A5052529804- Neuroinflammation and Neurodegeneration Mechanisms
- Adipose Tissue and Metabolism
- Neuroscience and Neuropharmacology Research
- RNA modifications and cancer
- Neurotransmitter Receptor Influence on Behavior
- RNA Research and Splicing
- Neurological Disease Mechanisms and Treatments
- MicroRNA in disease regulation
- Neurogenesis and neuroplasticity mechanisms
- Genetics, Aging, and Longevity in Model Organisms
- Immune cells in cancer
- Mitochondrial Function and Pathology
- Telomeres, Telomerase, and Senescence
- Single-cell and spatial transcriptomics
- Epigenetics and DNA Methylation
- Peroxisome Proliferator-Activated Receptors
- Receptor Mechanisms and Signaling
- Sirtuins and Resveratrol in Medicine
- Extracellular vesicles in disease
- RNA and protein synthesis mechanisms
- NF-κB Signaling Pathways
- Nerve injury and regeneration
- T-cell and B-cell Immunology
- Barrier Structure and Function Studies
- PI3K/AKT/mTOR signaling in cancer
National Institute on Aging
2016-2025
National Institutes of Health
2015-2024
Institute on Aging
2015-2024
ORCID
2021
Center for Information Technology
2015
Duke University Hospital
2015
Duke Medical Center
2015
Ralph H. Johnson VA Medical Center
2015
Medical University of South Carolina
2015
National Cancer Institute
2012
Sirt1 is an NAD+-dependent deacetylase that extends lifespan in lower organisms and improves metabolism delays the onset of age-related diseases mammals. Here we show SRT1720, a synthetic compound was identified for its ability to activate vitro, both mean maximum adult mice fed high-fat diet. This extension accompanied by health benefits including reduced liver steatosis, increased insulin sensitivity, enhanced locomotor activity normalization gene expression profiles markers inflammation...
Inflammation is a common component of acute injuries the central nervous system (CNS) such as ischemia, and degenerative disorders Alzheimer's disease. Glial cells play important roles in local CNS inflammation, an understanding for microRNAs glial reactivity injury disease settings may therefore lead to development novel therapeutic interventions. Here, we show that miR‐181 family developmentally regulated present high amounts astrocytes compared neurons. Overexpression miR‐181c cultured...
Type 2 diabetes is a chronic age-associated degenerative metabolic disease that reflects relative insulin deficiency and resistance. Extracellular vesicles (EVs) (exosomes, microvesicles, apoptotic bodies) are small (30-400 nm) lipid-bound capable of shuttling functional proteins, nucleic acids, lipids as part intercellular communication systems. Recent studies in mouse models cell culture suggest EVs may modulate signaling. Here, we designed cross-sectional longitudinal cohorts euglycemic...
Summary Mitochondrial function in human skeletal muscle declines with age. Most evidence for this decline comes from studies that assessed mitochondrial indirectly, and the impact of such deterioration respect to physical has not been clearly delineated. We hypothesized respiration permeabilized fibers age correlates phosphocreatine postexercise recovery rate ( kPC r), performance, aerobic fitness. was by high‐resolution respirometry saponin‐permeabilized vastus lateralis biopsies 38...
Rationale: Multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis (EAE), are inflammatory disorders of the central nervous system (CNS). The function platelets in pathologies is thus far poorly defined. Objective: We addressed role mediating CNS inflammation EAE. Methods Results: found that were present human MS lesions as well mice subjected to EAE but not from control nondiseased mice. Platelet depletion at effector-inflammatory phase resulted significantly...
Abstract Aging is a major international concern that brings formidable socioeconomic and healthcare challenges. Small molecules capable of improving the health older individuals are being explored. enhance cellular stress resistance promising avenue to alleviate declines seen in human aging. Tomatidine, natural compound abundant unripe tomatoes, inhibits age-related skeletal muscle atrophy mice. Here we show tomatidine extends lifespan healthspan C. elegans , an animal model aging which...
Methamphetamine (METH) addiction is associated with several neuropsychiatric symptoms. Little known about the effects of METH on gene expression and epigenetic modifications in rat nucleus accumbens (NAC). Our study investigated a non-toxic injection (20 mg/kg) expression, histone acetylation, acetyltransferase (HAT), ATF2, deacetylases (HDACs), HDAC1 HDAC2, that structure. Microarray analyses done at 1, 8, 16 24 hrs after identified METH-induced changes genes previously implicated acute...
Recent evidence suggests that ovarian high-grade serous carcinoma (HGSC) originates from the epithelium of fallopian tube. However, most mouse models are based on previous prevailing view cancer develops transformation surface epithelium. Here, we report extensive histological and molecular characterization mogp-TAg transgenic mouse, which expresses SV40 large T-antigen (TAg) under control müllerian-specific Ovgp-1 promoter. Histological analysis tubes mice identified a variety neoplastic...
Cells responding to DNA damage implement complex adaptive programs that often culminate in one of two distinct outcomes: apoptosis or senescence. To systematically identify factors driving each response, we analyzed human IMR-90 fibroblasts exposed increasing doses the genotoxin etoposide and identified SRC as a key kinase contributing early this dichotomous decision. was activated by low but not high levels etoposide. With damage, SRC-mediated activation p38 critically promoted expression...
