Biography
The focus of our laboratory rests with exploring the influence of metabolic stress on accelerated atherosclerosis cardiovascular disease. Specifically, our interest is in how a protein called apolipoprotein E controls hematopoiesis through microRNA regulation to suppress atherosclerosis beyond its ability to lower plasma lipid levels.
A second interest of our laboratory explores how diabetic hyperglycemia contributes to differential microRNA biogenesis in mature immune cells and their progenitors. Specifically, we examine how this impacts on the release of these microRNAs into extracellular vesicles including exosomes to impact systemic and vascular inflammation and atherosclerosis.
Our goal is to develop engineered exosomes with defined microRNA cargo as new nanobiological effectors to control inflammation and atherosclerosis.
Education
Institution | Degree | Dept or School | End Date |
---|---|---|---|
University of Ottawa | Ph.D | Biochemistry | 05/1998 |
McGill University | B.S. | Biochemistry | 05/1990 |
In the News
May, 27, 2016 | Atherosclerosis Research Lab
Grants and Funding
- BLRD Research Career Scientist Award Application | NIH | 2021-04-01 - 2026-03-31 | Role: Principal Investigator
- P.R.I.S.M: Purification of exRNA by Immuno-capture and Sorting using Microfluidic | NIH | 2019-09-01 - 2023-08-31 | Role: Principal Investigator
- Exosomes in the Pathogenesis of Diabetic Atherosclerosis & its Treatment Opportunities | VA | 2019-07-01 - 2023-07-01 | Role: Principal Investigator
- Exosomes in the Pathogenesis of Diabetic Atherosclerosis & its Treatment Opportunities | NIH | 2019-07-01 - 2023-06-30 | Role: Principal Investigator
- P.R.I.S.M: Purification of exRNA by Immuno-capture and Sorting using Microfluidic | NIH | 2019-09-01 - 2021-08-31 | Role: Principal Investigator
- Hyperglycemia and MicroRNA Dysregulation of Inflammation in Atherosclerosis | NIH | 2016-06-01 - 2021-03-31 | Role: Principal Investigator
- Immune Modulation and Cardiac Remodeling | VA | 2016-10-01 - 2020-09-30 | Role: Co-Investigator
- In Vivo Regulated Release and Function of Extracellular Small RNAs | NIH/NCI | 2013-09-01 - 2018-08-31 | Role: Co-Investigator
- Hyperglycemia Dysregulation of MicroRNA in Myeloid Cells: Impact on Atherosclerosis Regression | American Heart Association | 2016-01-01 - 2017-12-31 | Role: Principal Investigator
- Does Diabetic Hyperglycemia Regulate Atherosclerosis Progression and Regression? | NIH | 2009-10-01 - 2014-06-30 | Role: Principal Investigator
- Role of apolipoprotein E4 in the progression and regression of atherosclerosis | NIH | 2007-09-26 - 2014-06-30 | Role: Principal Investigator
Publications
MOST RECENT PUBLICATIONS FROM A TOTAL OF 87
- Abstract A046: nSMase2-generated ceramide promotes PDA aggression through exosome reprogramming of the stroma.| | View in PubMed
- Exomap1 mouse: A transgenic model for in vivo studies of exosome biology.| | View in PubMed
- Polarized macrophages regulate fibro/adipogenic progenitor (FAP) adipogenesis through exosomes.| | View in PubMed
- ApoE enhances mitochondrial metabolism via microRNA-142a/146a-regulated circuits that suppress hematopoiesis and inflammation in hyperlipidemia.| | View in PubMed
- ApoE expression in macrophages communicates immunometabolic signaling that controls hyperlipidemia-driven hematopoiesis & inflammation via extracellular vesicles.| | View in PubMed
- Exomap1 mouse: a transgenic model for in vivo studies of exosome biology.| | View in PubMed
- exRNA-eCLIP intersection analysis reveals a map of extracellular RNA binding proteins and associated RNAs across major human biofluids and carriers.| | View in PubMed
- Patients with abdominal aortic aneurysms have reduced levels of microRNA 122-5p in circulating exosomes.| | View in PubMed
- Current challenges and future directions for engineering extracellular vesicles for heart, lung, blood and sleep diseases.| | View in PubMed
- MetfOrmin BenefIts Lower Extremities with Intermittent Claudication (MOBILE IC): randomized clinical trial protocol.| | View in PubMed
- Abstract C051: Ceramide signaling regulates PDA aggression through exosome reprogramming of the stroma.| | View in PubMed
