William M. Pandak
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View article: StarD5 Plays a Critical Role in the Hepatocyte ER Stress Survival Response
StarD5 Plays a Critical Role in the Hepatocyte ER Stress Survival Response Open
The unfolded protein response (UPR) is a highly orchestrated survival response initiated in cells under endoplasmic reticulum (ER) stress. Steroidogenic acute regulatory-related lipid transfer domain 5 (StarD5) is an ER stress-responsive, …
View article: Liver specific transgenic expression of CYP7B1 attenuates early western diet-induced MASLD progression
Liver specific transgenic expression of CYP7B1 attenuates early western diet-induced MASLD progression Open
Effect of liver specific oxysterol 7α-hydroxylase (CYP7B1) overexpression on the Western diet (WD)-induced metabolic dysfunction-associated steatotic liver disease (MASLD) progression was studied in mice. Among various hepatic genes impact…
View article: StarD5 modulates B cell cholesterol synthesis and IgG1 plasma cell differentiation
StarD5 modulates B cell cholesterol synthesis and IgG1 plasma cell differentiation Open
View article: StarD5 levels of expression correlate with onset and progression of steatosis and liver fibrosis
StarD5 levels of expression correlate with onset and progression of steatosis and liver fibrosis Open
We have found that deletion of the cholesterol transport protein StarD5 in mice leads to an increase in insulin resistance and lipid accumulation due to the upregulation of lipid synthesis and decrease VLDL secretion from the liver. In add…
View article: Baseline Features and Reasons for Nonparticipation in the Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) Study, a Colorectal Cancer Screening Trial
Baseline Features and Reasons for Nonparticipation in the Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) Study, a Colorectal Cancer Screening Trial Open
Importance The Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) randomized clinical trial sought to recruit 50 000 adults into a study comparing colorectal cancer (CRC) mortality outcomes …
View article: Mitochondrial Cholesterol Metabolites in a Bile Acid Synthetic Pathway Drive Nonalcoholic Fatty Liver Disease: A Revised “Two-Hit” Hypothesis
Mitochondrial Cholesterol Metabolites in a Bile Acid Synthetic Pathway Drive Nonalcoholic Fatty Liver Disease: A Revised “Two-Hit” Hypothesis Open
The rising prevalence of nonalcoholic fatty liver disease (NAFLD)-related cirrhosis highlights the need for a better understanding of the molecular mechanisms responsible for driving the transition of hepatic steatosis (fatty liver; NAFL) …
View article: Insulin dysregulation drives mitochondrial cholesterol metabolite accumulation: initiating hepatic toxicity in nonalcoholic fatty liver disease
Insulin dysregulation drives mitochondrial cholesterol metabolite accumulation: initiating hepatic toxicity in nonalcoholic fatty liver disease Open
CYP7B1 catalyzes mitochondria-derived cholesterol metabolites such as (25R)26-hydroxycholesterol (26HC) and 3β-hydroxy-5-cholesten-(25R)26-oic acid (3βHCA) and facilitates their conversion to bile acids. Disruption of 26HC/3βHCA metabolism…
View article: Coffee modulates insulin-hepatocyte nuclear factor-4α-Cyp7b1 pathway and reduces oxysterol-driven liver toxicity in a nonalcoholic fatty liver disease mouse model
Coffee modulates insulin-hepatocyte nuclear factor-4α-Cyp7b1 pathway and reduces oxysterol-driven liver toxicity in a nonalcoholic fatty liver disease mouse model Open
This study demonstrated dietary coffee prevented the accumulation of hepatic oxysterols by maintaining Cyp7b1/Sult2b1 expression in a diet-induced NAFLD mice model. Lowering liver oxysterols markedly reduced inflammation in the coffee-inge…
View article: 25-Hydroxycholesterol 3-Sulfate Recovers Acetaminophen Induced Acute Liver Injury via Stabilizing Mitochondria in Mouse Models
