Michael Karin
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View article: Endoplasmic reticulum stress at the forefront of fatty liver diseases and cancer
Endoplasmic reticulum stress at the forefront of fatty liver diseases and cancer Open
The endoplasmic reticulum (ER) is a dynamic membranous organelle that accounts for nearly half of the total membrane content in hepatocytes and serves as a central hub for protein folding and lipid biosynthesis. Given the liver's essential…
View article: Obesity Related Microbial Dysbiosis as a Potential Modulator of Tumor Progression
Obesity Related Microbial Dysbiosis as a Potential Modulator of Tumor Progression Open
Although there is a well-established connection between the gut microbiome and obesity, the specific mechanisms by which microbes regulate cell signaling, inflammation, and adipocyte growth to influence disease severity in obese patients r…
View article: Obesity-related microbial dysbiosis as a potential modulator of tumour progression
Obesity-related microbial dysbiosis as a potential modulator of tumour progression Open
Although there is a well-established connection between the gut microbiome and obesity, the specific mechanisms by which microbes regulate cell signalling, inflammation and adipocyte growth to influence disease severity in obese patients r…
View article: Self-amplifying NRF2–EZH2 epigenetic loop converts KRAS-initiated progenitors to invasive pancreatic cancer
Self-amplifying NRF2–EZH2 epigenetic loop converts KRAS-initiated progenitors to invasive pancreatic cancer Open
View article: Author Correction: Collagenolysis-dependent DDR1 signalling dictates pancreatic cancer outcome
Author Correction: Collagenolysis-dependent DDR1 signalling dictates pancreatic cancer outcome Open
View article: FAMES analysis v1
FAMES analysis v1 Open
Fatty acid methyl ester (FAMES) analysis was used to measure glucose-derived carbon incorporation into fatty acids in KrasG12D/PEC organoids. Organoids were labeled with [U-¹³C₆] glucose, extracted, derivatized, and analyzed by GC-MS. Quan…
View article: Histopathology and Immunohistochemistry v1
Histopathology and Immunohistochemistry v1 Open
Histopathology and immunohistochemistry (IHC) were performed on pancreatic tissue sections and tissue microarrays (TMAs). Tissues were fixed, embedded in paraffin, and sectioned for staining with hematoxylin and eosin (H&E). For IHC, secti…
View article: ChIPseq libraries preparation v1
ChIPseq libraries preparation v1 Open
ChIP-seq was performed to analyze H3K27ac and H3K27me3 in CTRL and EZH2KO UN-KC6141 cells. Cells were crosslinked, lysed, and sonicated. Chromatin was immunoprecipitated using specific antibodies and Protein G Dynabeads. Libraries were pre…
View article: RNAseq libraries preparation, analysis and data processing v1
RNAseq libraries preparation, analysis and data processing v1 Open
RNAseq libraries were prepared from mouse pancreata and murine cell lines (CTRL, EZH2KO, EEDKO UN-KC6141) following standard protocols. After RNA extraction and poly-A enrichment, libraries were generated and sequenced on HiSeq 4000 or Nex…
View article: Protein extraction, co-immunoprecipitation, and immunoblots v2
Protein extraction, co-immunoprecipitation, and immunoblots v2 Open
Protein extraction, co-immunoprecipitation, and immunoblotting were performed in both mouse and human cell lines, as well as in mouse pancreatic tissue. The main steps used in these experiments are described in the manuscript by Antonucci …
View article: Author Correction: FBP1 controls liver cancer evolution from senescent MASH hepatocytes
Author Correction: FBP1 controls liver cancer evolution from senescent MASH hepatocytes Open
View article: Innate immune cells link dietary cues to normal and abnormal metabolic regulation
Innate immune cells link dietary cues to normal and abnormal metabolic regulation Open
View article: FBP1 controls liver cancer evolution from senescent MASH hepatocytes
FBP1 controls liver cancer evolution from senescent MASH hepatocytes Open
View article: Mitochondrial DNA oxidation propagates autoimmunity by enabling plasmacytoid dendritic cells induce Tfh differentiation
Mitochondrial DNA oxidation propagates autoimmunity by enabling plasmacytoid dendritic cells induce Tfh differentiation Open
NLRP3 inflammasome activation depends on stress-induced production of oxidized mitochondrial DNA (Ox-mtDNA) fragments that enter the cytoplasm to bind NLRP3 and activate caspase-1. Along with pro-IL-1β processing, caspase-1 generates gasde…
View article: Rejuvenation driven reprograming in T lymphocytes
Rejuvenation driven reprograming in T lymphocytes Open
Rejuvenation restores cellular function lost with age, but it is not known to confer properties the cell lacked in its younger past. We found that Disruptors of sestrin-MAPK interactions (DOS) reprogramed senescent T cells into new stem li…
View article: IL-22 resolves MASLD via enterocyte STAT3 restoration of diet-perturbed intestinal homeostasis
IL-22 resolves MASLD via enterocyte STAT3 restoration of diet-perturbed intestinal homeostasis Open
The exponential rise in metabolic dysfunction-associated steatotic liver disease (MASLD) parallels the ever-increasing consumption of energy-dense diets, underscoring the need for effective MASLD-resolving drugs. MASLD pathogenesis is link…
View article: Disruptors of sestrin-MAPK interactions rejuvenate T cells and expand TCR specificity
