A5082173766- Cardiac Fibrosis and Remodeling
- Signaling Pathways in Disease
- Protease and Inhibitor Mechanisms
- Estrogen and related hormone effects
- Peptidase Inhibition and Analysis
- Cardiac Ischemia and Reperfusion
- Health and Medical Research Impacts
- Cardiac Structural Anomalies and Repair
- SARS-CoV-2 and COVID-19 Research
- Nitric Oxide and Endothelin Effects
- Menopause: Health Impacts and Treatments
- Electron Spin Resonance Studies
- Mitochondrial Function and Pathology
- Biomedical and Engineering Education
- Redox biology and oxidative stress
- Proteoglycans and glycosaminoglycans research
- Cancer-related molecular mechanisms research
- vaccines and immunoinformatics approaches
- Interprofessional Education and Collaboration
- Cholesterol and Lipid Metabolism
- Sulfur Compounds in Biology
- Genetics, Bioinformatics, and Biomedical Research
- SARS-CoV-2 detection and testing
- Receptor Mechanisms and Signaling
- Global Health Workforce Issues
National Institute of Allergy and Infectious Diseases
2022-2023
Office of the Director
2023
National Institutes of Health
2007-2023
University Colleges Leuven-Limburg
2017
Federation of American Societies for Experimental Biology
2012-2015
National Heart Lung and Blood Institute
2007-2013
Center for Systems Biology
2011
Johns Hopkins University
2010
Medical University of South Carolina
2001-2008
University of Charleston
2008
Although premenopausal females have a lower risk for cardiovascular disease, the mechanism(s) are poorly understood.We tested hypothesis that cardioprotection in is mediated by altered mitochondrial protein levels and/or posttranslational modifications.Using both an vivo and isolated heart model of ischemia reperfusion (I/R), we found had less injury than males. Using proteomic methods female hearts increased phosphorylation activity aldehyde dehydrogenase (ALDH)2, enzyme detoxifies reactive...
Premenopausal females have a lower incidence of cardiovascular disease than their male counterparts, but the mechanism is unclear. Estrogen has been thought to signal through two nuclear receptors: estrogen receptor-α or receptor-β; however, third, membrane-bound receptor G protein-coupled (GPER), identified and shown bind with high affinity. To date, there little information on GPER in heart no study looked at effect activation during myocardial ischemia-reperfusion (I/R). Therefore, goal...
A potential mechanism for left ventricular (LV) remodeling after myocardial infarction (MI) is activation of the matrix metalloproteinases (MMPs). This study examined effects MMP inhibition (MMPi) on regional LV geometry and levels MI.In pigs instrumented with radiopaque markers to measure geometry, MI was created by ligating obtuse marginals circumflex artery. In first study, were randomized MMPi (n=7; PD166793, 20 mg x kg(-1) d(-1)) or only (n=7) at 5 days MI, measurements performed 2...
Induction of matrix metalloproteinases (MMPs) contributes to adverse remodeling after myocardial infarction (MI). Whether a region- and type-specific distribution MMPs occurs within the post-MI myocardium remained unknown.Ten sheep were instrumented with sonomicrometry array measure dimensions in 7 distinct regions corresponding remote, transition, MI regions. Eight served as reference controls. The relative abundance representative MMP types tissue inhibitors (TIMPs) was quantified by...
Physician scientists (researchers with either M.D. or M.D.-Ph.D. degrees) have the unique potential to combine clinical perspectives scientific insight, and their participation in biomedical research has long been an important topic for policymakers educators. Given recent changes environment, update extension of earlier studies this population was needed. Our findings show that physician are less likely take a major role than they were past. The number receiving postdoctoral training career...
Severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) emerged 20 years ago, presaging a series of subsequent infectious disease epidemics international concern. The recent emergence SARS-CoV-2 has underscored the importance targeted preparedness research to enable rapid countermeasure development during crisis. In December 2021 National Institute Allergy and Infectious Diseases (NIAID), building upon successful strategies developed response prepare for future pandemics, published...
A structural event during the evolution of a myocardial infarction (MI) is left ventricular (LV) remodeling. The mechanisms that contribute to early changes in LV remodeling post-MI period remain poorly understood. Matrix metalloproteinases (MMPs) tissue several disease states. Whether and what degree MMP activation occurs within interstitium after acute MI remains be determined. Adult pigs ( n = 15) were instrumented measure regional function interstitial levels regions served by circumflex...
The U.S. National Institutes of Health (NIH) announced last May that steps will be taken to address the over-reliance on male cells and animals in preclinical research. To further this announcement, September 2014, scientists with varying perspectives came together at Georgetown University discuss following questions. (1) What metrics should NIH use assess tangible progress policy changes designed research? (2) How effective can education reducing research what educational initiatives...
