A5017868137- Adipose Tissue and Metabolism
- Exercise and Physiological Responses
- Muscle Physiology and Disorders
- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Angiogenesis and VEGF in Cancer
- Mitochondrial Function and Pathology
- Cardiomyopathy and Myosin Studies
- Autophagy in Disease and Therapy
- Thermoregulation and physiological responses
- Estrogen and related hormone effects
- Cardiovascular and exercise physiology
- Lymphatic System and Diseases
- Sirtuins and Resveratrol in Medicine
- Muscle metabolism and nutrition
- Calcium signaling and nucleotide metabolism
- ATP Synthase and ATPases Research
- Nitric Oxide and Endothelin Effects
- Genetic Neurodegenerative Diseases
- Adipokines, Inflammation, and Metabolic Diseases
- Metabolism, Diabetes, and Cancer
- Ion Transport and Channel Regulation
- Peripheral Artery Disease Management
- Muscle activation and electromyography studies
- Adenosine and Purinergic Signaling
University of Houston
2024
The University of Texas Health Science Center at Houston
2016-2023
Brown Foundation
2016-2023
The Ohio State University
2011-2021
Discovery Institute
2016
Sanford Burnham Prebys Medical Discovery Institute
2016
Sarcolipin (SLN) is a novel regulator of sarcoplasmic reticulum Ca2+ ATPase (SERCA) in muscle. SLN binding to SERCA uncouples transport from ATP hydrolysis. By this mechanism, promotes the futile cycling SERCA, contributing muscle heat production. We recently showed that plays an important role cold- and diet-induced thermogenesis. However, detailed mechanism how regulates metabolism remains unclear. In study, we used both knockout (Sln−/−) skeletal muscle-specific overexpression (SlnOE)...
IL-13 hits the gym Interleukin-13 (IL-13) is a cytokine secreted by T cells, innate lymphoid cells (ILC2s), and granulocytes. It acts as central mediator in allergy antihelminth defense with various effects. Knudsen et al. report distinct role for exercise metabolism (see Perspective Correia Ruas). Mice subjected to endurance training showed increases circulating IL-13, which correlated ILC2 expansion muscles. By contrast, exercise-induced muscle fatty acid utilization mitochondrial...
The utrophin-dystrophin deficient (DKO) mouse model has been widely used to understand the progression of Duchenne muscular dystrophy (DMD). However, it is unclear as what extent muscle pathology affects metabolism. Therefore, present study was focused on understanding energy expenditure in whole animal and isolated extensor digitorum longus (EDL) determine changes metabolic enzymes. Our results show that 8 week-old DKO mice consume higher oxygen relative activity levels. Interestingly EDL...
Sarcolipin (SLN) is a regulator of sarcoendoplasmic reticulum calcium ATPase in skeletal muscle. Recent studies using SLN-null mice have identified SLN as key player muscle thermogenesis and metabolism. In this study, we exploited overexpression ( Sln OE ) mouse model to determine whether increased level affected contractile properties, exercise capacity/fatigue, metabolic rate whole animals isolated We found that are more resistant fatigue can run significantly longer distances than...
Sarcolipin (SLN) is a regulator of sarco/endo plasmic reticulum Ca 2+ -ATPase (SERCA) pump and has been shown to be involved in muscle nonshivering thermogenesis (NST) energy metabolism. Interestingly, SLN expression significantly upregulated both during development several disease states. However, the significance altered patho-physiology not completely understood. We have previously that transgenic over-expression skeletal detrimental, can promote oxidative metabolism exercise capacity. In...
Skeletal muscle ischemia is a major consequence of peripheral arterial disease (PAD) or critical limb (CLI). Although therapeutic options for resolving in PAD/CLI are limited, the issue compounded by poor understanding mechanisms driving vascularization. We found that nuclear receptor estrogen-related alpha (ERRα) expression induced murine skeletal hindlimb (HLI), and cultured myotubes hypoxia, suggesting potential role ERRα ischemic response. To test this, we generated muscle-specific...
Background Peripheral arterial disease and critical limb ischemia are cardiovascular complications associated with vascular insufficiency, oxidative metabolic dysfunction, myopathy in the limbs. Estrogen-related receptor gamma (ERRγ) has emerged as a dual regulator of paracrine angiogenesis metabolism through transgenic mouse studies. Here our objective was to investigate whether postischemic intramuscular targeting ERRγ via gene therapy promotes ischemic recovery preclinical model...
Abstract Dissecting exercise-mimicking pathways that can replicate the benefits of exercise in obesity and diabetes may lead to promising treatments for metabolic disorders. Muscle estrogen-related receptor gamma (ERRγ) is induced by exercise, when over-expressed skeletal muscle mimics stimulating glycolytic-to-oxidative myofiber switch, mitochondrial biogenesis angiogenesis lean mice. The objective this study was test whether ERRγ obese mice mitigates weight gain insulin resistance. To do...
Abstract Transcriptional determinants in the skeletal muscle that govern exercise capacity, while poorly defined, could provide molecular insights into how improves fitness. Here, we have elucidated role of nuclear receptors, estrogen‐related receptor alpha and gamma (ERRα/γ) regulating myofibrillar composition, contractility, capacity muscle. We used muscle‐specific single or double (DKO) ERRα/γ knockout mice to investigate effect deletion on parameters. Individual did not a significant...
