A5028310635- Cardiomyopathy and Myosin Studies
- RNA modifications and cancer
- Adipokines, Inflammation, and Metabolic Diseases
- Cardiac Structural Anomalies and Repair
- RNA Research and Splicing
- Atherosclerosis and Cardiovascular Diseases
- Peroxisome Proliferator-Activated Receptors
- Extracellular vesicles in disease
- Cardiac Valve Diseases and Treatments
- Genomics and Rare Diseases
- Lipoproteins and Cardiovascular Health
- Chemotherapy-induced cardiotoxicity and mitigation
- Congenital heart defects research
- Wound Healing and Treatments
- Atrial Fibrillation Management and Outcomes
- Eicosanoids and Hypertension Pharmacology
- S100 Proteins and Annexins
- Synthesis and Biological Evaluation
- Cardiovascular Effects of Exercise
- Circular RNAs in diseases
- Cardiovascular Health and Risk Factors
- Retinopathy of Prematurity Studies
- Retinal and Macular Surgery
- Cancer, Stress, Anesthesia, and Immune Response
- Cell death mechanisms and regulation
Northwell Health
2024
Harvard University
2017-2023
Massachusetts General Hospital
2023
Brigham and Women's Hospital
2012-2021
UC San Diego Health System
2021
University of Kentucky
2020
Patel Hospital
2012-2019
Augusta University
2019
Florida State University
2015-2017
New York University
2015-2017
Background: Cancer therapy–induced cardiomyopathy (CCM) is associated with cumulative drug exposures and preexisting cardiovascular disorders. These parameters incompletely account for substantial interindividual susceptibility to CCM. We hypothesized that rare variants in genes contribute Methods: studied 213 patients CCM from 3 cohorts: retrospectively recruited adults diverse cancers (n=99), prospectively phenotyped breast cancer (n=73), children acute myeloid leukemia (n=41)....
Significance Sequence variants that create or eliminate splice sites are often clinically classified as of unknown significance (VUS) due to imperfect understanding RNA signals and cumbersome functional assays. In autosomal dominant disorders caused by haploinsufficiency, alter normal splicing one allele pathogenic. We developed enhanced computational tools prioritize potential splice-altering VUS used a minigene assay functionally confirm sequence variants. studying all reported across LMNA...
Background: Genome-wide association studies have identified single-nucleotide polymorphisms that are associated with an increased risk of stroke. We sought to determine whether a genetic score (GRS) could identify subjects at higher for ischemic stroke after accounting traditional clinical factors in 5 trials across the spectrum cardiometabolic disease. Methods: Subjects who had consented testing and were European ancestry from ENGAGE AF-TIMI 48 (Effective Anticoagulation Factor Xa Next...
Rationale: Death from infection is a highly heritable trait, yet there are few genetic variants with known mechanism influencing survival during septic shock.Objectives: We hypothesized that synonymous coding variant in the IL-1 receptor antagonist gene (IL1RN), rs315952, previously associated reduced risk for acute respiratory distress syndrome, would be functional and associate improved shock.Methods: used human endotoxin (LPS) model of evoked inflammatory stress to measure plasma (IL1RA)...
This document provides the full statistical analysis plan (SAP) for TRanscatheter VErsus Surgical Aortic Valve ReplacemenT in Medicare Beneficiaries with Bicuspid Stenosis (TREAT-BICUSPID) study. TREAT-BICUSPID is a retrospective, population-based cohort study of beneficiaries bicuspid aortic stenosis (AS) undergoing valve replacement (AVR) from 2012 to 2022. The was designed evaluate trends relative use transcatheter (TAVR) and surgical (SAVR) this population over time, compare 1-year...
Hereditary Nonpolyposis Colorectal Cancer (HNPCC), also known as Lynch Syndrome, is an autosomal dominant, tumor predisposing disorder usuallycaused by germline mutations in mismatch repair (MMR) genes. A subset of HNPCC, Muir-Torre Syndrome (MTS) involves MMR gene defects and generally accepted a variant HNPCC. MTS typicallycharacterized at least one visceral malignancy cutaneous neoplasm sebaceous differentiation, with or without keratoacanthomas. In either version the disorder,...