- Poster 155: Muscle-Derived Beige Adipose Precursors Secrete Promyogenic Exosomes that Treat Rotator Cuff Muscle Degeneration in Mice and are Identified in Humans by Single-Cell RNA Sequencing.| | View in PubMed
- Phase 2 of extracellular RNA communication consortium charts next-generation approaches for extracellular RNA research.| | View in PubMed
- Muscle-Derived Beige Adipose Precursors Secrete Promyogenic Exosomes That Treat Rotator Cuff Muscle Degeneration in Mice and Are Identified in Humans by Single-Cell RNA Sequencing.| | View in PubMed
- IL-4 polarized human macrophage exosomes control cardiometabolic inflammation and diabetes in obesity.| | View in PubMed
- Visualizing transfer of microbial biomolecules by outer membrane vesicles in microbe-host-communication in vivo.| | View in PubMed
- High glucose macrophage exosomes enhance atherosclerosis by driving cellular proliferation & hematopoiesis.| | View in PubMed
- M2 macrophage exosomes regulate hematopoiesis & resolve inflammation in atherosclerosis via microrna cargo.| | View in PubMed
- Abstract 15839: Patients With Abdominal Aortic Aneurysms Have Reduced Levels of MicroRNA 122-5p in Circulating Exosomes.| | View in PubMed
- Abstract 17293: Hyperglycemia Enhances Pro-Inflammatory Properties of Macrophage-Derived Exosomes to Drive Hematopoiesis in Apolipoprotein E-Deficient Mouse.| | View in PubMed
- Correction: Cushioned-Density Gradient Ultracentrifugation (C-DGUC) improves the isolation efficiency of extracellular vesicles.| | View in PubMed
- Macrophage Exosomes Resolve Atherosclerosis by Regulating Hematopoiesis and Inflammation via MicroRNA Cargo.| | View in PubMed
- Circulating exosomes from patients with peripheral artery disease influence vascular cell migration and contain distinct microRNA cargo.| | View in PubMed
- Abstract C20: Smpd3 augments chemotherapy and thwarts PDA progression.| | View in PubMed
- Cushioned-Density Gradient Ultracentrifugation (C-DGUC) improves the isolation efficiency of extracellular vesicles.| | View in PubMed
- Female mice with apolipoprotein E4 domain interaction demonstrated impairments in spatial learning and memory performance and disruption of hippocampal cyto-architecture.| | View in PubMed
- Small RNA Sequencing across Diverse Biofluids Identifies Optimal Methods for exRNA Isolation.| | View in PubMed
- The Extracellular RNA Communication Consortium: Establishing Foundational Knowledge and Technologies for Extracellular RNA Research.| | View in PubMed
- exRNA Atlas Analysis Reveals Distinct Extracellular RNA Cargo Types and Their Carriers Present across Human Biofluids.| | View in PubMed
- Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines.| | View in PubMed
- MicroRNA-146a & hematopoiesis: friend or foe in atherosclerosis.| | View in PubMed
- Apolipoprotein E and Atherosclerosis: From Lipoprotein Metabolism to MicroRNA Control of Inflammation.| | View in PubMed
- Abstract 184: Hyperglycemia Enhances Pro-inflammatory Properties of Macrophage-derived Exosomes to Drive Hematopoiesis in Apolipoprotein E-deficient Mouse.| | View in PubMed
- Abstract 262: Circulating Exosomes from PAD Patients Modulate Vascular Repair and Inflammation.| | View in PubMed
- Abstract 408: ApoE Regulation of Hematopoiesis Suppresses Atherosclerosis by Reducing Adaptive Immunity in Hyperlipidemic Mice.| | View in PubMed
- Abstract 443: Cushioned-Density Gradient Ultracentrifugation (C-DGUC) Improves the Isolation Efficiency of Exosomes for their use in Atherosclerosis Research.| | View in PubMed
- Advances, challenges, and opportunities in extracellular RNA biology: insights from the NIH exRNA Strategic Workshop.| | View in PubMed
- Cushioned-Density Gradient Ultracentrifugation (C-DGUC): A Refined and High Performance Method for the Isolation, Characterization, and Use of Exosomes.| | View in PubMed
- Isolation of Plasma Lipoproteins as a Source of Extracellular RNA.| | View in PubMed
- Therapeutic control of systemic inflammation & atherosclerosis with ApoE-polarized macrophage exosomes.| | View in PubMed
- Hyperpolarized 13 C magnetic resonance evaluation of renal ischemia reperfusion injury in a murine model.| | View in PubMed
