A5040510768- Cardiac Valve Diseases and Treatments
- Metabolomics and Mass Spectrometry Studies
- Cardiac Structural Anomalies and Repair
- Adipose Tissue and Metabolism
- Pancreatic function and diabetes
- Liver Disease Diagnosis and Treatment
- Infective Endocarditis Diagnosis and Management
- Cassava research and cyanide
- Connective tissue disorders research
- Cardiovascular Function and Risk Factors
- Cardiac Fibrosis and Remodeling
- Congenital heart defects research
- Computational Drug Discovery Methods
- Cardiovascular and exercise physiology
- Diet and metabolism studies
- Fibroblast Growth Factor Research
- Metabolism and Genetic Disorders
- Cardiomyopathy and Myosin Studies
- Peptidase Inhibition and Analysis
- Metabolism, Diabetes, and Cancer
- Muscle metabolism and nutrition
- Cardiovascular Health and Risk Factors
- Dermatological and Skeletal Disorders
- Health, Environment, Cognitive Aging
- Diabetes and associated disorders
Medical University of South Carolina
2019-2025
Beth Israel Deaconess Medical Center
2017-2024
Pancreatic Cancer Action Network
2023
Broad Institute
2022
Cardiovascular Institute Hospital
2021
Harvard University
2017-2018
Somerville Hospital
2018
Massachusetts General Hospital
2016-2017
Purdue University West Lafayette
1976
Pharmacologic inhibition of the renal sodium/glucose cotransporter-2 induces glycosuria and reduces glycemia. Given that SGLT2 inhibitors (SGLT2i) reduce mortality cardiovascular risk in type 2 diabetes, improved understanding molecular mechanisms mediating these metabolic effects is required. Treatment obese but nondiabetic mice with SGLT2i canagliflozin (CANA) adiposity, improves glucose tolerance despite reduced plasma insulin, increases ketones, lipid profiles. Utilizing an integrated...
Unbiased, "nontargeted" metabolite profiling techniques hold considerable promise for biomarker and pathway discovery, in spite of the lack successful applications to human disease. By integrating nontargeted metabolomics, genetics, detailed phenotyping, we identified dimethylguanidino valeric acid (DMGV) as an independent CT-defined nonalcoholic fatty liver disease (NAFLD) offspring cohort Framingham Heart Study (FHS) participants. We verified relationship between DMGV early hepatic...
The relation between ventricular arrhythmia and fibrosis in mitral valve prolapse (MVP) is reported, but underlying valve-induced mechanisms remain unknown. We evaluated the association abnormal MVP-related mechanics myocardial fibrosis, their with arrhythmia.
Human pluripotent stem cell (hPSC)-derived cardiac therapies hold great promise for heart regeneration but face major translational barriers due to allogeneic immune rejection. Here, we engineered hypoimmunogenic hPSCs using a two-step CRISPR-Cas9 strategy: (1) B2M knockout, eliminating HLA class I surface expression, and (2) knock-in of HLA-E or HLA-G trimer constructs in the AAVS1 safe harbor locus confer robust evasion. Hypoimmunogenic maintained pluripotency, efficiently differentiated...
Background Mitral valve prolapse (MVP) is one of the most common forms cardiac disease and affects 2% to 3% population. Previous imaging reports have indicated that myocardial fibrosis in MVP described its association with sudden death. These data combined evidence for postrepair ventricular dysfunction surgical patients support a link between MVP. Methods Results We performed histopathologic analysis left (LV) biopsies from peripapillary regions, inferobasal LV wall apex on MVP, as well...
Abstract Background Amyloid plaques and neurofibrillary tangles, the molecular lesions that characterize Alzheimer’s disease (AD) other forms of dementia, are emerging as determinants proteinopathies ‘beyond brain’. This study aims to establish tau’s putative pathophysiological mechanistic roles potential future therapeutic targeting tau in heart failure (HF). Methods results A mouse model tauopathy human myocardial brain tissue from patients with HF, AD, controls was employed this study....
Extracellular adenosine salvage and AMPK activation are enhanced in a stage-specific manner during human B cell development.
Recent advances in proteomic technologies have made high-throughput profiling of low-abundance proteins large epidemiological cohorts increasingly feasible. We investigated whether aptamer-based could identify biomarkers associated with future development type 2 diabetes (T2DM) beyond known risk factors. identified dozens markers highly significant associations T2DM across longitudinal (n = 2839) followed for up to 16 years. leveraged proteomic, metabolomic, genetic, and clinical data from...
