Research Overview
The Center hosts a diverse range of research programs whose central theme is an emphasis on extending basic research observations into clinical studies in the general areas of inflammation and preventive cardiovascular medicine. Some studies are aimed at defining novel inflammatory mediators of cardiovascular disease and their potential utility as diagnostic and prognostic indicators of risk, responses to therapies, or novel targets for therapeutic interventions. A further area of study is in understanding the role of intestinal micro flora in cardiometabolic diseases. Additional studies focus on the atheroprotective lipoprotein HDL and HDL-associated protein structure, function, and mechanisms for rendering HDL "dysfunctional".
Another major research effort focuses on genetic and molecular determinants of atherosclerotic plaque progression and vulnerability, including the role of structurally distinct oxidized phospholipids as inflammatory mediators of diverse disease processes. Research on platelet activating factor (PAF), PAF-like oxidized phospholipids, and catabolic pathways responsible for clearance of these lipidic inflammatory mediators, is ongoing. Complementary studies also focus on platelet function, mechanisms of hyperreactivity, and involvement in atherothrombotic disease. The role of oxidant stress, nitric oxide and alterations in arginine metabolism are being studied in the setting of myocardial dysfunction and atherosclerotic progression. Yet additional research studies focus on genetic determinants of cholesterol and fat absorption, dyslipidemia and the participation of lipid accumulation and apoptosis in hepatic pathophysiology. Finally, research efforts are also focused on defining the clinical utility of molecular markers of distinct oxidation pathways as quantitative indices of asthma presence, severity and response to therapy.
The Center is home to several core facilities designed to support human clinical trials laboratory research, including an accredited clinical reference laboratory and a mass spectrometry analytical laboratory. One of the Center's goals is to develop and validate novel diagnostic tests for cardiovascular and other inflammatory diseases. These tests are then made available for clinical trials use through the Preventive Research Lab (PRL).
Awarded Projects
Stanley L. Hazen, MD, PhD
Dr. Hazen's current research programs are:
- Role of gut flora in cardiometabolic diseases, Developing gut microbial TMA lyase inhibitors as cardiometabolic therapeutics, Role of myeloperoxidase in cardiovascular disease, HDL structure, function and dysfunction, Peroxidases and the origins of tissue injury in asthma, Molecular and genetic determinants of atherosclerotic plaque progression and vulnerability
Huang Y et al, J. Clin Invest. (2013) 123(9):3815
Wang, Z et al, Nature (2011) 472(7341):57
Wang, Z et al, Cell (2015) 163(7):1585
Zhu, W et al, Cell (2016) 165(1):111
J. Mark Brown, PhD
Dr. Brown's current research interests are:
- Mechanism Regulating Trans-Intestinal Cholesterol Excretion (TICE). We are currently probing mechanisms driving this novel pathway of reverse cholesterol transport, and testing novel therapeutics targeting this pathway for protection against atherosclerosis.
- Metaorganismal Endocrinology: Gut Microbe-Derived Hormones in Driving Cardiometabolic Disease. Here we are studying a metaorganismal endocrine axis by which gut microbial metabolism of nutrients common in high fat diets (phosphatidylcholine, choline, and L-carnitine) results in the production of novel microbe-derived hormones that impact obesity and insulin sensitivity in the host.
- Alpha Beta Hydrolase Domain (ABHD) Proteins in Metabolic Disease. These studies are uncovering novel roles for ABHD enzymes in the development of obesity, hepatic steatosis, type II diabetes, and cancer.
Leslie Cho, MD, FACC
Dr. Cho 's current research programs are:
- Novel biomarkers in coronary artery disease and peripheral artery disease Gender differences in cardiac disease and treatment, hyperlipdemia CoQ10 and statin intolerance, novel treatment for statin intolerance, predictors of heart disease, High fiber diet and inflammation Women and Cardiovascular disease and exercise effect on cardiac arrhythmias
Joseph DiDonato, PhD
Dr. DiDonato's current research programs are:
- Identifying molecular mechanisms of proinflammatory signaling by dysfunctional HDL, HDL structure, function and dysfunction, Using Genetic Code Expansion to identify the functional impact of specific sites of oxidative modification in apoA-I on dysfunctional HDL, Role of gut flora trimethylamine lyase activities in cardiometabolic diseases, Defining novel pathways of gut microbe-generated metabolite mediated platelet activation and thrombosis, Role of apoA-I's protective effect against tumorigenesis
Paul L. Fox, PhD
Dr. Fox's current research interests are:
- Translational control mechanisms regulating macrophage inflammation
- Site-selective protein S-nitrosylation in macrophages and cardiovascular disease
- Non-canonical activities of the glutamyl-prolyl tRNA synthetase in metabolism and inflammation
- A protein-directed RNA switch that regulates translation of VEGF-A mRNA in macrophages
- Mechanisms and regulation of programmed translational readthrough for proteome expansion
- Role of an antiangiogenic VEGF-A isoform in cancer
Thomas McIntyre, PhD
Dr. McIntyre's current research programs include:
- Defining the role of platelet EGF biology and activation
- Exploring platelet contribution to epithelium and tumor growth
- Defining lipid mediators in kidney function and damage
EGF augments thrombosis in damaged carotid arteries.
Edward Plow, PhD
Dr. Plow's current research programs are:
- Role of plasminogen and plasmin in inflammation and vascular biology
- Integrin adhesion receptors and their roles in cardiovascular diseases
- Mechanisms of cell adhesion and migration
- Thrombospondin-4 variants in cardiovascular disease
Jonathan D. Smith, PhD
Dr. Smith's current research interests are:
- Genetics of atherosclerosis susceptibility in mouse models
- Macrophage foam cell cholesterol metabolism and the role of autophagy in lipid droplet catabolism
- Macrophage inflammasome activation and its genetic regulation
- The mechanism of HDL biogenesis via ABCA1 and novel assays of HDL function
- HDL modification and dysfunction, and the use of a novel apoA1 variant that is resistant to becoming dysfunctional
- Functional genomics of human atrial fibrillation and the genetic control of gene expression in the human left atrium
M. Elaine Husni, MD, MPH
Dr. Husni's current research programs are:
- Identifying novel biomarkers of accelerated cardiovascular diseases in patients with systemic rheumatic diseases
- Establishing biorepository of rheumatology disease specific cohorts to study the molecular and genetic profiles of these patients to better understand the disease mechanism that contribute to disease and response to therapy
- Exploring mechanisms underlying accelerated atherosclerosis in patients with systemic rheumatic diseases
- Investigating the role of TNF receptor 2 as a novel therapeutic target of psoriatic diseases and its related comorbidities
W.H. Wilson Tang, MD
Dr. Tang's current research programs are concentrated in four Project areas:
- Cardio-Renal: Investigate the mechanistic underpinnings of and therapeutic strategies for the treatment and prevention of cardio-renal syndromes, TMAO/Gut Microbiota: Examine the contributions of gut microbiota and their metabolic pathways (e.g. TMAO) in the development and progression of cardiovascular and renal diseases, Cardiomyopathies: Investigate the molecular mechanisms leading to disease progression in specific cardiomyopathies; Heart Failure Network studies: Collaborate and participate in multicenter early phase clinical studies to identify novel therapies for heart failure in humans