- Mitochondrial Function and Pathology
- Cardiac Ischemia and Reperfusion
- ATP Synthase and ATPases Research
- Spectroscopy Techniques in Biomedical and Chemical Research
- Glycosylation and Glycoproteins Research
- Galectins and Cancer Biology
- Viral Infections and Immunology Research
- Metabolism and Genetic Disorders
- CRISPR and Genetic Engineering
- Photoreceptor and optogenetics research
- Neurological diseases and metabolism
- COVID-19 Clinical Research Studies
- Receptor Mechanisms and Signaling
- Long-Term Effects of COVID-19
- RNA regulation and disease
- Phosphodiesterase function and regulation
- Nitric Oxide and Endothelin Effects
- Coenzyme Q10 studies and effects
- Glutathione Transferases and Polymorphisms
- Genetics, Aging, and Longevity in Model Organisms
- Frailty in Older Adults
- Metabolomics and Mass Spectrometry Studies
- Biochemical and Molecular Research
- Optical Imaging and Spectroscopy Techniques
- MicroRNA in disease regulation
Johns Hopkins University
2017-2024
Johns Hopkins Medicine
2017-2024
Emory University Hospital
2021
Sree Balaji Dental College and Hospital
2020
Ashok Leyland (India)
2017
Newcastle University
2012-2014
Buck Institute for Research on Aging
2011-2014
Wellcome Centre for Mitochondrial Research
2013
Recently developed technologies have enabled multi-well measurement of O(2) consumption, facilitating the rate mitochondrial research, particularly regarding mechanism action drugs and proteins that modulate metabolism. Among these technologies, Seahorse XF24 Analyzer was designed for use with intact cells attached in a monolayer to tissue culture plate. In order high throughput assay system which both energy demand substrate availability can be tightly controlled, we protocol expand...
Mitochondrial sn-glycerol 3-phosphate dehydrogenase (mGPDH) is a ubiquinone-linked enzyme in the mitochondrial inner membrane best characterized as part of glycerol phosphate shuttle that transfers reducing equivalents from cytosolic NADH into electron transport chain. Despite widespread expression mGPDH and availability mGPDH-null mice, physiological role this remains poorly defined many tissues, likely because compensatory pathways for regeneration NAD⁺ mechanisms metabolism. Here we...
Physiologic Ca
Central obesity with cardiometabolic syndrome (CMS) is a major global contributor to human disease, and effective therapies are needed. Here, we show that cyclic GMP-selective phosphodiesterase 9A inhibition (PDE9-I) in both male ovariectomized female mice suppresses preestablished severe diet-induced obesity/CMS or without superimposed mild cardiac pressure load. PDE9-I reduces total body, inguinal, hepatic, myocardial fat; stimulates mitochondrial activity brown white improves CMS,...
Neurodegeneration with brain iron accumulation is clinically and genetically heterogeneous because of mutations in at least 7 nuclear genes.We performed homozygosity mapping whole-exome sequencing 2 brothers from a consanguineous family.We identified homozygous missense mutation both the very recently chromosome 19 open-reading frame 12 gene. The disease presented before age 10 slowly progressive tremor, dystonia, spasticity. Additional features were optic atrophy, peripheral neuropathy,...
Background: Cardiac risk rises during acute SARS-CoV-2 infection and in long COVID syndrome humans, but the mechanisms behind COVID-19-linked arrhythmias are unknown. This study explores term effects of on cardiac conduction system (CCS) a hamster model COVID-19. Methods: Radiotelemetry conscious animals was used to non-invasively record electrocardiograms subpleural pressures after intranasal infection. cytokines, interferon-stimulated gene expression, macrophage infiltration CCS, were...
Inherited genetic variation of mitochondrial DNA (mtDNA) could account for the missing heritability human longevity and healthy aging. Here, we show no robust association between common variants mtDNA frailty (an "unhealthy aging" phenotype) or mortality in 700, more than 85-year-old, participants Newcastle 85+ study. Conflicting data from different populations underscore our conclusion that there is currently compelling link inherited
Reliable and valid biomarkers of ageing (BoA) are needed to understand mechanisms, test interventions predict the timing adverse health events associated with ageing. Since increased reactive oxygen species (ROS) production mitochondrial dysfunction consequences cellular senescence may contribute causally organisms, we focused on these parameters as candidate BoA. Superoxide levels, mass membrane potential in human peripheral blood mononuclear cells (PBMCs) subpopulations (lymphocytes...
ABSTRACT Central obesity with cardiometabolic syndrome (CMS) is a major global contributor to human disease, and effective therapies are needed. Here, we show inhibiting cyclic-GMP selective phosphodiesterase-9A (PDE9-I) suppresses established diet-induced CMS in ovariectomized female male mice. PDE9-I reduces abdominal, hepatic, myocardial fat accumulation, stimulates mitochondrial activity brown white fat, improves CMS, without altering or food intake. PDE9 localizes mitochondria, its...
Ca 2+ entry via the Mitochondrial Calcium Uniporter (MCU) participates in energetic adaption to workload under physiological conditions but is thought contribute cell death during ischemia-reperfusion (I/R) injury. We have previously shown that mitochondrial membrane potential (ΔΨm) instability contributes early-reperfusion arrhythmias and contractile dysfunction; however, role of (mCa ) uptake triggering ΔΨm oscillation unclear. Here, by acutely knocking out MCU, we examine whether...
Gastrulation, primary neurulation and secondary are the stages of spinal cord development.Spinal dysraphisms caused due to aberration in stages.Lipomyelocele is an occult dysraphism with estimated incidence 3.1 cases per 10,000 people.arly detection prompt neurosurgical intervention mandatory, for which neuroimaging plays a critical role.Here: we present rare case lipomyelocele pilonidal sinus.
acidosis and in long standing diabetes are additional complications which include micro vascular, macro vascular neuropathic diseases.Despite the tremendous value of self monitoring blood glucose for treatment diabetes, many patients find testing onerous some refuse to perform measurement.These complaints largely justified because is painful, inconvenient, messy, embarrassing above all expensive.Non invasive has been particular interest pain associated with monitoring.Ease use reduction can...
The regulated and reversible modification of Ser/Thr residues by O-linked N-Acetylglucosamine (O-GlcNAc) is termed O-GlcNAcylation. O-GlcNAc cycling on off proteins two conserved enzymes, the ‘writer’ Transferase (OGT) ‘eraser’ O-GlcNAcase (OGA). Crucially, O-GlcNAcylation implicated in nutrient sensing, cell growth stress adaptation. Despite these significant roles, precise pathways impacted what key substrate are involved remain incompletely understood. A hallmark cardiomyocyte hypertrophy...
Introduction: Acute and long-term cardiovascular complications of COVID-19 have been reported, ranging from arrhythmias, ischemic heart disease, failure to cerebrovascular cardiometabolic disorders, yet the underlying molecular mechanisms are not well understood. Here, we examine effects stimulating double-stranded RNA (dsRNA) pattern recognition receptor pathway, which is strongly induced activate interferon-stimulated gene (ISG) expression in during COVID-19, on excitation-contraction...
Intro: Cardiac risk rises during acute SARS-CoV-2 infection and in long COVID syndrome, but the mechanisms behind COVID-19-linked arrhythmias are unknown. Here, we test hypothesis that innate immune activation mitochondrial ROS contribute to cardiac conduction abnormalities pulmonary dysfunction a COVID-19 hamster model. Results: ECGs subpleural pressures were recorded by radiotelemetry over 4-week timespan after infection. Multiple observed, including bradycardia, sinus pauses,...