Metabolic responses to exercise training are variable. Metabolite profiling may aid in the clinical assessment of an individual's responsiveness interventions.To investigate association between a novel circulating biomarker hepatic fat, dimethylguanidino valeric acid (DMGV), and metabolic health traits before after 20 weeks endurance training.This study involved cross-sectional longitudinal analyses Health, Risk Factors, Exercise Training, Genetics (HERITAGE) Family Study, 20-week,...
ABSTRACT Purpose High-throughput profiling of metabolic status (metabolomics) allows for the assessment small-molecule metabolites that may participate in exercise-induced biochemical pathways and corresponding cardiometabolic risk modification. We sought to describe changes a diverse set plasma metabolite profiles patients undergoing chronic exercise training assess relationship between response exercise. Methods A secondary analysis was performed 216 middle-age abdominally obese men women...
Mitral valve prolapse (MVP) is a commonly occurring heart condition defined by enlargement and superior displacement of the mitral leaflet(s) during systole. Although seen as standalone disorder, MVP has also been described in case reports small studies patients with various genetic syndromes. In this review, we analyzed prevalence within syndromes where an association to previously reported. We further discussed shared biological pathways that cause these syndromes, well how turn causes...
Intercellular interactions among cardiac cell populations are essential for morphogenesis, yet the molecular mechanisms orchestrating these events remain incompletely understood. Dachsous1 (Dchs1), an atypical cadherin linked to mitral valve prolapse, is a core planar polarity protein whose function in developing heart has not been fully elucidated. To address this, we generated Dchs1-HA knock-in mouse model define its spatial, temporal, and cellular expression patterns. Using...
<h3>Importance</h3> Clinical practice guidelines currently endorse a reliance on clinical symptoms of overt left ventricular (LV) failure to time aortic valve replacement for severe stenosis; however, delayed can result in irreversible LV injury and adverse outcomes. Blood metabolomic signatures possess prognostic value heart failure; this study assesses whether they are informative stenosis. <h3>Objective</h3> To evaluate the reflecting extent maladaptive remodeling patients with end-stage...
Recent studies have linked mitral valve prolapse to localized myocardial fibrosis, ventricular arrhythmia, and even sudden cardiac death independent of regurgitation or hemodynamic dysfunction. The primary mechanistic theory is rooted in increased papillary muscle traction forces due prolapse, yet no biomechanical evidence exists showing forces. Our objective was evaluate the relationship between forces, leveraging advances ex vivo modeling technologies. We hypothesized that with limited...
<title>Abstract</title> Hypermobile Ehlers-Danlos syndrome (hEDS) is a common heritable connective tissue disorder that lacks known genetic etiology. To identify contributions to hEDS, whole exome sequencing was performed on families and cohort of sporadic hEDS patients. A missense variant in <italic>Kallikrein-15</italic> (KLK15 p. Gly226Asp<italic>)</italic>,<italic> </italic>segregated with disease two burden analyses 197 patients revealed enrichment variants within the...
Novel biomarkers of type 2 diabetes (T2D) and response to preventative treatment in individuals with similar clinical risk may highlight metabolic pathways that are important disease development. We profiled 331 metabolites 2,015 baseline plasma samples from the Diabetes Prevention Program (DPP). Cox models were used determine associations between incident T2D, as well whether differed by group (i.e., lifestyle [ILS], metformin [MET], or placebo [PLA]), over an average 3.2 years follow-up....
Trametinib is a MEK1 (mitogen-activated extracellular signal-related kinase 1) inhibitor used in the treatment of BRAF (rapid accelerated fibrosarcoma B-type)–mutated metastatic melanoma. Roughly 11% patients develop cardiomyopathy following long-term trametinib exposure. Although described clinically, molecular landscape cardiotoxicity has not been characterized. The aim this study was to test hypothesis that promotes widespread transcriptomic and cellular changes consistent with oxidative...
Purines are the building blocks of DNA/RNA, energy substrates, and cofactors. Purine metabolites, including ATP, GTP, NADH, coenzyme A, essential molecules in diverse biological processes such as metabolism, signal transduction, enzyme activity. When purine levels increase, excess purines either recycled to synthesize metabolites or catabolized end product uric acid. catabolism increases during states low oxygen tension (hypoxia ischemia), but this metabolic pathway is incompletely...