A5047212488- Congenital heart defects research
- Congenital Heart Disease Studies
- Cardiac tumors and thrombi
- Cardiomyopathy and Myosin Studies
- Aortic Disease and Treatment Approaches
- Cardiac Valve Diseases and Treatments
- Cardiac Structural Anomalies and Repair
- Coronary Artery Anomalies
- Sarcoma Diagnosis and Treatment
- Lipoproteins and Cardiovascular Health
- Cardiac electrophysiology and arrhythmias
- Cardiovascular Effects of Exercise
- Vascular Tumors and Angiosarcomas
- Connective tissue disorders research
- Cardiac Arrhythmias and Treatments
- Atherosclerosis and Cardiovascular Diseases
- Cancer Cells and Metastasis
- Cardiovascular Function and Risk Factors
- Peptidase Inhibition and Analysis
- Cell Adhesion Molecules Research
- Aortic aneurysm repair treatments
- Tracheal and airway disorders
- Tissue Engineering and Regenerative Medicine
- RNA modifications and cancer
- Sports injuries and prevention
Boston Biomedical Research Institute
2016-2022
Novartis (United States)
2016-2022
Cornell University
2006-2021
Novartis (Switzerland)
2021
Novartis Institutes for BioMedical Research
2021
American College of Cardiology
2018
BG University Hospital Bergmannsheil Bochum
2018
Palo Alto Institute
2018
Harvard University
1992-2014
Philadelphia College of Osteopathic Medicine
2014
Mutations in the gene encoding homeobox transcription factor NKX2-5 were found to cause nonsyndromic, human congenital heart disease. A dominant disease locus associated with cardiac malformations and atrioventricular conduction abnormalities was mapped chromosome 5q35, where , a Drosophila tinman homolog, is located. Three different mutations identified. Two are predicted impair binding of target DNA, resulting haploinsufficiency, third potentially augments target-DNA binding. These data...
The Holt-Oram syndrome is an autosomal dominant condition characterized by skeletal abnormalities that are frequently accompanied congenital cardiac defects. cause of these disparate clinical features unknown. To identify the chromosomal location gene, we performed and genetic studies.
<h3>Importance</h3> Clonal hematopoiesis of indeterminate potential (CHIP) is associated with increased risk atherosclerotic cardiovascular disease, and mouse experiments suggest that CHIP related to<i>Tet2</i>loss function in myeloid cells accelerates atherosclerosis via augmented interleukin (IL) 1β signaling. <h3>Objective</h3> To assess whether individuals have greater event reduction response to IL-1β neutralization the Canankinumab Anti-inflammatory Thrombosis Outcomes Trial (CANTOS)....
To better understand the role of TBX5, a T-box containing transcription factor in forelimb and heart development, we have studied clinical features Holt–Oram syndrome caused by 10 different TBX5 mutations. Defects predicted to create null alleles substantial abnormalities both limb heart. In contrast, missense mutations produced distinct phenotypes: Gly80Arg significant cardiac malformations but only minor skeletal abnormalities; Arg237Gln Arg237Trp extensive upper less abnormalities. Amino...
Cardiac myxomas are benign mesenchymal tumors that can present as components of the human autosomal dominant disorder Carney complex. Syndromic cardiac associated with spotty pigmentation skin and endocrinopathy. Our linkage analysis mapped a complex gene defect to chromosome 17q24. We now demonstrate PRKAR1α encoding R1α regulatory subunit cAMP-dependent protein kinase A (PKA) maps this 17q24 locus. Furthermore, we show frameshift mutations in three unrelated families result...
Background —Aneurysms and dissections affecting the ascending aorta are associated primarily with degeneration of aortic media, called medial necrosis. Families identified dominant inheritance thoracic aneurysms (TAA/dissections) indicate that single gene mutations can cause necrosis in absence an syndrome. Methods Results —Fifteen families were multiple members TAAs/dissections. DNA from affected 2 was used for a genome-wide search location defective by use random polymorphic markers. The...
We have mapped a disease locus for Wolff-Parkinson-White syndrome (WPW) and familial hypertrophic cardiomyopathy (FHC) segregating in large kindred to chromosome 7 band q3. Although WPW FHC been observed members of the same family prior studies, relationship between these two diseases has remained enigmatic. A with 25 surviving individuals who are affected by one or both conditions was studied. The is closely linked loci D7S688, D7S505, D7S483 (maximum point LOD score at D7S505 7.80 theta =...
Background —Intracardiac myxomas are significant causes of cardiovascular morbidity and mortality through embolic stroke heart failure. In the autosomal dominant syndrome Carney complex, intracardiac arise in setting lentiginosis other lesions associated with cutaneous hyperpigmentation, extracardiac myxomas, nonmyxomatous tumors. Genetic factors that regulate cardiac tumor growth remain unknown. Methods Results —We used molecular genetic techniques linkage analysis to study 4 kindreds...
We report that Id knockout mouse embryos display multiple cardiac defects, but mid-gestation lethality is rescued by the injection of 15 wild-type embryonic stem (ES) cells into mutant blastocysts. Myocardial markers altered in are restored to normal throughout chimeric myocardium. Intraperitoneal ES female mice before conception also partially rescues phenotype with no incorporation cells. Insulin-like growth factor 1, a long-range secreted factor, combination WNT5a, locally likely account...
Atherosclerotic cardiovascular disease (CVD) is a major health problem in the United States and around world. Evidence accumulated over decades convincingly demonstrates that family history parent or sibling associated with atherosclerotic CVD, manifested as coronary heart disease, stroke, and/or peripheral arterial disease. Although there are several mendelian disorders contribute to most common forms of CVD believed be multifactorial result from many genes, each relatively small effect...
Abstract Context The CD40-CD154 co-stimulatory pathway plays an important role in the pathogenesis of Graves disease (GD) by promoting autoreactive B-cell activation. Objective Evaluate efficacy and safety a human, blocking, nondepleting anti-CD40 monoclonal antibody, iscalimab, hyperthyroid patients with GD. Design Open-label, phase II proof-of-concept study. Setting Multicenter. Patients Fifteen Intervention received 5 doses iscalimab at 10 mg/kg intravenously over 12 weeks. Main outcome...
Background —Aortic aneurysms cause significant mortality, and >20% relate to hereditary disorders. Familial aortic aneurysm (FAA) has been described in such conditions as the Marfan Ehlers-Danlos type IV syndromes, due defects fibrillin-1 III procollagen genes, respectively. Other gene that isolated aneurysms, however, have not thus far described. Methods Results —We studied 3 families affected by FAA. No family met diagnostic criteria for either or syndrome. Echocardiography defined...
Carney complex (CNC) is a familial multiple neoplasia syndrome characterized by cardiac and extracardiac myxomas in the setting of spotty skin pigmentation endocrinopathy. We previously identified PRKAR1A (regulatory subunit 1α protein kinase A) mutations CNC. Mutational analyses gene 51 unrelated CNC probands now detect 65%. All mutations, except for one unique missense mutation, lead to haploinsufficiency. Therefore, we studied consequences prkar1a haploinsufficiency mice. Although did not...