25-Hydroxycholesterol 3-Sulfate Recovers Acetaminophen Induced Acute Liver Injury via Stabilizing Mitochondria in Mouse Models Open
Acetaminophen (APAP) overdose is one of the most frequent causes of acute liver failure (ALF). N-acetylcysteine (NAC) is currently being used as part of the standard care in the clinic but its usage has been limited in severe cases, in whi…
View article: Berberine Prevents Disease Progression of Nonalcoholic Steatohepatitis through Modulating Multiple Pathways
Berberine Prevents Disease Progression of Nonalcoholic Steatohepatitis through Modulating Multiple Pathways Open
Background and Aims: The disease progression of nonalcoholic fatty liver disease (NAFLD) from simple steatosis (NAFL) to nonalcoholic steatohepatitis (NASH) is driven by multiple factors. Berberine (BBR) is an ancient Chinese medicine and …
View article: Insulin resistance dysregulates CYP7B1 leading to oxysterol accumulation: a pathway for NAFL to NASH transition
Insulin resistance dysregulates CYP7B1 leading to oxysterol accumulation: a pathway for NAFL to NASH transition Open
View article: High Glucose Induces Lipid Accumulation via 25-Hydroxycholesterol DNA-CpG Methylation
High Glucose Induces Lipid Accumulation via 25-Hydroxycholesterol DNA-CpG Methylation Open
View article: Rifaximin Exerts Beneficial Effects Independent of its Ability to Alter Microbiota Composition
Rifaximin Exerts Beneficial Effects Independent of its Ability to Alter Microbiota Composition Open
Rifaximin has clinical benefits in minimal hepatic encephalopathy (MHE) but the mechanism of action is unclear. The antibiotic-dependent and -independent effects of rifaximin need to be elucidated in the setting of MHE-associated microbiot…
View article: Microbial functional change is linked with clinical outcomes after capsular fecal transplant in cirrhosis
Microbial functional change is linked with clinical outcomes after capsular fecal transplant in cirrhosis Open
BACKGROUNDHepatic encephalopathy (HE) is associated with poor outcomes. A prior randomized, pilot trial demonstrated safety after oral capsular fecal microbial transplant (FMT) in HE, with favorable changes in microbial composition and cog…
View article: The acidic pathway of bile acid synthesis: Not just an alternative pathway
The acidic pathway of bile acid synthesis: Not just an alternative pathway Open
View article: 243 – Stard5 Plays a Critical Role in the Hepatocyte Er Stress Survival Response
243 – Stard5 Plays a Critical Role in the Hepatocyte Er Stress Survival Response Open
View article: StarD5: an ER stress protein regulates plasma membrane and intracellular cholesterol homeostasis
StarD5: an ER stress protein regulates plasma membrane and intracellular cholesterol homeostasis Open
View article: Cholangiocyte‐Derived Exosomal Long Noncoding RNA H19 Promotes Hepatic Stellate Cell Activation and Cholestatic Liver Fibrosis
Cholangiocyte‐Derived Exosomal Long Noncoding RNA H19 Promotes Hepatic Stellate Cell Activation and Cholestatic Liver Fibrosis Open
Activation of hepatic stellate cells (HSCs) represents the primary driving force to promote the progression of chronic cholestatic liver diseases. We previously reported that cholangiocyte‐derived exosomal long noncoding RNA‐H19 (lncRNA‐H1…
View article: Alterations in Skin Microbiomes of Patients With Cirrhosis
Alterations in Skin Microbiomes of Patients With Cirrhosis Open
View article: Alterations in gut microbial function following liver transplant
Alterations in gut microbial function following liver transplant Open
Liver transplantation (LT) improves daily function and ameliorates gut microbial composition. However, the effect of LT on microbial functionality, which can be related to overall patient benefit, is unclear and could affect the post‐LT co…
View article: Cholangiocyte‐derived exosomal long noncoding RNA H19 promotes cholestatic liver injury in mouse and humans
Cholangiocyte‐derived exosomal long noncoding RNA H19 promotes cholestatic liver injury in mouse and humans Open
