A5064955311- Genetic Associations and Epidemiology
- Acute Myeloid Leukemia Research
- Cardiovascular Health and Risk Factors
- Lipoproteins and Cardiovascular Health
- Mobile Health and mHealth Applications
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Cardiac Health and Mental Health
- Cancer Genomics and Diagnostics
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Telemedicine and Telehealth Implementation
- Aortic aneurysm repair treatments
- Cancer, Lipids, and Metabolism
- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- Aortic Disease and Treatment Approaches
- Lipid metabolism and disorders
- Kruppel-like factors research
- Cardiac Imaging and Diagnostics
- Peroxisome Proliferator-Activated Receptors
- Health Systems, Economic Evaluations, Quality of Life
- Acute Myocardial Infarction Research
- Immune Cell Function and Interaction
- Viral-associated cancers and disorders
- Heart Failure Treatment and Management
- Congenital heart defects research
Broad Institute
2020-2025
Massachusetts General Hospital
2018-2025
Harvard University
2016-2025
Massachusetts Institute of Technology
2023
AstraZeneca (United Kingdom)
2022
Brigham and Women's Hospital
2020
Beth Israel Deaconess Medical Center
2016
Case Western Reserve University
2010-2011
Current paradigms suggest that two macrophage subsets, termed M1 and M2, are involved in inflammation host defense. While the distinct functions of M2 macrophages have been intensively studied — former considered proinflammatory latter antiinflammatory determinants their speciation incompletely understood. Here we report our studies identify Krüppel-like factor 4 (KLF4) as a critical regulator polarization. Macrophage KLF4 expression was robustly induced strongly reduced macrophages,...
Abstract The current understanding of the genetic determinants thoracic aortic aneurysms and dissections (TAAD) has largely been informed through studies rare, Mendelian forms disease. Here, we conducted a genome-wide association study (GWAS) TAAD, testing ~25 million DNA sequence variants in 8,626 participants with 453,043 without TAAD Million Veteran Program, replication an independent sample 4,459 individuals 512,463 from six cohorts. We identified 21 risk loci, 17 which have not...
Guidelines for primary prevention of atherosclerotic cardiovascular disease (ASCVD) recommend a risk calculator (ASCVD score) to estimate 10-year major adverse events (MACE). Because the necessary inputs are often missing, complementary approaches opportunistic assessment desirable.
The mechanisms by which exercise mediates its multiple cardiac benefits are only partly understood. Prior comprehensive analyses of the transcriptional components and microRNAs dynamically regulated suggest that CBP/p300-interacting protein CITED4 is a downstream effector in both networks. While has documented functional consequences neonatal cardiomyocytes vitro, nothing known about effects adult heart. To investigate impact expression animals, we generated transgenic mice with regulated,...
<h3>Importance</h3> Spontaneous coronary artery dissection (SCAD) is an increasingly recognized nonatherosclerotic cause of acute myocardial infarction enriched among individuals with early-onset but unclear etiology. <h3>Objective</h3> To assess which genes contribute to the development SCAD. <h3>Design, Setting, and Participants</h3> prioritize influencing risk for SCAD, whole-exome sequencing was performed SCAD in discovery replication cohorts from a tertiary care hospital outpatient...
Dyslipoproteinemia often involves simultaneous derangements of multiple lipid traits. We aimed to evaluate the phenotypic and genetic characteristics combined disturbances in a general population-based cohort.
Abstract Coronary artery disease (CAD) is the leading cause of death among adults worldwide. Accurate risk stratification can support optimal lifetime prevention. Current methods lack ability to incorporate new information throughout life course or combine innate genetic factors with acquired risk. We designed a general multistate model (MSGene) estimate age-specific transitions across 10 cardiometabolic states, dependent on clinical covariates and CAD polygenic score. This handle...
BACKGROUND: Earlier identification of high coronary artery disease (CAD) risk individuals may enable more effective prevention strategies. However, existing 10-year frameworks are ineffective at earlier identification. We sought to understand how the variable importance genomic and clinical factors across life stages significantly improve lifelong CAD event prediction. METHODS: A longitudinal study was performed using data from 2 cohort studies: FOS (Framingham Offspring Study) with 3588...
Mass General Brigham, an integrated healthcare system based in the Greater Boston area of Massachusetts, annually serves 1.5 million patients. We established Brigham Biobank (MGBB), encompassing 142,238 participants, to unravel intricate relationships among genomic profiles, environmental context, and disease manifestations within clinical practice. In this study, we highlight impact ancestral diversity MGBB by employing population genetics, geospatial assessment, association analyses rare...
BackgroundThe interval between inpatient hospitalization for symptomatic coronary artery disease (CAD) and post-discharge office consultation is a vulnerable period adverse events.MethodsContent was customized on smartphone app-based platform hospitalized patients receiving percutaneous intervention (PCI) which included education, tracking, reminders live health coaches. We conducted single-arm open-label pilot study of the app at two academic medical centers in single system, with subjects...
Structured Abstract Importance Earlier identification of high coronary artery disease (CAD) risk individuals may enable more effective prevention strategies. However, existing 10-year frameworks are ineffective at earlier identification. Understanding the variable importance genomic and clinical factors across life stages significantly improve lifelong CAD event prediction. Objective To assess time-varying significance in estimation various age groups. Design, Setting, Participants A...
Abstract With age, acquired mutations can cause clonal expansion of hematopoietic stem cells (HSC). This hematopoiesis indeterminate potential (CHIP) leads to an increased predisposition numerous diseases including blood cancer and cardiovascular disease. Here, we report multi- ancestry genome-wide association meta-analyses CHIP among 323,112 individuals (19.5% non-European; 5.3% have CHIP). We identify 15 significant regions nominate additional loci through multi-trait analyses, highlight...
Age is the dominant risk factor for infectious diseases, but mechanisms linking two are incompletely understood1,2. Age-related mosaic chromosomal alterations (mCAs) detected from blood-derived DNA genotyping, structural somatic variants associated with aberrant leukocyte cell counts, hematological malignancy, and mortality3-11. Whether mCAs represent independent factors infection unknown. Here we use genome-wide genotyping of blood to show that predispose diverse diseases. We analyzed...
We aimed to discover loci associated with triglyceride (TG) levels in the context of type 2 diabetes (T2D). conducted a genome-wide association study (GWAS) 424,120 genotyped participants UK Biobank (UKB) T2D status and TG levels.
Abstract Background Somatic mutations in blood indicative of clonal hematopoiesis indeterminate potential (CHIP), particularly DNMT3A , TET2 and JAK2 are associated with an increased risk hematologic malignancy, coronary artery disease, all-cause mortality. However, whether CHIP is peripheral disease (PAD) remains unknown. In addition, chemotherapy frequently causes DNA Damage Repair (DDR) genes TP53 PPM1D caused by somatic DDR results atherosclerosis unclear. We sought to test CHIP, genes,...
Key Findings•The current landscape of digital health usage during the coronavirus disease 2019 (COVID-19) pandemic highlights its potential for widespread use in cardiovascular prevention.•Harnessing full benefit primary prevention will require timely and thoughtful research investment.•Research should be aimed at demonstrating benefits improving patient access to care, quality life, usability providers, care outcomes; streamlining workflow; limiting costs.•Special must taken ensure...