A5068991885- Metabolomics and Mass Spectrometry Studies
- Genetic Associations and Epidemiology
- MicroRNA in disease regulation
- Epigenetics and DNA Methylation
- Advanced Proteomics Techniques and Applications
- Cancer-related molecular mechanisms research
- Mass Spectrometry Techniques and Applications
- Hormonal Regulation and Hypertension
- Bioinformatics and Genomic Networks
- Circular RNAs in diseases
- Chronic Obstructive Pulmonary Disease (COPD) Research
- GDF15 and Related Biomarkers
- Genetic Mapping and Diversity in Plants and Animals
- Genetic Syndromes and Imprinting
- Receptor Mechanisms and Signaling
- Nutrition, Genetics, and Disease
- Cardiovascular Disease and Adiposity
- Atherosclerosis and Cardiovascular Diseases
- Cardiovascular Health and Risk Factors
- Health, Environment, Cognitive Aging
- Connective tissue disorders research
- Adipokines, Inflammation, and Metabolic Diseases
- Renin-Angiotensin System Studies
- Clusterin in disease pathology
- RNA modifications and cancer
National Heart Lung and Blood Institute
2015-2024
National Institutes of Health
2014-2024
Framingham Heart Study
2015-2024
Naval Research Laboratory Information Technology Division
2019-2024
Boston University
2014-2022
Massachusetts General Hospital
2013-2021
Center for Information Technology
2013-2014
BG Medicine (United States)
2009-2014
Rutgers, The State University of New Jersey
2014
Harvard University
2013-2014
Identifying genetic variants associated with circulating protein concentrations (protein quantitative trait loci; pQTLs) and integrating them from genome-wide association studies (GWAS) may illuminate the proteome's causal role in disease bridge a knowledge gap regarding SNP-disease associations. We provide results of GWAS 71 high-value cardiovascular proteins 6861 Framingham Heart Study participants independent external replication. report mapping over 16,000 pQTL their functional...
The link between DNA methylation, obesity, and adiposity-related diseases in the general population remains uncertain.We conducted an association study of body mass index (BMI) differential methylation for over 400,000 CpGs assayed by microarray whole-blood-derived from 3,743 participants Framingham Heart Study Lothian Birth Cohorts, with independent replication three external cohorts 4,055 participants. We examined variations whole blood gene expression Mendelian randomization analyses to...
The discovery of novel and highly predictive biomarkers cardiovascular disease (CVD) has the potential to improve risk-stratification methods may be informative regarding biological pathways contributing disease.
The proteome of normal male urine from a commercial pooled source has been examined using direct liquid chromatography-tandem mass spectrometry (LC-MS/MS). entire urinary protein mixture was denatured, reduced and enzymatically digested prior to LC-MS/MS analysis hybrid-quadrupole time-of-flight spectrometer (Q-TOF) perform data-dependent ion selection fragmentation. To fragment as many peptides possible, the analyzed four separate times, with selecting ions for fragmentation subset range...
Five novel peptides were identified in the brains of mice lacking active carboxypeptidase E, a neuropeptide-processing enzyme. These are produced from single precursor, termed proSAAS, which is present human, mouse, and rat. ProSAAS mRNA expressed primarily brain other neuroendocrine tissues (pituitary, adrenal, pancreas); within brain, broadly distributed among neurons. When AtT-20 cells, proSAAS secreted via regulated pathway also processed at paired-basic cleavage sites into smaller...
Abstract Owing to the complexity of higher eukaryotic cells, characterization a complete proteome is likely be difficult achieve. However, advantage can taken cell compartmentalization build organelle proteomes, which moreover viewed as specialized tools study specifically biology and “physiology” target organelle. Within this frame, we report here construction human mitochondrial proteome, using placenta source tissue. Protein identification was carried out mainly by peptide mass...
Objective— Genetic approaches have identified numerous loci associated with coronary heart disease (CHD). The molecular mechanisms underlying CHD gene–disease associations, however, remain unclear. We hypothesized that genetic variants both strong and subtle effects drive gene subnetworks in turn affect CHD. Approach Results— surveyed CHD-associated interactions by constructing coexpression networks using whole blood expression profiles from 188 cases age- sex-matched controls. Twenty-four...
Identification of microRNA expression quantitative trait loci (miR-eQTL) can yield insights into regulatory mechanisms transcription, and help elucidate the role as mediators complex traits. Here we present a miR-eQTL mapping study whole blood from 5,239 individuals, identify 5,269 cis-miR-eQTLs for 76 mature microRNAs. Forty-nine per cent are located 300–500 kb upstream their associated intergenic microRNAs, suggesting that distal elements may affect interindividual variability in levels....
Objective— To identify transcriptomic biomarkers of coronary heart disease (CHD) in 188 cases with CHD and age- sex-matched controls who were participants the Framingham Heart Study. Approach Results— A total 35 genes differentially expressed versus at false discovery rate<0.5, including GZMB , TMEM56 GUK1 . Cluster analysis revealed 3 gene clusters associated CHD, 2 linked to increased erythrocyte production a third reduced natural killer T cell activity CHD. Exon-level results...