Cholestatic liver injury is an important clinical problem with limited understanding of disease pathologies. Exosomes are small extracellular vesicles released by a variety of cells, including cholangiocytes. Exosome‐mediated cell‐cell com…
View article: C/EBP homologous protein–induced loss of intestinal epithelial stemness contributes to bile duct ligation–induced cholestatic liver injury in mice
C/EBP homologous protein–induced loss of intestinal epithelial stemness contributes to bile duct ligation–induced cholestatic liver injury in mice Open
Activation of ER stress and subsequent loss of stemness of ISCs plays a critical role in BDL-induced systemic inflammation and cholestatic liver injury. Modulation of the ER stress response represents a potential therapeutic strategy for c…
View article: The role of long noncoding RNA H19 in gender disparity of cholestatic liver injury in multidrug resistance 2 gene knockout mice
The role of long noncoding RNA H19 in gender disparity of cholestatic liver injury in multidrug resistance 2 gene knockout mice Open
The multidrug resistance 2 knockout ( Mdr2 –/– ) mouse is a well‐established model of cholestatic cholangiopathies. Female Mdr2 –/– mice develop more severe hepatobiliary damage than male Mdr2 –/– mice, which is correlated with a higher pr…
View article: Gut microbial composition can differentially regulate bile acid synthesis in humanized mice
Gut microbial composition can differentially regulate bile acid synthesis in humanized mice Open
We previously reported that alcohol drinkers with and without cirrhosis showed a significant increase in fecal bile acid secretion compared to nondrinkers. We hypothesized this may be due to activation by alcohol of hepatic cyclic adenosin…
View article: Issue Information
Issue Information Open
nor-UDCA, and UDCA; (C) obeticholic acid; (D) ustekinumab; (E) budesonide; (F) LUM001; (G) antibiotics in PSC; (H) BTT1023; (I) abatacept.
View article: The role of sphingosine 1‐phosphate receptor 2 in bile‐acid–induced cholangiocyte proliferation and cholestasis‐induced liver injury in mice
The role of sphingosine 1‐phosphate receptor 2 in bile‐acid–induced cholangiocyte proliferation and cholestasis‐induced liver injury in mice Open
Bile duct obstruction is a potent stimulus for cholangiocyte proliferation, especially for large cholangiocytes. Our previous studies reported that conjugated bile acids (CBAs) activate the protein kinase B (AKT) and extracellular signal‐r…
View article: Rifaximin Exerts Beneficial Effects Independent of its Ability to Alter Microbiota Composition
Rifaximin Exerts Beneficial Effects Independent of its Ability to Alter Microbiota Composition Open
Rifaximin beneficially alters intestinal ammonia generation by regulating intestinal glutaminase expression independent of gut microbiota. MHE-associated fecal colonization results in intestinal and systemic inflammation in GF mice, which …
View article: Human Placenta-derived Cells (PDA-001) for the Treatment of Moderate-to-severe Crohnʼs Disease
Human Placenta-derived Cells (PDA-001) for the Treatment of Moderate-to-severe Crohnʼs Disease Open
A 2-infusion regimen of PDA-001 induced clinical response in subjects with moderate-to-severe CD. Additional studies are warranted.
View article: Inhibition of insulin-like growth factor receptor/AKT/mammalian target of rapamycin axis targets colorectal cancer stem cells by attenuating mevalonate-isoprenoid pathway<i>in vitro</i>and<i>in vivo</i>
Inhibition of insulin-like growth factor receptor/AKT/mammalian target of rapamycin axis targets colorectal cancer stem cells by attenuating mevalonate-isoprenoid pathway<i>in vitro</i>and<i>in vivo</i> Open
We observed a co-upregulation of the insulin-like growth factor receptor (IGF-1R)/AKT/mammalian target of rapamycin (mTOR) [InAT] axis and the mevalonate-isoprenoid biosynthesis (MIB) pathways in colorectal cancer stem cells (CSCs) in an u…