A5038597279- Alcohol Consumption and Health Effects
- Liver Disease Diagnosis and Treatment
- Eicosanoids and Hypertension Pharmacology
- Neuroinflammation and Neurodegeneration Mechanisms
- Fatty Acid Research and Health
- Diet, Metabolism, and Disease
- Organ Transplantation Techniques and Outcomes
- Immune cells in cancer
- Complement system in diseases
- Liver physiology and pathology
- Epigenetics and DNA Methylation
- RNA Interference and Gene Delivery
- Tryptophan and brain disorders
- Angiogenesis and VEGF in Cancer
- Liver Disease and Transplantation
- Cancer, Hypoxia, and Metabolism
- Immune Response and Inflammation
- Cardiac Valve Diseases and Treatments
- Aortic Disease and Treatment Approaches
- Lymphatic System and Diseases
- Genomics, phytochemicals, and oxidative stress
- Endoplasmic Reticulum Stress and Disease
- Pituitary Gland Disorders and Treatments
- Effects and risks of endocrine disrupting chemicals
- Dietary Effects on Health
University of Colorado Anschutz Medical Campus
2016-2025
University of Montana
2016-2025
Center for Digestive and Liver Diseases
2017-2025
University of Colorado Denver
2020-2022
Cleveland Clinic
2014-2020
Cleveland Clinic Lerner College of Medicine
2016-2018
Case Western Reserve University
2018
Stanford University
2009
Multiple pathways of programmed cell death are important in liver homeostasis. Hepatocyte is associated with progression nonalcoholic fatty disease, and inhibition apoptosis partially protects against injury response to a high‐fat diet (HFD). However, the contribution necroptosis, caspase‐independent pathway death, HFD‐induced not known. Wild‐type C57BL/6 receptor interacting protein (RIP) 3 −/− mice were randomized chow or HFD. HFD‐fed increased expression RIP3, master regulator as well...
Chronic, systemic inflammation is a pathophysiological manifestation of metabolic disorders. Inflammatory signaling leads to elevated glycolytic flux and shift towards aerobic glycolysis lactate generation. This rise in corresponds with increased generation lactoylLys modifications on histones, mediating transcriptional responses inflammatory stimuli. Lactoylation also generated through non-enzymatic S-to-N acyltransfer from the glyoxalase cycle intermediate, lactoylglutathione (LGSH). Here,...
Binge alcohol use is increasing among aged adults (>65 years). Alcohol-related toxicity in associated with neurodegeneration, yet the molecular underpinnings of this age-related sensitivity to are not well described. Studies utilizing rodent models neurodegenerative disease reveal heightened activation Nuclear factor kappa-light-chain-enhancer activated B cells (NF-κB) and Nod like receptor 3 (NLRP3) mediate microglia neuronal injury. Our group, others, have implicated hippocampal-resident...
Complement plays a crucial role in microbial defense and clearance of apoptotic cells. Emerging evidence suggests complement is an important contributor to alcoholic liver disease. While component 1, Q subcomponent (C1q)-dependent activation contributes ethanol-induced injury, the alternative pathway injury unknown. Activation via classical pathways was detected hepatitis patients. Female C57BL/6J [wild type (WT)], C1q-deficient ( C1qa −/− , lacking activation), protein 4-deficient C4 lectin...
Abstract TLR4 signaling in hepatic macrophages is increased after chronic ethanol feeding. Treatment of feeding with small-specific sized hyaluronic acid 35 (HA35) normalizes signaling; however, the mechanisms for HA35 action are not completely understood. Here we used Next Generation Sequencing microRNAs to identify negative regulators reciprocally modulated by and macrophages. Eleven were up-regulated ethanol; only 4 microRNAs, including miR291b, decreased HA35. Bioinformatics analysis...
As a metabolic center, the liver prevents inappropriate immune responses to abundant dietary antigens within that could result in injury. This self-preservation mechanism can however decrease efficiency of immunosurveillance malignant cells by CD8 T cells. Hepatocellular carcinoma (HCC) is initiated chronic viral infections, alcohol consumption, and/or fatty diet leads injury, fibrosis, and cirrhosis. HCC patients have high levels dysfunctional exhausted cells, however, it unclear which...
Few series have examined follow-up risks of the David reimplantation operation in patients with connective tissue disorder. Hence, we assessed its midterm safety and effectiveness for Marfan syndrome other disorders, such as Ehlers-Danlos, Loeys-Dietz, marfanoid syndromes.Of 313 who underwent modified reimplantation, 178 identified having disorders from January 1, 1991, to December 31, 2010. These included (84%), (8.4%), Loeys-Dietz (5.6%), Ehlers-Danlos (1.1%), syndromes (1.1%). Concomitant...
Given the lack of effective therapies and high mortality in acute alcohol-associated hepatitis (AH), it is important to develop rationally designed biomarkers for disease management. Complement, a critical component innate immune system, contributes uncontrolled inflammatory responses leading liver injury, but also involved hepatic regeneration. Here, we investigated whether panel complement proteins activation products would provide useful severity AH aid predicting 90-day mortality.
Background & Aims: Chronic ethanol exposure results in inflammation adipose tissue; this response is associated with activation of complement as well the development alcohol-related liver disease (ALD). Adipose communicates other organs, including liver, via release soluble mediators, such adipokines and cytokines, characterized "adipose secretome". Here we investigated role anaphaylatoxin receptors C3aR C5aR1 tissue regulation secretome murine ALD (mALD). Methods: Wild-type C57BL/6 (WT),...
Background and Aims Despite the high clinical significance of sarcopenia in alcohol‐associated cirrhosis, there are currently no effective therapies because underlying mechanisms poorly understood. We determined ethanol‐induced impaired phosphorylation mechanistic target rapamycin complex 1 (mTORC1) adenosine monophosphate–activated protein kinase (AMPK) with consequent dysregulated skeletal muscle homeostasis (balance between synthesis breakdown). Approach Results Differentiated murine...
The global population of people over the age 65 is increasing and expected to reach 1.5 billion by 2050. While aging associated with a number chronic illnesses including dementia, underlying contribution alcohol misuse in elderly understudied. Long-term can lead alcohol-associated liver disease, consisting spectrum pathologies, steatosis cirrhosis; disease be rapidly accelerated non-resolving inflammation. Despite this knowledge, mechanistic underpinnings dysregulated host immunity...
Binge alcohol use is increasing among aged adults (>65 years). Alcohol-related toxicity in associated with neurodegeneration, yet the molecular underpinnings of age-related sensitivity to are not well described. Studies utilizing rodent models neurodegenerative disease reveal heightened activation Nuclear factor kappa-light-chain-enhancer activated B cells (NF-κB) and Nod like receptor 3 (NLRP3) mediate microglia neuronal injury. Our group, others, have implicated hippocampal-resident as key...
Toxicant exposure can lead to acute liver injury, characterized by hepatic reprogramming and wound healing. Hepatic stellate cells (HSC) play a key role in regeneration during healing secreting fibrogenic factors production of extracellular matrix (ECM). However, repetitive injury the extensive scarring fibrosis, indicating HSCs coordinate both disease. Because contributing HSC are not fully defined, we sought further characterize morphogenic pathways an model toxicant-induced injury1....