A5077962312- Autophagy in Disease and Therapy
- Lipid metabolism and biosynthesis
- Adipose Tissue and Metabolism
- Endoplasmic Reticulum Stress and Disease
- Sleep and Wakefulness Research
- Calcium signaling and nucleotide metabolism
- Genetics, Aging, and Longevity in Model Organisms
- Cell death mechanisms and regulation
- Liver Disease Diagnosis and Treatment
- Cannabis and Cannabinoid Research
- Adipokines, Inflammation, and Metabolic Diseases
- Regulation of Appetite and Obesity
- Mitochondrial Function and Pathology
- Histone Deacetylase Inhibitors Research
- PI3K/AKT/mTOR signaling in cancer
- Circadian rhythm and melatonin
- Mechanisms of cancer metastasis
- Calpain Protease Function and Regulation
- Fatty Acid Research and Health
- RNA modifications and cancer
- Drug-Induced Hepatotoxicity and Protection
- Diet, Metabolism, and Disease
- Epigenetics and DNA Methylation
- IL-33, ST2, and ILC Pathways
- Immune Cell Function and Interaction
Albert Einstein College of Medicine
2015-2024
Uttaranchal University
2021-2024
University of California, Los Angeles
2023-2024
Yeshiva University
2015-2020
Diabetes Research Center
2010-2020
Newcastle University
2016
Newcastle Hospitals - Campus for Ageing and Vitality
2016
The Bronx Defenders
2012-2014
Institute on Aging
2014
The relative balance between the quantity of white and brown adipose tissue can profoundly affect lipid storage whole-body energy homeostasis. However, mechanisms regulating formation, expansion, interconversion these 2 distinct types fat remain unknown. Recently, lysosomal degradative pathway macroautophagy has been identified as a regulator cellular differentiation, suggesting that autophagy may modulate this process in adipocytes. function differentiation was therefore examined current...
Lipid droplets (LDs), initially considered “inert” lipid deposits, have gained during the last decade classification of cytosolic organelles due to their defined composition and multiplicity specific cellular functions in which they are involved. The LD as brings along need for regulated turnover recent findings support direct contribution autophagy this through a process now described lipophagy. This paper focuses on characteristics new type selective consequences mobilization intracellular...
Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and varying degrees of necroinflammation. Although chronic oxidative stress, inflammatory cytokines, insulin resistance have been implicated in the pathogenesis NAFLD, mechanisms that underlie initiation progression this remain unknown. c-Jun N-terminal kinase (JNK) activated oxidants cytokines regulates hepatocellular injury resistance, suggesting may mediate development steatohepatitis. The presence function JNK...
SummaryMacroautophagy is a lysosomal degradative pathway that maintains cellular homeostasis by turning over components. Here we demonstrate role for autophagy in hypothalamic agouti-related peptide (AgRP) neurons the regulation of food intake and energy balance. We show starvation-induced mobilizes neuron-intrinsic lipids to generate endogenous free fatty acids, which turn regulate AgRP levels. The functional consequences inhibiting are failure upregulate response starvation, constitutive...
A single hematopoietic stem cell (HSC) is capable of reconstituting hematopoiesis and maintaining homeostasis by balancing self-renewal differentiation. The mechanisms HSC division balance, however, are not yet defined. Here we demonstrate, characterizing at the single-cell level a purified minimally heterogeneous murine Tie2+ population, that these top hierarchical HSCs preferentially undergo symmetric divisions. induction mitophagy, quality control process in mitochondria, plays an...
Abstract Macroautophagy is a highly conserved mechanism of lysosomal-mediated protein degradation that plays key role in maintaining cellular homeostasis by recycling amino acids, reducing the amount damaged proteins, and regulating levels response to extracellular signals. We have found macroautophagy induced after effector T cell activation. Engagement TCR CD28 results enhanced microtubule-associated 1 light chain 3 (LC3) processing, increased numbers LC3-containing vesicles, LC3 flux,...
Abstract Autophagy is a conserved pathway that maintains cellular quality control. Extracellular signal-regulated kinase (ERK) controls various aspects of cell physiology including proliferation. Multiple signalling cascades, ERK, have been shown to regulate autophagy, however whether autophagy proteins (ATG) unknown. Here we show growth factor exposure increases the interaction ERK cascade components with ATG in cytosol and nucleus. its upstream MEK localize extra-luminal face...
Activation of c-Jun N-terminal kinase (JNK) has been implicated as a mechanism in the development steatohepatitis. This finding, together with reported role JNK signaling obesity and insulin resistance, two components metabolic syndrome predisposing factors for fatty liver disease, suggests that may be central mediator an important therapeutic target To define isoform-specific functions steatohepatitis associated effects JNK1 or JNK2 ablation were determined developing established induced by...
<i>In vitro</i> studies of hepatocytes have implicated over-activation c-Jun N-terminal kinase (JNK) signaling as a mechanism tumor necrosis factor-α (TNF)-induced apoptosis. However, the functional significance JNK activation and role specific isoforms in TNF-induced hepatic apoptosis <i>in vivo</i> remain unclear. JNK1 JNK2 function was, therefore, investigated TNF-dependent, galactosamine/lipopolysaccharide (GalN/LPS) model liver injury. The toxin GalN converted LPS-induced from transient...
Insulin resistance and increased cytochrome P450 2E1 (CYP2E1) expression are both associated with mechanistically implicated in the development of nonalcoholic fatty liver disease. Although currently viewed as distinct factors, insulin CYP2E1 may be interrelated through ability CYP2E1-induced oxidant stress to impair hepatic signaling. To test this possibility, effects vitro vivo overexpression on hepatocyte signaling were examined. a cell line decreased tyrosine phosphorylation receptor...
MAF1 is a global repressor of RNA polymerase III transcription that regulates the expression highly abundant noncoding RNAs in response to nutrient availability and cellular stress. Thus, function thought be important for metabolic economy. Here we show whole-body knockout Maf1 mice confers resistance diet-induced obesity nonalcoholic fatty liver disease by reducing food intake increasing inefficiency. Energy expenditure −/− increased several mechanisms. Precursor tRNA synthesis was multiple...
Epidemiological and clinical studies have long shown that exposure to high levels of heavy metals are associated with increased risks neurodegenerative diseases. It is widely accepted autophagic dysfunction involved in pathogenesis various disorders; however, the role regulation macroautophagy/autophagy unclear. Here, we show manganese (Mn) induces a decline nuclear localization TFEB (transcription factor EB), master regulator autophagy-lysosome pathway, leading astrocytes mouse striatum. We...
Abstract Macroautophagy (hereafter referred to as autophagy) is a degradation pathway that delivers cytoplasmic materials lysosomes via double‐membraned vesicles designated autophagosomes. Cytoplasmic constituents are sequestered into autophagosomes, which subsequently fuse with lysosomes, where the cargo degraded. Autophagy crucial mechanism involved in many aspects of cell function, including cellular metabolism and energy balance; alterations autophagy have been linked various human...
Significance Cardiovascular diseases remain the leading cause of death worldwide, with atherosclerosis being most common source clinical events. Metabolic changes aging associate concurrent increased risk both type 2 diabetes and cardiovascular disease, former further raising latter. The activity a selective autophagy, chaperone-mediated autophagy (CMA), decreases age or upon dietary excesses. Here we study whether reduced CMA increases in mouse models. We have identified that is...