- Adipose Tissue and Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Diet and metabolism studies
- Birth, Development, and Health
- Protein Kinase Regulation and GTPase Signaling
- Pancreatic function and diabetes
- Bioinformatics and Genomic Networks
- Muscle metabolism and nutrition
- Peroxisome Proliferator-Activated Receptors
- Genetic Associations and Epidemiology
- Diabetes and associated disorders
- Genetics and Physical Performance
- Endoplasmic Reticulum Stress and Disease
- Cardiovascular Disease and Adiposity
- Lipid metabolism and biosynthesis
- Epigenetics and DNA Methylation
- Metabolism and Genetic Disorders
- Mitochondrial Function and Pathology
- Atomic and Molecular Physics
- Diet, Metabolism, and Disease
- Cancer, Hypoxia, and Metabolism
- Glycosylation and Glycoproteins Research
- Fatty Acid Research and Health
- Liver Disease Diagnosis and Treatment
- RNA modifications and cancer
Louisiana State University
2016-2025
Pennington Biomedical Research Center
2016-2025
Duke-NUS Medical School
2015-2024
Institute of Post Graduate Medical Education and Research
2016-2024
National University of Singapore
2014-2024
Signature Research (United States)
2023
Diabetes Care & Hormone Clinic
2022
Dr. Kovil's Diabetes Care Centre
2022
Pondicherry Institute of Medical Sciences
2022
Creative Commons
2022
Previous studies demonstrated that the cysteine-rich amino-terminal domain of Raf-1 kinase interacts selectively with phosphatidylserine (Ghosh, S., Xie, W. Q., Quest, A. F. G., Mabrouk, G. M., Strum, J. C., and Bell, R. M.(1994) Biol. Chem. 269, 10000-10007). Further analysis showed full-length bound to both phosphatidic acid (PA). Specifically, a carboxyl-terminal (RafC; residues 295-648 human Raf-1) interacted strongly acid. The binding RafC PA displayed positive cooperativity Hill...
Bladder cancer with loss of KDM6A expression is vulnerable to inhibition EZH2.
The gut microbiota evolves as the host ages, yet effects of these microbial changes on physiology and energy homeostasis are poorly understood. To investigate potential effects, we transplanted old or young mice into germ-free recipient mice. Both groups showed similar weight gain skeletal muscle mass, but receiving a transplant from donor unexpectedly increased neurogenesis in hippocampus brain intestinal growth. Metagenomic analysis revealed age-sensitive enrichment butyrate-producing...
A key event for Ras transformation involves the direct physical association between and Raf-1 kinase. This interaction promotes both Raf translocation to plasma membrane activation of kinase activity. Although substantial experimental evidence has demonstrated that residues 51-131 alone are sufficient binding, conflicting observations have suggested cysteine-rich domain (residues 139-184) may also be important with Ras. To clarify role in Ras-Raf we compared ability two distinct fragments...
Different domains of the serine/threonine kinase, raf-1, were expressed as fusion proteins with glutathione S-transferase (GST) in Escherichia coli and purified to near homogeneity by affinity chromatography. A cysteine-rich domain raf-1 was found contain 2 mol zinc (molar basis), similar analogous protein kinase C. GST-fusion proteins, containing bound liposomes a phosphatidylserine-dependent manner. In contrast C, translocation not dependent upon diacylglycerol, phorbol ester, or calcium,...
The Raf-1 protein kinase is the best-characterized downstream effector of activated Ras. Interaction with Ras leads to activation and results in transduction cell growth differentiation signals. details are unclear, but our characterization a second Ras-binding site cysteine-rich domain (CRD) involvement both sites effective Raf-1-mediated transformation provides insight into molecular aspects consequences Ras-Raf interactions. CRD member an emerging family domains, many which found within...
Rosiglitazone was found to simulate mitochondrial biogenesis in mouse brain an apolipoprotein (Apo) E isozyme-independent manner. induced both DNA (mtDNA) and estrogen-stimulated related receptor alpha (ESRRA) mRNA, a key regulator of biogenesis. Transcriptomics proteomics analysis suggested the mitochondria produced presence human ApoE3 E4 were not as metabolically efficient those wild type or ApoE knockout mice. Thus, we propose that PPARgamma agonism induces neuronal improves glucose...
There are strong genetic components to cardiorespiratory fitness and its response exercise training. It would be useful understand the differences in genomic profile of highly trained endurance athletes world class caliber sedentary controls. An international consortium (GAMES) was established order compare elite ethnicity-matched controls a case-control study design. Genome-wide association studies were undertaken on two cohorts (GENATHLETE Japanese runners), from which panel 45 promising...
