- Cardiomyopathy and Myosin Studies
- Pluripotent Stem Cells Research
- COVID-19 Clinical Research Studies
- Long-Term Effects of COVID-19
- Tissue Engineering and Regenerative Medicine
- Inflammasome and immune disorders
- Electrospun Nanofibers in Biomedical Applications
- Infective Endocarditis Diagnosis and Management
- Congenital heart defects research
- CRISPR and Genetic Engineering
- Coronary Artery Anomalies
- Metabolism, Diabetes, and Cancer
- Cardiac Valve Diseases and Treatments
- Systemic Sclerosis and Related Diseases
- Plant Stress Responses and Tolerance
- Bioinformatics and Genomic Networks
- Cardiac Imaging and Diagnostics
- Muscle Physiology and Disorders
- Plant Gene Expression Analysis
- Plant Micronutrient Interactions and Effects
- Congenital Heart Disease Studies
- Cellular Mechanics and Interactions
- Viral Infections and Immunology Research
- Chemotherapy-induced cardiotoxicity and mitigation
- Aortic aneurysm repair treatments
Cleveland Clinic
2020-2024
Vanderbilt University Medical Center
2014-2023
Harvard University
2015-2018
Vanderbilt University
2012-2016
Vanderbilt-Ingram Cancer Center
2016
Brigham and Women's Hospital
2015
Calvin University
2014-2015
Duke University
2011-2012
Human mutations that truncate the massive sarcomere protein titin [TTN-truncating variants (TTNtvs)] are most common genetic cause for dilated cardiomyopathy (DCM), a major of heart failure and premature death. Here we show cardiac microtissues engineered from human induced pluripotent stem (iPS) cells powerful system evaluating pathogenicity gene variants. We found certain missense mutations, like TTNtvs, diminish contractile performance pathogenic. By combining functional analyses with RNA...
In patients with COVID-19, granulocyte-macrophage colony stimulating factor (GM-CSF) might be a mediator of the hyperactive inflammatory response associated respiratory failure and death. We aimed to evaluate whether mavrilimumab, monoclonal antibody GM-CSF receptor, would improve outcomes in COVID-19 pneumonia systemic hyperinflammation.This investigator-initiated, multicentre, double-blind, randomised trial was done at seven hospitals USA. Inclusion required hospitalisation, pneumonia,...
AMP-activated protein kinase (AMPK) is a metabolic enzyme that can be activated by nutrient stress or genetic mutations. Missense mutations in the regulatory subunit, PRKAG2, activate AMPK and cause left ventricular hypertrophy, glycogen accumulation, pre-excitation. Using human iPS cell models combined with three-dimensional cardiac microtissues, we show activating PRKAG2 increase microtissue twitch force enhancing myocyte survival. Integrating RNA sequencing metabolomics, remodeled global...
In patients with Covid-19, myocardial injury and increased inflammation are associated morbidity mortality. We designed a proof-of-concept randomized controlled trial to evaluate whether treatment canakinumab prevents progressive respiratory failure worsening cardiac dysfunction in SARS-CoV2 infection, injury, high levels of inflammation.The primary hypothesis is that canakiumab will shorten time recovery.The three C study (canakinumab Covid-19 Cardiac Injury, NCT04365153) double-blind,...
Botanists have long been interested in the reasons for genetic variation among individuals, populations, and species of plants. The anthocyanin pathway is ideal studying evolution such phenotypic variation.
Cardiotoxicity is a well-established complication of oncology therapies. Cardiomyopathy resulting from anthracyclines classic example. In the past decade, an explosion novel cancer therapies, often targeted and more specific than conventional has revolutionized therapy dramatically changed prognosis. However, some these therapies have introduced assortment cardiovascular (CV) complications. At times, devastating outcomes only become apparent after drug approval limited use potent There...
During cardiomyocyte maturation, the centrosome, which functions as a microtubule organizing center in cardiomyocytes, undergoes dramatic structural reorganization where its components reorganize from being localized at centriole to nuclear envelope. This developmentally programmed process, referred centrosome reduction, has been previously associated with cell cycle exit. However, understanding of how this process influences biology, and whether disruption results human cardiac disease,...
Natural variation in the regulation of accumulation mineral nutrients and trace elements plant tissues is crucial to metabolism, development, survival across different habitats. Studies genetic basis natural nutrient metabolism have been facilitated by development ionomics. Ionomics a functional genomic approach for identification genes gene networks that regulate elemental composition, or ionome, an organism. In this study, we evaluated divergence composition between inland annual coastal...
Single coronary artery (SCA) is a rare congenital anomaly where blood to the heart supplied through common trunk. Identifying these abnormalities important because some variants can compromise myocardial flow and increase risk of sudden cardiac death.
Transcatheter aortic valve replacement (TAVR) has emerged as a viable treatment option for patients with symptomatic stenosis across all surgical risk groups. Although the need alternative access to transfemoral is becoming less frequent due better device profiles, there continued such options. Common approaches used today include subclavian, carotid, caval, aortic, or apical. However, transseptal approach not been described current S3 delivery system. We present, our knowledge, first...
BACKGROUND Dobutamine stress echocardiography (DSE) is commonly used for cardiovascular assessment before orthotopic liver transplantation (OLT). The coronary artery calcium score (CACS) a useful screening tool disease (CAD). We aimed to compare the sensitivity and specificity of DSE CACS CAD in OLT candidates. MATERIAL AND METHODS A total 265 1589 patients who underwent at our center between 2008 2019 had preoperative angiography (CAG). Of these, 173 133 CT scan suitable calculation within...
Introduction: Dilated cardiomyopathy (DCM) is one of the most common cardiovascular disorders with a prevalence 1:250 patients. Patients DCM develop left ventricular dilation, systolic dysfunction, and ultimately heart failure. While can occur due to acquired conditions, our group recently identified mutations in giant sarcomere protein titin (TTN) as genetic cause DCM, occurring 15-20% familial or sporadic cases. Truncation A-band TTN are enriched cases, while truncation I-band less...
Introduction: Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease affecting 1 in 500 people and leading cause of sudden cardiac death young adults. Mutations β-myosin heavy chain ( MYH7 ) account for one-third cases, but underlying pathogenesis remains unclear. In this study, we investigated myocytes derived from CRISPR-Cas9-engineered isogenic induced pluripotent stem cell cardiomyocytes (iPSC-CMs) with a missense mutation Val606Met by single-cell microtissue...
Congenital dilated cardiomyopathy (cDCM) is a rare but often fatal disease. In most cases, there no family history, and its etiology unknown. A major hurdle to elucidating mechanistic understanding of congenital cardiomyopathy, primary cardiomyopathies in general, has been lack access diseased human cardiac tissues. Recent advances patient-derived induced pluripotent stem cells (iPSCs) now enable production cardiomyocytes (iPSC-CMs) allows for systematic study normal cardiomyocytes. We...
There is a tremendous interest in human cardiomyocytes generated from patient-derived induced pluripotent stem cells (iPSC-CMs) for the study and possible treatment of heart diseases. Despite their vast potential, significant impediment to broader application iPSC-CMs myocyte biology structural functional immaturity iPSC-CMs. Growing evidence indicates that synthetic polymers utilized as extracellular substrates can exert effects on vitro tissue generation, although underlying mechanisms...