Genome-wide association studies (GWAS) have identified numerous loci associated with blood pressure (BP). The molecular mechanisms underlying BP regulation, however, remain unclear. We investigated BP-associated by integrating GWAS whole mRNA expression profiles in 3,679 individuals, using network approaches. transcriptomic signatures at the single-gene and coexpression module levels were identified. Four modules as potentially causal based on genetic inference because expression-related...
Objective— Incorporation of novel plasma protein biomarkers may improve current models for prediction atherosclerotic cardiovascular disease (ASCVD) risk. Approach and Results— We used discovery mass spectrometry (MS) to determine concentrations 861 proteins in 135 myocardial infarction (MI) cases matched controls. Then, we measured 59 markers by targeted MS 336 ASCVD case–control pairs. Associations with MI or were tested single-marker multiple-marker analyses adjusted established risk...
BackgroundMetabolic syndrome (MetS), the clustering of metabolic risk factors, is associated with cardiovascular disease risk. We sought to determine if dysregulation lipidome may contribute factors.MethodsWe measured 154 circulating lipid species in 658 participants from Framingham Heart Study (FHS) using liquid chromatography-tandem mass spectrometry and tested for associations obesity, dysglycemia, dyslipidemia. Independent external validation was three independent cohorts. Follow-up data...
CXCL12 encodes stromal cell-derived factor 1α (SDF-1), which binds to the receptor encoded by CXCR4. Variation at locus is associated with coronary artery disease and endothelial progenitor cell numbers, whereas variation CXCR4 leukocyte telomere length, has been shown be disease. Therefore, we examined relationships of plasma SDF-1 levels cardiovascular (CVD)-related outcomes, risk factors, cells.SDF-1 was measured in 3359 Framingham Heart Study participants. We used Cox regression examine...
Background— Cardiovascular disease (CVD) reflects a highly coordinated complex of traits. Although genome-wide association studies have reported numerous single nucleotide polymorphisms (SNPs) to be associated with CVD, the role most these variants in processes remains unknown. Methods and Results— We built CVD network using 1512 SNPs 21 traits (at P ≤5×10 −8 ) cross-linked different by virtue their shared SNP associations. then explored whole blood gene expression relation 5257 participants...
Cigarette smoking increases risk for multiple diseases. MicroRNAs regulate gene expression and may play a role in smoking-induced target organ damage. We sought to describe microRNA signature of cigarette relate it smoking-associated clinical phenotypes, expression, lung inflammatory signaling.
The roles of microRNAs (miRNAs) in coronary heart disease (CHD) have not been well characterized. This study sought to systematically characterize the complex genomic architecture CHD by integrating whole blood miRNA and mRNA expression with genetic variation 186 cases controls.At false discovery rate <0.2, 15 miRNAs were differentially expressed between controls. To explore regulatory mechanisms, we integrated genome-wide genotype data investigate associations relationships miRNAs. We...
Background GDF15 (growth differentiation factor 15) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) may offer promise as biomarkers for cognitive outcomes, including dementia. We determined the association of these with outcomes in a community-based cohort. Methods Results Plasma (n=1603) levels (n=1590) (53% women; mean age, 68.7 years) were measured dementia-free Framingham Offspring cohort participants at examination 7 (1998-2001). Participants followed up incident Secondary...
Drug-induced liver injury (DILI) is the primary adverse event that results in withdrawal of drugs from market and a frequent reason for failure drug candidates development. The Liver Toxicity Biomarker Study (LTBS) an innovative approach to investigate DILI because it compares molecular events produced vivo by compound pairs (a) are similar structure mechanism action, (b) associated with few or no signs toxicity preclinical studies, (c) show marked differences hepatotoxic potential. LTBS...
Abstract Objective To determine the association between plasma insulin‐like growth factor binding protein 2 (IGFBP‐2) and cognitive outcomes. Methods We measured IGFBP‐2 levels in 1596 (53% women, mean age 68.7 [SD 5.7] years) dementia‐free Framingham Offspring cohort participants 1998 2001. Multivariable Cox proportional hazards models related to subsequent risk of incident dementia Alzheimer’s disease. MRI brain measures performance were included as secondary Results During a median...
Genetic variation in the clusterin gene has been associated with Alzheimer Disease (AD), and protein is thought to play a mechanistic role. We explored associations of plasma levels incident dementia, AD, stroke.Plasma was assessed 1532 nondemented participants from Framingham Study Offspring cohort between 1998 2001 (mean age, 69 ± 6; 53% women). related risk stroke using Cox-proportional hazards models examined potential interactions.A significant interaction age observed. Clusterin...
Background Fibroblast growth factor 23 is an emerging vascular biomarker, recently associated with cerebral small vessel disease and poor cognition in patients on dialysis. It also interacts klotho, anti-aging enhancing protein. Objective To determine if circulating (FGF23) new-onset cognitive outcomes a community-based cohort of cognitively healthy adults long-term follow-up. Methods We measured serum FGF23 levels 1537 [53% women, mean age 68.7 (SD 5.7)] dementia-free Framingham Offspring...
Background Obesity may be associated with a range of cardiometabolic manifestations. We hypothesized that proteomic profiling provide insights into the biological pathways contribute to various obesity‐associated traits. sought identify signatures obesity and examine overlap related traits, including abdominal adiposity, insulin resistance, adipose depots. Methods Results measured 71 circulating cardiovascular disease protein biomarkers in 6981 participants (54% women; mean age, 49 years)....