Steven Dooley
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View article: Transforming Growth Factor-β Signaling in Alcohol-Associated Liver Disease
Transforming Growth Factor-β Signaling in Alcohol-Associated Liver Disease Open
Transforming growth factor-β (TGF-β) signaling exerts broad regulatory effects on alcohol-associated liver disease (ALD) progression, influencing processes such as hepatocellular injury, regeneration, inflammation, fibrogenesis, cirrhosis,…
View article: The interplay between biomechanics and cell kinetics explains the spatial pattern in liver fibrosis
The interplay between biomechanics and cell kinetics explains the spatial pattern in liver fibrosis Open
The formation of liver fibrosis patterns, characterized by excess extracellular matrix (ECM), is a complex process that is difficult to investigate experimentally. To complement experimental approaches, we developed a digital twin (DT) mod…
View article: ECM1 expression in chronic liver disease: Regulation by EGF/STAT1 and IFNγ/NRF2 signalling
ECM1 expression in chronic liver disease: Regulation by EGF/STAT1 and IFNγ/NRF2 signalling Open
This study reveals the regulatory mechanism of ECM1 in hepatocytes, demonstrating that EGF/STAT1 maintains ECM1 expression to prevent fibrosis, whereas IFNγ/NRF2 signalling inhibits ECM1 during chronic liver inflammation, thereby accelerat…
View article: Role of WISP1 in Stellate Cell Migration and Liver Fibrosis
Role of WISP1 in Stellate Cell Migration and Liver Fibrosis Open
The mechanisms underlying the remarkable capacity of the liver to regenerate are still not completely understood. Particularly, the cross-talk between cytokines and cellular components of the process is of utmost importance because they re…
View article: Retinoic acid generates a beneficial microenvironment for liver progenitor cell activation in acute liver failure
Retinoic acid generates a beneficial microenvironment for liver progenitor cell activation in acute liver failure Open
Background: When massive necrosis occurs in acute liver failure (ALF), rapid expansion of HSCs called liver progenitor cells (LPCs) in a process called ductular reaction is required for survival. The underlying mechanisms governing this pr…
View article: ERRγ-inducible FGF23 promotes alcoholic liver injury through enhancing CYP2E1 mediated hepatic oxidative stress
ERRγ-inducible FGF23 promotes alcoholic liver injury through enhancing CYP2E1 mediated hepatic oxidative stress Open
Fibroblast growth factor 23 (FGF23) is a member of endocrine FGF family, along with FGF15/19 and FGF21. Recent reports showed that under pathological conditions, liver produces FGF23, although the role of hepatic FGF23 remains nebulous. He…
View article: Dynamic YAP expression in the non-parenchymal liver cell compartment controls heterologous cell communication
Dynamic YAP expression in the non-parenchymal liver cell compartment controls heterologous cell communication Open
Introduction The Hippo pathway and its transcriptional effectors yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are targets for cancer therapy. It is important to determine if the activation of on…
View article: TGFβR1 inhibition drives hepatocellular carcinoma proliferation through induction of toll‐like‐receptor signalling
TGFβR1 inhibition drives hepatocellular carcinoma proliferation through induction of toll‐like‐receptor signalling Open
Transforming growth factor (TGF)‐β and toll‐like receptors (TLRs) have been shown to independently modulate the proliferation of hepatocellular carcinoma (HCC). Since a direct cross‐talk between these two signalling pathways in HCC has not…
View article: Retinoic acid generates a beneficial microenvironment for liver progenitor cell activation in acute liver failure
Retinoic acid generates a beneficial microenvironment for liver progenitor cell activation in acute liver failure Open
Objective When massive necrosis occurs in acute liver failure (ALF), rapid expansion of hepatic stem cells called liver progenitor cells (LPC) in a process called ductular reaction (DR) is required for survival. The exact underlying mechan…
View article: ECM1 Attenuates Hepatic Fibrosis by Interfering with Mediators of Latent TGF-β1 Activation
ECM1 Attenuates Hepatic Fibrosis by Interfering with Mediators of Latent TGF-β1 Activation Open
Objective: Extracellular Matrix Protein 1 (ECM1) serves as a gatekeeper of hepatic fibrosis by maintaining transforming growth factor-β1 (TGF-β1) in its latent form. ECM1 knockout (KO) causes latent (L) TGF-β1 activation, resulting in hepa…