Obesity and type II diabetes are leading causes of peripheral arterial disease (PAD), which is characterized by vascular insufficiency ischemic damage in the limb skeletal muscle. Glycemic control not sufficient to prevent progression PAD, molecular targets that can promote muscle neo-angiogenesis obesity remain poorly defined. Here, we have investigated whether nuclear receptor estrogen-related alpha (ERRα) revascularization muscles diet-induced obese (DIO) mice. Using muscle-specific ERRα...
CASQ (calsequestrin) is a Ca2+-buffering protein localized in the muscle SR (sarcoplasmic reticulum); however, it unknown whether Ca2+ binding to CASQ2 due its location inside rich or preference for over other ions. Therefore major aim of present study was determine how selects metal ions by studying monomer folding and subsequent aggregation upon exposure alkali (monovalent), alkaline earth (divalent) transition (polyvalent) metals. We additionally investigated CPVT (catecholaminergic...
Estrogen-related receptors (ERRs) have emerged as major metabolic regulators in various tissues. However, their expression and function the vasculature remains unknown. Here, we report transcriptional program cellular of ERRα endothelial cells (ECs), a cell type with multifaceted role vasculature. Of three ERR subtypes, ECs exclusively express ERRα. Gene profiling lacking revealed that predominantly acts repressor, targeting genes linked angiogenesis, migration, adhesion. ERRα-deficient...
Skeletal muscle atrophy is a prevalent complication in multiple chronic diseases and disuse conditions. Fibroblast growth factor-inducible 14 (Fn14) member of the TNF receptor superfamily bona fide TWEAK cytokine. Accumulating evidence suggests that Fn14 levels are increased catabolic conditions as well during exercise. However, role regulation skeletal mass function remains poorly understood. In this study, through generation novel muscle-specific Fn14-knockout mice, we have investigated...
Skeletal muscle wasting is prevalent in many chronic diseases, necessitating inquiries into molecular regulation of mass. Nuclear receptor co-activator peroxisome proliferator-activated 1 alpha (PGC1α) and its splice variant PGC1α4 increase skeletal However, the effect other PGC1 sub-type, PGC1β, on size unclear. In transgenic mice selectively over-expressing PGC1β muscle, we have found that progressively decreases mass predominantly associated with loss type 2b fast-twitch myofibers....
Aryl Hydrocarbon Receptor Nuclear Translocator/ hypoxia-inducible factor 1 beta (ARNT/ HIF1β), a member of bHLH-PAS family transcriptional factors, plays critical role in metabolic homeostasis, insulin resistance and glucose intolerance. The contributions ARNT pancreas, liver adipose tissue to energy balance through gene regulation have been described. Surprisingly, the impact signaling skeletal muscles, one major organs involved disposal, has not investigated, especially type II diabetes....
Abstract Skeletal muscle is a highly plastic tissue that can alter its metabolic and contractile features, as well regenerative potential in response to exercise other conditions. Multiple signaling factors including metabolites, kinases, receptors, transcriptional have been studied the regulation of skeletal plasticity. Recently, estrogen-related receptors (ERRs) emerged critical hub control homeostasis. ERRα ERRγ – two expressed ERR sub-types respond various extracellular cues such...
We previously showed that complete loss of smooth muscle myosin heavy chain isoform 2 (SM2) resulted in postnatal lethality, but het mice a partial SM2 (SM2+/–) was accompanied by down-regulation SM1 with unaltered SM2:SM1 ratio. To determine whether normal bladder function would be maintained throughout its lifespan, we aged WT and SM2+/– up to 18 months analyzed a) ratio b) structure c) mice. A notable finding ~50% 15–18 old male exhibited urinary retention the distention upper urethra. In...
Autophagy is an essential self-degradative and recycling mechanism that maintains cellular homeostasis. Estrogen receptor-related orphan receptors (ERRs) are fundamental in regulating cardiac metabolism function. Previously, we showed ERR agonists improve function models of heart failure induce autophagy cardiomyocytes. Here, characterized a by which ERRs the pathway Transcription factor EB (TFEB) master regulator autophagy-lysosome has been shown to be important autophagy. We discovered...
Sarcolipin (SLN) is a transmembrane protein that interacts with Sarco(endo)plasmic Reticulum Calcium ATPase (SERCA) and expressed in cardiac skeletal muscle. SLN known to inhibit Vmax of SERCA, but its role muscle physiology yet be fully understood. We have shed some light on this front, by showing knock out (SLN KO) mice are highly sensitive acute cold prone develop obesity when fed high fat diet. Moreover, we showed the KO can rescued from hypothermia over expression transgene; suggesting...
Sarcolipin (SLN) is a novel regulator of S arco/ E ndoplasmic R eticulum C 2+ ‐ A TPase (SERCA) pump and it expressed exclusively in striated muscle. Recent in‐vitro studies suggested that SLN can increase heat production by uncoupling SERCA‐mediated ATP hydrolysis from Ca transport but its role muscle physiology has not been established. To demonstrate the basis for thermogenesis vivo , we challenged −/− mice to acute cold (4°C). Here show without interscapular Brown Adipose Tissue ( iBAT )...