Background: Known genetic causes of congenital heart disease (CHD) explain <40% CHD cases, and interpreting the clinical significance variants with uncertain functional impact remains challenging. We aim to improve diagnostic classification in patients by assessing noncanonical splice region on RNA splicing. Methods: tested de novo from trio studies 2649 probands their parents, as well rare (allele frequency, <2×10 − 6 ) 4472 Pediatric Cardiac Genetics Consortium through a combined...
Small noncoding microRNAs (miRNAs) are important regulators of skeletal muscle size, and circulating miRNAs within extracellular vesicles (EVs) may contribute to atrophy its associated systemic effects. The purpose this study was understand how regrowth alter in vivo serum EV miRNA content. We also changes with protein synthesis, degradation, muscle, kidney, liver. subjected adult (10 mo) F344/BN rats three conditions: weight bearing (WB), hindlimb suspension (HS) for 7 days induce atrophy,...
Background: Heterozygous TTN truncating variants cause 10% to 20% of idiopathic dilated cardiomyopathy (DCM). Although which disrupt canonical splice signals (ie, invariant dinucleotide the donor site, acceptor site) at exon-intron junctions are readily recognized as variants, effects other nearby sequence variations on splicing and their contribution disease is uncertain. Methods: Rare unknown significance located in regions highly expressed exons from 203 DCM cases, 3329 normal subjects,...
Data conflict with regard to whether peroxisome proliferator-activated receptor-α agonism suppresses inflammation in humans. We hypothesized that healthy adults fenofibrate would blunt the induced immune responses endotoxin (lipopolysaccharide [LPS]), an vivo model for study of cardiometabolic inflammation.In Fenofibrate and omega-3 Fatty Acid Modulation Endotoxemia (FFAME) trial, 36 volunteers (mean age 26±7 years, mean body mass index 24±3 kg/m(2), 44% female, 72% white) were randomized...
Identification of sequence variants that create or eliminate splice sites has proven to be a significant challenge and represents one many roadblocks in the clinical interpretation rare genetic variation. Current methods identifying altering exist, however, these are limited by an imperfect understanding signals cumbersome functional assays. We have recently developed computational tool prioritizes putative splice-altering variants, moderate-throughput minigene assay confirms which alter...
Extracellular vesicles (EVs) have an important role in mediating intercellular signaling inflammation and affect the kinetics of wound healing, however, understanding mechanisms regulating these responses remains limited. Therefore, we focused on use cutaneous injury models which to study biology EVs inflammatory phase healing. For this, foreign body response using sterile subcutaneous polyvinylalcohol (PVA) sponges is ideally suited for parallel analysis immune cells without need tissue...
Takotsubo cardiomyopathy is a type of myocardial injury that marked with left ventricular contraction dysfunction. Various regions the wall may exhibit hypokinetic or hypercontractile activity. There no exact mechanism elucidated for cardiomyopathy, but it often associated triggering stressful event leads to catecholamine surge. We describe 38-year-old female who presented typical likely in setting worsening systemic lupus erythematosus (SLE) exacerbations and excessive cannabis use. The...
Background: Hypertrophic cardiomyopathy (HCM) affects at least 1 in 500 people worldwide, and results the thickening of ventricular walls reduced cardiac function. Mutations MYBPC3 , encoding myosin binding protein-C, are most common cause HCM. Previously, a highly prevalent 25bp deletion within intron 32 was described South Asian population. The d25bp variant is present approximately 100 million people, encompasses splicing branch point predicted to result abnormal exon 33. Thus, there...
Objective: To assess variation in response to endotoxemia and investigate genome-wide SNP associations with inflammatory Americans of European African ancestry. Background: Inflammation is a key component the pathophysiology cardiometabolic disease. We utilize model evoked (LPS) explore differences inflammation. hypothesized that responses would differ by race gender, be influenced genetic background. Methods: The Genetics Evoked-Responses Niacin Endotoxemia (GENE) Study recruited N=294...
Introduction: Out-of-hospital cardiac arrest (OHCA) is a leading cause of death in the US, with survival rate that less than 10% and many them surviving poor neurologic status. Therapeutic hypothermia (TH) only therapy shown to improve neurologically intact post arrest. Post syndrome complex state includes myocardial dysfunction, injury severe systemic inflammation. Previous literature suggests statins may have beneficial role other critical illnesses via several mechanisms including an...