toward mouse hepatocytes in vivo is mediated primarily by neutrophils via CD18.
American journal of physiology. Gastrointestinal and liver physiology
Warm ischemia-induced alterations in oxidative and inflammatory proteins in hepatic Kupffer cells in rats.
Molecular & cellular proteomics : MCP
Metabolic profiling of livers and blood from obese Zucker rats.
Journal of hepatology
Transgenic overexpression of interleukin-8 in mouse liver protects against galactosamine/endotoxin toxicity.
Journal of hepatology
Heme-reversible impairment of CYP2B1/2 induction in heme-depleted rat hepatocytes in primary culture: translational control by a hepatic alpha-subunit of the eukaryotic initiation factor kinase?
The Journal of pharmacology and experimental therapeutics
Limited role for CXC chemokines in the pathogenesis of alpha-naphthylisothiocyanate-induced liver injury.
American journal of physiology. Gastrointestinal and liver physiology
What doesn't kill you makes you stronger: how hepatocytes survive prolonged cholestasis.
Hepatology (Baltimore, Md.)
Infiltrating neutrophils in bile duct-ligated livers do not promote hepatic fibrosis.
Hepatology research : the official journal of the Japan Society of Hepatology
Treatment of alcoholic hepatitis.
Journal of gastroenterology and hepatology
Alcoholic steatosis and steatohepatitis.
Seminars in gastrointestinal disease
Blocking the secretion of hepatic very low density lipoproteins renders the liver more susceptible to toxin-induced injury.
The Journal of biological chemistry
Anti-Fas induces hepatic chemokines and promotes inflammation by an NF-kappa B-independent, caspase-3-dependent pathway.
The Journal of biological chemistry
Interactions between hepatic stellate cells and the immune system.
Seminars in liver disease
Cholesterol esterification by host and parasite is essential for optimal proliferation of Toxoplasma gondii.
The Journal of biological chemistry
Activation of the Met receptor by cell attachment induces and sustains hepatocellular carcinomas in transgenic mice.
The Journal of cell biology
Antidiabetic treatment for NASH?
Hepatology (Baltimore, Md.)
The CYP2E1 knockout delivers another punch: first ASH, now NASH. Alcoholic steatohepatitis. Nonalcoholic steatohepatitis.
Hepatology (Baltimore, Md.)
Bile duct ligation in rats induces biliary expression of cytokine-induced neutrophil chemoattractant.
Gastroenterology
Leukocytes as modulators of stellate cell activation.
Alcoholism, clinical and experimental research
Cytokines: overview.
Seminars in liver disease
How does estrogen enhance endotoxin toxicity? Let me count the ways.
Hepatology (Baltimore, Md.)
Rat hepatic stellate cells produce cytokine-induced neutrophil chemoattractant in culture and in vivo.
The American journal of physiology
Manipulation of glutathione stores in rat hepatic stellate cells does not alter collagen synthesis.
Hepatology (Baltimore, Md.)
Glutathione regulation in rat hepatic stellate cells. Comparative studies in primary culture and in liver injury in vivo.
Biochemical pharmacology
Adenovirus-mediated expression of cytokine-induced neutrophil chemoattractant in rat liver induces a neutrophilic hepatitis.
Hepatology (Baltimore, Md.)
Exploring alcohol's effects on liver function.
Alcohol health and research world
Rat hepatocytes and Kupffer cells interact to produce interleukin-8 (CINC) in the setting of ethanol.
The American journal of physiology
Malondialdehyde stimulates collagen production by hepatic lipocytes only upon activation in primary culture.
Alcohol and alcoholism (Oxford, Oxfordshire)
Acetaldehyde-induced stimulation of collagen synthesis and gene expression is dependent on conditions of cell culture: studies with rat lipocytes and fibroblasts.
Alcoholism, clinical and experimental research
Partial cloning of the M subunit of laminin from adult rat lipocytes: expression of the M subunit by cells isolated from normal and injured liver.
Hepatology (Baltimore, Md.)
Cell-matrix interactions in liver.
Seminars in cell biology
Cell-specific expression of hepatocyte growth factor in liver. Upregulation in sinusoidal endothelial cells after carbon tetrachloride.
The Journal of clinical investigation
Parenchymal and nonparenchymal cell interactions in the liver.
Seminars in liver disease
Inhibition of rat hepatic lipocyte activation in culture by interferon-gamma.
Hepatology (Baltimore, Md.)
Isolated hepatic lipocytes and Kupffer cells from normal human liver: morphological and functional characteristics in primary culture.
Hepatology (Baltimore, Md.)
Yet another role for the "good" matrix protein: laminin in regenerating liver.
Hepatology (Baltimore, Md.)
Extracellular matrix gene expression increases preferentially in rat lipocytes and sinusoidal endothelial cells during hepatic fibrosis in vivo.
The Journal of clinical investigation
Connective tissue biology and hepatic fibrosis: report of a conference.
Hepatology (Baltimore, Md.)
Hepatic fibrosis caused by alcohol.
Seminars in liver disease
Fat-storing cells and myofibroblasts: one cell or two?
Hepatology (Baltimore, Md.)
Primary hepatocyte culture: is it home away from home?
Hepatology (Baltimore, Md.)
Collagen measured in primary cultures of normal rat hepatocytes derives from lipocytes within the monolayer.
The Journal of clinical investigation
Immunolocalization of laminin in normal rat liver and biosynthesis of laminin by hepatic lipocytes in primary culture.
Gastroenterology
Support of cultured hepatocytes by a laminin-rich gel. Evidence for a functionally significant subendothelial matrix in normal rat liver.
The Journal of clinical investigation