Abstract Doxorubicin is a highly efficacious anti-cancer drug but causes cardiotoxicity in many patients. The mechanisms of doxorubicin-induced (DIC) remain incompletely understood. We investigated the characteristics and molecular DIC human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs). found that doxorubicin dose-dependent increases apoptotic necrotic cell death, reactive oxygen species production, mitochondrial dysfunction increased intracellular calcium concentration....
Aging is associated with alterations in glucose metabolism and sarcopenia that jointly contribute to a higher risk of developing type 2 diabetes. Because aging considered as state low-grade inflammation, this study we examined whether older, healthy (lean, community-dwelling) participants have altered signaling flux through toll-like receptor 4 (TLR4), key mediator innate adaptive immune responses. We also 4-month aerobic exercise program would an anti-inflammatory effect by reducing TLR4...
Eye photoreceptor membrane discs in outer rod segments are highly enriched the visual pigment rhodopsin and ω-3 fatty acid docosahexaenoic (DHA). The eye acquires DHA from blood, but transporters for uptake across blood-retinal barrier or retinal epithelium have not been identified. Mfsd2a is a newly described sodium-dependent lysophosphatidylcholine (LPC) symporter expressed at blood-brain that transports LPCs containing other long-chain acids. LPC transport via has shown to be necessary...
Adverse cardiac remodeling after myocardial infarction (MI) causes structural and functional changes in the heart leading to failure. The initial post-MI pro-inflammatory response followed by reparative or anti-inflammatory is essential for minimizing damage, healing, scar formation. Bone marrow-derived macrophages (BMDMs) are recruited injured myocardium repair as they can adopt both phenotypes modulate inflammatory responses, respectively. Yes-associated protein (YAP) transcriptional...
Thyroid hormone receptor β1 (THRB1) and estrogen-related α (ESRRA; also known as ERRα) both play important roles in mitochondrial activity. To understand their potential interactions, we performed transcriptome ChIP-seq analyses found that many genes were co-regulated by THRB1 ESRRA involved metabolic pathways. These included oxidative phosphorylation (OXPHOS), the tricarboxylic acid (TCA) cycle, β-oxidation of fatty acids. TH increased expression activity a THRB1-dependent manner through...
Dietary methionine restriction (MR) produces an integrated series of biochemical and physiological responses that improve biomarkers metabolic health, limit fat accretion, enhance insulin sensitivity. Using transcriptional profiling to guide tissue-specific evaluations molecular MR, we report liver adipose tissue are the primary targets a program remodeled lipid metabolism in each tissue. The MR diet produced coordinated downregulation lipogenic genes liver, resulting corresponding reduction...
Brown adipose tissue (BAT) is specialized to burn lipids for heat generation as a natural defense against cold and obesity. Previous studies established microRNAs (miRNAs) essential regulators of brown adipocyte differentiation, but whether miRNAs are required the feature maintenance mature adipocytes remains unknown. To address this question, we ablated Dgcr8, key regulator miRNA biogenesis pathway, in well white adipocytes. Adipose tissue-specific Dgcr8 knockout mice displayed enlarged...
The available data concerning oxidant stress and antioxidant capacity in hypothyroidism are scanty inconclusive. While some authors suggest that tissues may be protected from damage because of a hypometabolic state hypothyroidism, others report increased oxidative hypothyroidism. Selenium acts as cofactor for the thyroid hormone (TH) deiodinases activate then deactivate various THs their metabolites. inhibit autoimmunity.The study was designed, first, to impact patients primary due...
Brain development requires a massive increase in brain lipogenesis and accretion of the essential omega-3 fatty acid docosahexaenoic (DHA). acquisition DHA is primarily mediated by transporter Major Facilitator Superfamily Domain containing 2a (Mfsd2a) expressed endothelium blood-brain barrier (BBB) other abundant cell types within brain. Mfsd2a transports polyunsaturated acids (PUFAs) esterified to lysophosphatidylcholine (LPC-DHA). However, function incompletely understood. Here, we...
Fatty acids are the primary fuel source for skeletal muscle during most of our daily activities, and impaired fatty acid oxidation (FAO) is associated with insulin resistance. We have developed a mouse model FAO by deleting carnitine palmitoyltransferase-1b specifically in (Cpt1b(m-/-)). Cpt1b(m-/-) mice increased glucose utilization resistant to diet-induced obesity. Here, we show that inhibition mitochondrial induces FGF21 expression muscle. The induction Cpt1b-deficient dependent on AMPK...