The potentially neurotrophic cytokine transforming growth factor-beta1 (TGF-beta1) is locally expressed following human stroke and experimental ischemic lesions, but the cellular source(s) profile of induction have so far not been established in focal cerebral ischemia. This study presents time course a localization TGF-beta1 mRNA, visualized by situ hybridization combined with immunohistochemical staining for microglia, macrophages, or astrocytes, on brain sections from adult spontaneously...
Transient middle cerebral artery occlusion in rats leads to infarction of the lateral part striatum and adjacent neocortex, with selective neuronal necrosis bordering penumbral zones. Administration glutamate, cytokine, leukocyte antagonists have rescued mainly neocortical neurons, indicating differences degenerative processes. The aim this study was, therefore, describe microglial/macrophage activation polymorphonuclear recruitment patterns correlate these ischemia-induced analysis showed...
Approximately 35 million people worldwide suffer from Alzheimer's disease (AD). Existing therapeutics, while moderately effective, are currently unable to stem the widespread rise in AD prevalence. is associated with an increase amyloid beta (Aβ) oligomers and hyperphosphorylated tau, along cognitive impairment neurodegeneration. Several antidepressants have shown promise improving cognition alleviating oxidative stress but failed as long-term therapeutics. In this study, amitriptyline,...
Breast cancer cells facilitate distant metastasis through the induction of immunosuppressive regulatory B cells, designated tBregs. We report in this study that, to do this, breast produce metabolites 5-lipoxygenase pathway such as leukotriene B4 activate peroxisome proliferator-activated receptor α (PPARα) cells. Inactivation signaling or genetic deficiency PPARα blocks generation tBregs and thereby abrogates lung mice with established cancer. Thus, addition eliciting fatty acid oxidation...
We have previously shown that Wnt5A drives invasion in melanoma. also promotes resistance to therapy designed target the BRAF(V600E) mutation Here, we show melanomas characterized by high levels of respond therapeutic stress increasing p21 and expressing classical markers senescence, including positivity for senescence-associated β-galactosidase (SA-β-gal), heterochromatic foci (SAHF), H3K9Me chromatin marks, PML bodies. find despite this, these cells retain their ability migrate invade....
Abstract The phosphorylation of eIF4E1 at serine 209 by MNK1 or MNK2 has been shown to initiate oncogenic mRNA translation, a process that favours cancer development and maintenance. Here, we interrogate the MNK-eIF4E axis in diffuse large B-cell lymphoma (DLBCL) show distinct distribution germinal centre (GCB) activated (ABC) DLBCL. Despite displaying differential GCB ABC, both MNKs functionally complement each other sustain cell survival. MNK inhibition ablates concurrently enhances eIF4E3...
The Human antigen R protein (HuR) is an RNA-binding that recognizes U/AU-rich elements in diverse RNAs through two RNA-recognition motifs, RRM1 and RRM2, post-transcriptionally regulates the fate of target RNAs. natural product dihydrotanshinone-I (DHTS) prevents association HuR vitro cultured cells by interfering with binding to RNA. Here, we report structural determinants interaction between DHTS impact on mRNAs transcriptome-wide. NMR titration Molecular Dynamics simulation identified...
Familial dysautonomia (FD) results from mutation in IKBKAP/ELP1, a gene encoding the scaffolding protein for Elongator complex. This highly conserved complex is required translation of codon-biased genes lower organisms. Here we investigate whether serves similar function mammalian peripheral neurons, population devastated FD. Using eGFP sensors, and multiplexing codon usage with transcriptome proteome analyses over 6,000 genes, identify two categories as well specific identities that depend...
Long non-coding RNAs (lncRNAs) regulate vital biological processes, including cell proliferation, differentiation and development. A subclass of lncRNAs is synthesized from microRNA (miRNA) host genes (MIRHGs) due to pre-miRNA processing, are categorized as miRNA-host gene (lnc-miRHGs). Presently, the cellular function most lnc-miRHGs not well understood. We demonstrate a miRNA-independent role for nuclear-enriched lnc-miRHG in cycle progression. MIR100HG produces spliced stable that display...
The cannabinoid 1 receptor (CB1R) regulates insulin sensitivity and glucose metabolism in peripheral tissues. CB1R is expressed on pancreatic beta cells coupled to the G protein Gαi, suggesting a negative regulation of endogenous signalling cell. Deciphering exact function has been confounded by expression this multiple tissues involved regulating metabolism. Thus, models global genetic or pharmacological blockade, it difficult distinguish indirect effects improved from direct inhibiting per...
Skeletal muscle contains long multinucleated and contractile structures known as fibers, which arise from the fusion of myoblasts into myotubes during myogenesis. The myogenic regulatory factor (MRF) MYF5 is earliest to be expressed myogenesis functions a transcription in progenitor cells (satellite cells) myocytes. In mouse C2C12 myocytes, implicated initial steps myoblast differentiation myotubes. Here, using ribonucleoprotein immunoprecipitation (RIP) analysis, we discovered novel...