View article: FOXA2 is essential for maintaining the urea cycle in acute liver failure
FOXA2 is essential for maintaining the urea cycle in acute liver failure Open
Hepatic encephalopathy is a lethal complication of acute liver failure (ALF), and is caused by hyperammonemia. Ammonia clearance by the liver requires an intact and complete urea cycle comprising six enzymes, including the rate-limiting en…
View article: Rapid dexamethasone treatment inhibits LPS-induced cytokine storm in mice
Rapid dexamethasone treatment inhibits LPS-induced cytokine storm in mice Open
Severe infection-induced cytokine storm is an urgent medical syndrome with high mortality. To date, no therapy is available. This study shows that high concentrations of lipopolysaccharide (LPS) induce cytokine storm within 48h and thus ki…
View article: A liver digital twin for in silico testing of cellular and inter-cellular mechanisms in regeneration after drug-induced damage
A liver digital twin for in silico testing of cellular and inter-cellular mechanisms in regeneration after drug-induced damage Open
This communication presents a mathematical mechanism-based model of the regenerating liver after drug-induced pericentral lobule damage resolving tissue microarchitecture. The consequence of alternative hypotheses about the interplay of di…
View article: Cholesterol modulates type I-type II TGF-β receptor complexes and alters the balance between Smad and Akt signaling in hepatocytes
Cholesterol modulates type I-type II TGF-β receptor complexes and alters the balance between Smad and Akt signaling in hepatocytes Open
Cholesterol mediates membrane compartmentalization, affecting signaling via differential distribution of receptors and signaling mediators. While excessive cholesterol and aberrant transforming growth factor-β (TGF-β) signaling characteriz…
View article: Hepatocytes reprogram liver macrophages involving control of TGF-β activation, influencing liver regeneration and injury
Hepatocytes reprogram liver macrophages involving control of TGF-β activation, influencing liver regeneration and injury Open
Background: Macrophages play an important role in maintaining liver homeostasis and regeneration. However, it is not clear to what extent the different macrophage populations of the liver differ in terms of their activation state and which…
View article: Insulin determines the effects of TGF-β on HNF4α transcription and epithelial-to-mesenchymal transition in hepatocytes
Insulin determines the effects of TGF-β on HNF4α transcription and epithelial-to-mesenchymal transition in hepatocytes Open
To date, epithelial-to-mesenchymal transition (EMT) has been observed in cultured hepatocytes, but not in vivo . TGF-β is supposed to initiate EMT in hepatocytes by inhibiting HNF4 α through the SMAD2/3 complex. We report that TGF- β does …
View article: The Functional Architecture of Personalized & Precision Medicine (PPM) Driven by Innovative Strategies to Secure the Clinical Impact and Implementation to Cancer Management: Brief Comments
The Functional Architecture of Personalized & Precision Medicine (PPM) Driven by Innovative Strategies to Secure the Clinical Impact and Implementation to Cancer Management: Brief Comments Open
The medicine of the XXI century is Personalized & Precision Medicine (PPM), by protecting and preserving human health throughout the life. Creating and maintaining a high level of public health and thus the wellness is a priority in the he…
View article: Tolerance of repeated toxic injuries of murine livers is associated with steatosis and inflammation
Tolerance of repeated toxic injuries of murine livers is associated with steatosis and inflammation Open
The human liver has a remarkable capacity to regenerate and thus compensate over decades for fibrosis caused by toxic chemicals, drugs, alcohol, or malnutrition. To date, no protective mechanisms have been identified that help the liver to…
View article: Serum Glial Cell Line-Derived Neurotrophic Factor (sGDNF) Is a Novel Biomarker in Predicting Cirrhosis in Patients with Chronic Hepatitis B
Serum Glial Cell Line-Derived Neurotrophic Factor (sGDNF) Is a Novel Biomarker in Predicting Cirrhosis in Patients with Chronic Hepatitis B Open
Objectives. We assessed the potential of glial cell line-derived neurotrophic factor (GDNF) as a useful biomarker to predict cirrhosis in chronic hepatitis B (CHB) patients. Methods. A total of 735 patients from two medical centers (385 CH…