A5106468855- Mitochondrial Function and Pathology
- Metabolism, Diabetes, and Cancer
- Adipose Tissue and Metabolism
- Drug Transport and Resistance Mechanisms
- Immune Cell Function and Interaction
- Cancer, Hypoxia, and Metabolism
- Histone Deacetylase Inhibitors Research
- Amyotrophic Lateral Sclerosis Research
- Ubiquitin and proteasome pathways
- Epigenetics and DNA Methylation
- Metabolism and Genetic Disorders
- Cholesterol and Lipid Metabolism
- Peroxisome Proliferator-Activated Receptors
- Telomeres, Telomerase, and Senescence
- ATP Synthase and ATPases Research
- Synthesis of Indole Derivatives
- Redox biology and oxidative stress
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Hippo pathway signaling and YAP/TAZ
- Spectroscopy Techniques in Biomedical and Chemical Research
- Melanoma and MAPK Pathways
- Sirtuins and Resveratrol in Medicine
- Neurogenetic and Muscular Disorders Research
- Genetic Syndromes and Imprinting
- Calcium signaling and nucleotide metabolism
Houston Methodist
2013-2024
BioEnergetics (United States)
2017-2024
Cornell University
2011-2023
Methodist Hospital
2012-2023
Weill Cornell Medicine
2021-2023
Texas Medical Center
2022
Huntington Medical Research Institutes
2022
Baylor College of Medicine
2021
Chinese PLA General Hospital
2017
Methodist Hospital
2013
Abstract Altered metabolism in cancer cells is suspected to contribute chemoresistance, but the precise mechanisms are unclear. Here, we show that intracellular ATP levels a core determinant development of acquired cross-drug resistance human colon harbor different genetic backgrounds. Drug-resistant were characterized by defective mitochondrial production, elevated aerobic glycolysis, higher absolute ATP, and enhanced HIF-1α–mediated signaling. Interestingly, direct delivery into...
Abstract This study establishes the physiological role of Fused in Sarcoma (FUS) mitochondrial DNA (mtDNA) repair and highlights its implications to pathogenesis FUS-associated neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Endogenous FUS interacts with recruits mtDNA Ligase IIIα (mtLig3) damage sites within mitochondria, a relationship essential for maintaining integrity healthy cells. Using ALS patient-derived mutant cell lines, transgenic mouse model, human...
Extensive reprogramming of cellular energy metabolism is a hallmark cancer. Despite its importance, the molecular mechanism controlling this tumour metabolic shift remains not fully understood. Here we show that 14-3-3σ regulates cancer and protects cells from tumorigenic transformation. opposes tumour-promoting programmes by enhancing c-Myc poly-ubiquitination subsequent degradation. demonstrates suppressive impact on glycolysis, glutaminolysis, mitochondrial biogenesis other major...
Abstract Aberrant mitochondrial energy transfer underlies prevalent chronic health conditions, including cancer, cardiovascular, and neurodegenerative diseases. Mitochondrial transplantation represents an innovative strategy aimed at restoring favorable metabolic phenotypes in cells with dysfunctional metabolism. While promising, significant barriers to vivo translation of this approach abound, limited cellular uptake recognition mitochondria as foreign. The objective is functionalize...
ERK5 (extracellular signal-regulated kinase 5) is a dual transcription factor containing an N-terminal domain and C-terminal transcriptional activation domain. Many inhibitors have been developed tested to treat cancer inflammatory diseases. However, recent data raised questions about the role of catalytic activity in proliferation inflammation. We aimed investigate how reprograms myeloid cells proinflammatory senescent phenotype, subsequently leading atherosclerosis. A S496A...
Sirtuin 1 (SIRT1) NAD+-dependent deacetylase regulates energy metabolism by modulating expression of genes involved in gluconeogenesis and other liver fasting responses. While many effects SIRT1 on gene are mediated deacetylation activation peroxisome proliferator activated receptor coactivator α (PGC-1α), also binds directly to DNA bound transcription factors, including nuclear receptors (NRs), modulate their activity. Since thyroid hormone β1 (TRβ1) several target interacts with PGC-1α, we...
Heart disease remains the leading cause of death worldwide, highlighting a pressing need to identify novel regulators cardiomyocyte (CM) function that could be therapeutically targeted. The mammalian Hippo/Tead pathway is critical in embryonic cardiac development and perinatal CM proliferation. However, requirement Tead1, transcriptional effector this pathway, adult heart unknown. Here, we show tamoxifen-inducible CM-specific Tead1 ablation led lethal acute-onset dilated cardiomyopathy,...
Abstract BACKGROUND: Mutations in the tumor protein 53 ( TP53 ) suppressor gene are common head and neck squamous cell carcinoma (HNSCC) correlate with radioresistance. Currently, there no clinically available therapeutic approaches targeting p53 HNSCC. In this report, authors propose a strategy that uses mutational status to individualize antimetabolic strategies for potentiation of radiation toxicity HNSCC cells. METHODS: Glycolytic flux mitochondrial respiration were evaluated wild‐type...