This report is based on the Federation of American Societies for Experimental Biology's symposium, "Engaging basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles," held Chevy Chase, MD, March 24–25, 2011. Meeting participants examined benefits engaging scientists translational research, challenges to their participation and roles that research institutions, funding organizations, professional societies, scientific publishers can play address these challenges.
Background— The matrix metalloproteinases (MMPs) contribute to regional remodeling after prolonged periods of ischemia and reperfusion (I/R), but specific MMP types activated during this process remain poorly understood. A novel class, the membrane-type MMPs (MT-MMPs), has been identified in myocardium, activity these not assessed vivo, particularly I/R. Methods Results— Pigs (30 kg, n=8) were instrumented with microdialysis catheters measure MT1-MMP both ischemic nonischemic (remote)...
Methionine sulfoxide reductase A (MsrA) catalytically scavenges reactive oxygen species and also repairs oxidized methionines in proteins. Increasing MsrA protects cells organs from a variety of oxidative stresses while decreasing enhances damage, but the mechanisms action have not been elucidated. single gene encodes which ∼25% is targeted to mitochondria, major site production. The other ∼75% cytosol posttranslationally modified by myristoylation. To determine relative importance each...
Past studies have clearly established that matrix metalloproteinases (MMPs) contribute to adverse myocardial remodeling with ischemia and reperfusion. However, these measured MMP levels in extracted samples, therefore whether what degree actual changes interstitial activity occur within the human myocardium context of ischemia/reperfusion remained unknown.The present study directly quantified patients (n=14) undergoing elective cardiac surgery during steady-state conditions, as well...
It is well recognized that there sex-dimorphic expression of mRNA and protein in the heart; however, underlying mechanism poorly understood. Endothelial nitric oxide synthase (eNOS) an important regulator cardiac function, levels eNOS differ between male female hearts. The aim this study was to examine whether specific microRNA (miRNA, miR) males females contributes changes eNOS. miRNA extracted from myocardium C57BL/6 mice subjected Affymetrix array. Decreased miR-222 discovered confirmed...
Myocardial remodeling is a complex process involving several molecular and cellular factors. Extracellular matrix has been implicated in the process. Historically, myocardial extracellular was thought to serve solely as means align cells provide structure tissue. Although this one of its important functions, evidence suggests that plays divergent role influencing cell behavior. This paper characterizes some notable studies on dynamic entity adverse have published over past year, which...
Background: A cause-effect relationship has been established between MMP activation and left ventricular (LV) remodeling following myocardial infarction. The goal of the present study was to examine a selective inhibitor (sMMPi) strategy that effectively spared MMP-1, -3, -7 with effect regional global in pig model Methods Results: Pigs instrumented coronary snares radiopaque markers within area at risk were randomized infarction-only (n = 10) or sMMPi (PGE-530742, 1 mg/kg TID) begun 3 days...
Although estrogen has effects on the heart, little is known regarding which genes in heart are directly responsive to estrogen. We have shown previously that lipoprotein lipase (LPL) expression was increased female hearts compared with male hearts. To test whether LPL gene regulated by estrogen, we perfused mouse from ovariectomized females 100 nM 17β-estradiol or vehicle for 2 h, after were frozen, and RNA isolated. The SYBR green real-time PCR method used detect expression. found addition...
The matrix metalloproteinases (MMPs), in particular, membrane type 1 MMP (MT1-MMP), are increased the context of myocardial ischemia and reperfusion (I/R) likely contribute to dysfunction. One potential upstream induction mechanism for MT1-MMP is endothelin (ET) release subsequent protein kinase C (PKC) activation. Modulation ET PKC signaling with respect activity I/R has yet be explored. Accordingly, this study examined vivo activation during following modification With use a novel...
LV myocardial remodeling is a structural hallmark of hypertensive hypertrophy, but molecular mechanisms driving this process are not well understood. The matrix metalloproteinases (MMPs) can cause in chronic disease states, how MMP activity altered with mechanical load remains unknown. present study quantified interstitial after discrete increase and dissected out the contributory role angiotensin II Type 1 receptor (AT R). Pigs (38kg) were randomized to undergo (1) increased by insertion an...
The coronavirus disease 2019 (COVID-19) pandemic demonstrated how rapidly vaccines and monoclonal antibodies (mAbs) could be deployed when the field is prepared to respond a novel virus, serving as proof of concept that prototype pathogen approach feasible. This success was built upon decades foundational research, including characterization protective antigens immunity leading development validation generalizable vaccine for multiple coronaviruses. For other virus families concern, less...