A5084928760- Autophagy in Disease and Therapy
- Cardiovascular and exercise physiology
- Adipose Tissue and Metabolism
- High Altitude and Hypoxia
- Heart Rate Variability and Autonomic Control
- Immune cells in cancer
- Atherosclerosis and Cardiovascular Diseases
- Calcium signaling and nucleotide metabolism
- Diet and metabolism studies
- Inflammasome and immune disorders
- Cardiovascular Health and Disease Prevention
- Phagocytosis and Immune Regulation
- Endoplasmic Reticulum Stress and Disease
- Adipokines, Inflammation, and Metabolic Diseases
- Epigenetics and DNA Methylation
- Cancer, Lipids, and Metabolism
- Nitric Oxide and Endothelin Effects
- Bacterial Genetics and Biotechnology
- RNA modifications and cancer
- Muscle Physiology and Disorders
- Lysosomal Storage Disorders Research
- Diet, Metabolism, and Disease
- Microbial Metabolic Engineering and Bioproduction
- Mitochondrial Function and Pathology
- Extracellular vesicles in disease
Washington University in St. Louis
2014-2025
University of Colorado Boulder
2014-2020
Cardiovascular Research Center
2015-2018
Evans Analytical Group (United States)
2017
University of Wisconsin–Madison
2010-2015
Beijing Sport University
2011
Abstract Macrophages specialize in removing lipids and debris present the atherosclerotic plaque. However, plaque progression renders macrophages unable to degrade exogenous atherogenic material endogenous cargo including dysfunctional proteins organelles. Here we show that a decline autophagy–lysosome system contributes this as evidenced by derangement key autophagy markers both mouse human plaques. By augmenting macrophage TFEB, master transcriptional regulator of autophagy–lysosomal...
In the atherosclerotic plaque, macrophages are key catabolic workhorse responsible for clearing lipid and dead cell debris. To survive highly proinflammatory lipotoxic plaque environment, must adopt strategies maintaining tight homeostasis self-renewal. Macroautophagy/autophagy is a pro-survival cellular pathway wherein damaged or excess cargoes encapsulated by double-membrane compartment delivered to lysosome hydrolysis. Previously, macrophage-specific autophagy deficiency has been shown be...
Sequestration of aggregated proteins by p62 prevents macrophages from exacerbating atherosclerosis.
The autophagy-lysosome system is an important cellular degradation pathway that recycles dysfunctional organelles and cytotoxic protein aggregates. A decline in this pathogenic many human diseases including neurodegenerative disorders, fatty liver disease, atherosclerosis. Thus there intense interest discovering therapeutics aimed at stimulating the system. Trehalose a natural disaccharide composed of two glucose molecules linked by ɑ-1,1-glycosidic bond with unique ability to induce...
Age-associated skeletal muscle mass loss curtails quality of life and may contribute to defects in metabolic homeostasis older persons. The onset sarcopenia occurs middle age rhesus macaques although the trigger has yet be identified. Here, we show that a shift metabolism advance vastus lateralis. Multiphoton laser-scanning microscopy detects kinetics photon emission from autofluorescent cofactors NADH FAD. Lifetime both fluorophores is shortened at mid-age, this observed free bound...
Insufficient nitric oxide (NO) bioavailability plays an important role in endothelial dysfunction and arterial stiffening with aging. Supplementation sodium nitrite, a precursor of NO, ameliorates age-related vascular stiffness mice, but effects on humans, including the metabolic pathways altered, are unknown. The purpose this study was to determine safety, feasibility, efficacy oral nitrite supplementation for improving function middle-aged older adults identify related circulating...
Tumor-associated macrophages (TAMs) play key roles in the development of many malignant solid tumors including breast cancer. They are educated tumor microenvironment (TME) to promote growth, metastasis, and therapy resistance. However, phenotype TAMs is elusive how regulate them for therapeutic purpose remains unclear; therefore, TAM-targeting therapies have not yet achieved clinical success. The purposes this study were examine role transcription factor EB (TFEB) regulating TAM gene...
TFEB promotes the browning of white adipose tissue through mechanisms unrelated to autophagy.
The mTOR (mechanistic target of rapamycin) pathway is a complex signaling cascade that regulates cellular growth, proliferation, metabolism, and survival. Although activation has been linked to atherosclerosis, its direct role in lesion progression plaque macrophages remains poorly understood. We previously demonstrated mTORC1 (mTOR 1) promotes atherogenesis through inhibition autophagy increased apoptosis macrophages.
Abstract Adenosine-5’-triphosphate (ATP), the primary energy currency in cellular processes, drives metabolic activities and biosynthesis. Despite its importance, understanding intracellular ATP dynamics’ impact on bioproduction exploiting it for enhanced remains largely unexplored. Here, we harness an biosensor to dissect dynamics across different growth phases carbon sources multiple microbial strains. We find transient accumulations during transition from exponential stationary various...
Aging | doi:10.18632/aging.100842. Jamie N. Justice, Lawrence C. Johnson, Allison E. DeVan, Charmion Cruickshank-Quinn, Nichole Reisdorph, Candace J. Bassett, Trent D. Evans, Forrest A. Brooks, Nathan S. Bryan, Michel B. Chonchol, Tony Giordano, Matthew McQueen, Douglas R. Seals
Tumor microenvironment (TME) contains a variety of infiltrating immune cells. Among them, tumor-associated macrophages (TAMs) and their alternative activation contribute greatly to the progression tumors. The mechanisms governing macrophage polarization in TME are unclear. Here, we show that TAMs or under tumor-conditioned medium treatment, expression transcription factor EB (TFEB) is reduced more TFEB protein an inactive cytosolic form. Transforming growth (TGF)-β identified as main driving...
Adipose tissue lipolysis is the process by which triglycerides in lipid stores are hydrolyzed into free fatty acids (FFAs), serving as fuel during fasting or cold-induced thermogenesis. Although cytosolic lipases considered predominant mechanism of liberating FFAs, also occurs lysosomes via lysosomal acid lipase (LIPA), albeit with unclear roles storage and whole-body metabolism. We found that adipocyte LIPA expression increased adipose mice when was stimulated fasting, cold exposure,...
LIPA (lysosomal acid lipase) mediates cholesteryl ester hydrolysis, and patients with rare loss-of-function mutations develop hypercholesterolemia severe disease. Genome-wide association studies of coronary artery disease have identified several tightly linked, common intronic risk variants in which unexpectedly associate increased mRNA expression. However, an exonic variant (rs1051338 resulting T16P) linkage lies the signal peptide region putatively disrupts trafficking. We sought to...