Nuclear receptors (NRs) play crucial roles in the regulation of hepatic cholesterol synthesis, metabolism, and conversion to bile acids, but their actions cholangiocytes have not been examined. In this study, we investigated NRs cholangiocyte physiology metabolism flux. We examined expression other genes involved homeostasis freshly isolated cultured murine found that these cells express a specific subset NRs, including liver X receptor (LXR) β peroxisome proliferator-activated (PPAR) δ....
Biological processes require close cooperation of multiple transcription factors that integrate different signals. Thyroid hormone receptors (TRs) induce Krüppel-like factor 9 (KLF9) to regulate neurogenesis. Here, we show triiodothyronine (T3) also works through TR KLF9 in HepG2 liver cells, mouse liver, and human primary hepatocytes sought understand TR/KLF9 network function the hepatocyte lineage stem cells. Knockdown experiments reveal regulates hundreds target genes modulates T3...
New approaches to treat ovarian cancer, the fifth leading cause of cancer mortality among women, are being sought, with targeting epigenetic modulators now receiving much attention. The histone acetyltransferase HBO1 functions in regulating diverse molecular processes, including DNA repair, transcription and replication, is highly expressed primary cancer. Here we define both function a role cell biomechanics for preferentially acetylates H4 through concomitant overexpression co-regulator...
The incidence of cardiovascular disease (CVD) is higher in cancer survivors than the general population. Several treatments are recognized as risk factors for CVD, but specific therapies unavailable. Many activate shared signaling events, which reprogram myeloid cells (MCs) towards persistent senescence-associated secretory phenotype (SASP) and consequently exact mechanisms remain unclear. This study aimed to provide mechanistic insights potential by investigating how chemo-radiation can...
Fibroblast-to-myofibroblast transition (FMT) leads to excessive extracellular matrix (ECM) deposition—a well-known hallmark of fibrotic disease. Transforming growth factor-β (TGF-β) is the primary cytokine driving FMT, and this phenotypic conversion associated with mitochondrial dysfunction, notably a metabolic reprogramming towards enhanced glycolysis. The objective study was examine whether establishment favorable phenotypes in TGF-β-stimulated fibroblasts could attenuate FMT. hypothesis...
Metabolic, inflammatory, and functional changes occur in cardiovascular aging which may stem from oxidative stress be remediable with antioxidants. Glutathione, an intracellular antioxidant, declines aging, supplementation glutathione precursors, N-acetyl cysteine (NAC) glycine (Gly), increases tissue glutathione. Thirty-month old mice were fed diets supplemented NAC or NAC+Gly and, after 7 weeks, cardiac function molecular studies performed. The improved diastolic function, increasing peak...
FOXP3 is the lineage-defining transcription factor for Tregs, a cell type critical to immune tolerance, but mechanisms that control expression in Tregs remain incompletely defined, particularly as it relates signals downstream of TCR and CD28 signaling. Herein, we studied role IRF4 BATF3, two factors upregulated upon T activation, conversion conventional CD4+ cells FOXP3+ (iTregs) vitro. We found must partner with BATF3 bind regulatory region Foxp3 locus where they cooperatively repress...
CAG repeat expansion is the genetic cause of nine incurable polyglutamine (polyQ) diseases with neurodegenerative features. Silencing RNA holds great therapeutic value. Here, we developed a repeat-based RNA-cleaving DNAzyme that catalyzes destruction expanded six polyQ high potency. preferentially cleaved allele in spinocerebellar ataxia type 1 (SCA1) cells. While cleavage was non-allele-specific for 3 (SCA3) cells, treatment leads to improved cell viability without affecting mitochondrial...
Abstract The pro‐inflammatory microenvironment that contributes to atherosclerotic plaque progression is sustained by M1 macrophages. Metabolic reprogramming toward heightened glycolysis accompanies macrophage polarization, with approaches aimed at lessening glycolytic metabolism in macrophages standing impact disease progression. objective decrease the inflammatory response lesions inducing favorable metabolic phenotypes using an innovative mitochondrial transplantation strategy. hypothesis...
Limited by difficulties in early detection and availabilities of effective treatments, pancreatic cancer is a highly malignant disease with poor prognosis. Nuclear receptors are family ligand-dependent transcription factors that druggable therapeutic targets playing critical roles human physiological pathological development, including cancer. In this study, we explored the potential as well molecular mechanisms liver X receptor (LXR) agonist GW3965 Soft-agar colony formation assay,...
The transformation of prostatic epithelial cells to prostate cancer (PCa) has been characterized as a transition from citrate secretion oxidation, which one would anticipate enhanced mitochondrial complex I (CI) respiratory flux. Molecular mechanisms for this are attributed declining zinc concentrations. unique metabolic properties PCa have become hot research area. Several publications provided indirect evidence based on investigations using pre-clinical models, established cell lines, and...
Melanoma is one of the most malignant skin cancers that require comprehensive therapies, including chemotherapy. A plant-derived drug, plumbagin (PLB), exhibits an anticancer property in several cancers. We compared cytotoxic and metabolic roles PLB A375 SK-MEL-28 cells, each with different aggressiveness. In our results, they were observed to have distinctive mitochondrial respiratory functions. The primary reactive oxygen species (ROS) source can be robustly attenuated by cell membrane...