Disruptors of sestrin-MAPK interactions rejuvenate T cells and expand TCR specificity Open
Summary Whereas treatments that reactivate exhausted T cells are available, strategies to rejuvenate terminally differentiated senescent lymphocytes are yet to be developed. Senescent T cells, with short telomeres and inactive telomerase, …
View article: Triclosan administration to humanized UDP-glucuronosyltransferase 1 neonatal mice induces UGT1A1 through a dependence on PPARα and ATF4
Triclosan administration to humanized UDP-glucuronosyltransferase 1 neonatal mice induces UGT1A1 through a dependence on PPARα and ATF4 Open
Triclosan (TCS) is an antimicrobial toxicant found in a myriad of consumer products and has been detected in human tissues, including breastmilk. We have evaluated the impact of lactational TCS on UDP-glucuronosyltransferase 1A1 (UGT1A1) e…
View article: IRF1 regulates self-renewal and stress responsiveness to support hematopoietic stem cell maintenance
IRF1 regulates self-renewal and stress responsiveness to support hematopoietic stem cell maintenance Open
Hematopoietic stem cells (HSCs) are tightly controlled to maintain a balance between blood cell production and self-renewal. While inflammation-related signaling is a critical regulator of HSC activity, the underlying mechanisms and the pr…
View article: Therapeutic blockade of ER stress and inflammation prevents NASH and progression to HCC
Therapeutic blockade of ER stress and inflammation prevents NASH and progression to HCC Open
The incidence of hepatocellular carcinoma (HCC) is rapidly rising largely because of increased obesity leading to nonalcoholic steatohepatitis (NASH), a known HCC risk factor. There are no approved treatments to treat NASH. Here, we first …
View article: Multifaceted collagen-DDR1 signaling in cancer
Multifaceted collagen-DDR1 signaling in cancer Open
View article: Effects of Early Life Oral Arsenic Exposure on Intestinal Tract Development and Lipid Homeostasis in Neonatal Mice: Implications for NAFLD Development
Effects of Early Life Oral Arsenic Exposure on Intestinal Tract Development and Lipid Homeostasis in Neonatal Mice: Implications for NAFLD Development Open
Exposure to iAs in neonatal mice resulted in excessive accumulation of fat in enterocytes, disrupting lipid homeostasis in the serum and liver, revealing the importance of the gut-liver axis and endoplasmic reticulum stress in mediating iA…
View article: Macrophage Xanthine Oxidoreductase Links LPS Induced Lung Inflammatory Injury to NLRP3 Inflammasome Expression and Mitochondrial Respiration
Macrophage Xanthine Oxidoreductase Links LPS Induced Lung Inflammatory Injury to NLRP3 Inflammasome Expression and Mitochondrial Respiration Open
SUMMARY Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) remain poorly treated inflammatory lung disorders. Both reactive oxygen species (ROS) and macrophages are involved in the pathogenesis of ALI/ARDS. Xanthine…
View article: Signalling by senescent melanocytes hyperactivates hair growth
Signalling by senescent melanocytes hyperactivates hair growth Open
Niche signals maintain stem cells in a prolonged quiescence or transiently activate them for proper regeneration 1 . Altering balanced niche signalling can lead to regenerative disorders. Melanocytic skin nevi in human often display excess…
View article: Author Correction: A central role for JNK in obesity and insulin resistance
Author Correction: A central role for JNK in obesity and insulin resistance Open
View article: Single-nucleus RNA sequencing of pre-malignant liver reveals disease-associated hepatocyte state with HCC prognostic potential
Single-nucleus RNA sequencing of pre-malignant liver reveals disease-associated hepatocyte state with HCC prognostic potential Open
View article: Data from Concurrent Disruption of the Ras/MAPK and NF-κB Pathways Induces Circadian Deregulation and Hepatocarcinogenesis
Data from Concurrent Disruption of the Ras/MAPK and NF-κB Pathways Induces Circadian Deregulation and Hepatocarcinogenesis Open
The Ras/Erk and NF-κB pathways play critical roles in cell proliferation and are known to drive oncogenesis when overactivated. Herein we report a gatekeeper function of the two pathways by working in synergy to suppress liver tumorigenesi…
View article: Data from Concurrent Disruption of the Ras/MAPK and NF-κB Pathways Induces Circadian Deregulation and Hepatocarcinogenesis
Data from Concurrent Disruption of the Ras/MAPK and NF-κB Pathways Induces Circadian Deregulation and Hepatocarcinogenesis Open
The Ras/Erk and NF-κB pathways play critical roles in cell proliferation and are known to drive oncogenesis when overactivated. Herein we report a gatekeeper function of the two pathways by working in synergy to suppress liver tumorigenesi…
View article: Supplementary Data from Concurrent Disruption of the Ras/MAPK and NF-κB Pathways Induces Circadian Deregulation and Hepatocarcinogenesis
Supplementary Data from Concurrent Disruption of the Ras/MAPK and NF-κB Pathways Induces Circadian Deregulation and Hepatocarcinogenesis Open
Supplementary Data from Concurrent Disruption of the Ras/MAPK and NF-κB Pathways Induces Circadian Deregulation and Hepatocarcinogenesis
View article: Supplementary figure 1 from Characterization of HCC Mouse Models: Towards an Etiology-Oriented Subtyping Approach
Supplementary figure 1 from Characterization of HCC Mouse Models: Towards an Etiology-Oriented Subtyping Approach Open
guide to murine tumor analysis