- An intracellular matrix metalloproteinase-2 isoform induces tubular regulated necrosis: implications for acute kidney injury.| | View in PubMed
- Extending gene ontology in the context of extracellular RNA and vesicle communication.| | View in PubMed
- Inhibition of p38 Mitogen-Activated Protein Kinase Enhances the Apoptosis Induced by Oxidized Low-Density Lipoprotein in Endothelial Progenitor Cells.| | View in PubMed
- Immunosuppression With FTY720 Reverses Cardiac Dysfunction in Hypomorphic ApoE Mice Deficient in SR-BI Expression That Survive Myocardial Infarction Caused by Coronary Atherosclerosis.| | View in PubMed
- Abstract 17311: Molecular Memory and the Epigenetic Regulation of Cardiac Intracellular Matrix Metalloproteinase-2.| | View in PubMed
- Biogenesis, delivery, and function of extracellular RNA.| | View in PubMed
- Meeting report: discussions and preliminary findings on extracellular RNA measurement methods from laboratories in the NIH Extracellular RNA Communication Consortium.| | View in PubMed
- Apolipoprotein e e4 domain interaction in size of hippocampal subregions, density of newborn neurons, and cognitive behaviors.| | View in PubMed
- Abstract 155: MicroRNA-146a Suppression of NF-?B-driven Monocyte/Macrophage Activation and Atherosclerosis is Regulated by Cellular ApoE Expression.| | View in PubMed
- Abstract 23: Immunosuppression with FTY720 Reverses Cardiac Dysfunction to Prevent Chronic Heart Failure in Mice that Survive Diet-induced Myocardial Infarction.| | View in PubMed
- Abstract 481: Diabetic Hyperglycemia Accelerates Atherosclerosis by Driving Adaptive Immunity in Mice with Similar Hyperlipidemia.| | View in PubMed
- Apolipoprotein E enhances microRNA-146a in monocytes and macrophages to suppress nuclear factor-κB-driven inflammation and atherosclerosis.| | View in PubMed
- Apolipoprotein E and Atherosclerosis: Beyond Lipid Effects.| | View in PubMed
- A screen in mice uncovers repression of lipoprotein lipase by microRNA-29a as a mechanism for lipid distribution away from the liver.| | View in PubMed
- The immunosuppressant FTY720 prolongs survival in a mouse model of diet-induced coronary atherosclerosis and myocardial infarction.| | View in PubMed
- Hyperglycemia impairs atherosclerosis regression in mice.| | View in PubMed
- N-terminal truncated intracellular matrix metalloproteinase-2 induces cardiomyocyte hypertrophy, inflammation and systolic heart failure.| | View in PubMed
- Inducible ApoE gene repair in hypomorphic ApoE mice deficient in the low-density lipoprotein receptor promotes atheroma stabilization with a human-like lipoprotein profile.| | View in PubMed
- Abstract 195: Apolipoprotein E Suppresses Atherosclerosis by Reducing Th1 Inflammatory Responses and by Favorably Altering Aortic Dendritic Cell Subsets in Hyperlipidemic Mice.| | View in PubMed
- Abstract 375: Inducible ApoE Gene Repair in HypoE Mice Deficient in the LDL Receptor Promotes Atheroma Stabilization with a Human-like Lipoprotein Profile.| | View in PubMed
- Abstract 552: The Immunosuppressant FTY720 Increases Longevity and Prevents Chronic Heart Failure in HypoE Mice Deficient in the SR-BI Receptor that Survive Myocardial Infarction Caused by Diet-induced Coronary Atherosclerosis.| | View in PubMed
- Apolipoprotein E regulation of myeloid cell plasticity in atherosclerosis.| | View in PubMed
- Macrophage-specific apoE gene repair reduces diet-induced hyperlipidemia and atherosclerosis in hypomorphic Apoe mice.| | View in PubMed
- A novel intracellular isoform of matrix metalloproteinase-2 induced by oxidative stress activates innate immunity.| | View in PubMed
- Apolipoprotein E4 domain interaction accelerates diet-induced atherosclerosis in hypomorphic Arg-61 apoe mice.| | View in PubMed
- ApoE suppresses atherosclerosis by reducing lipid accumulation in circulating monocytes and the expression of inflammatory molecules on monocytes and vascular endothelium.| | View in PubMed
- Oxidized low-density lipoprotein induces apoptosis in endothelial progenitor cells by inactivating the phosphoinositide 3-kinase/Akt pathway.| | View in PubMed
- Apolipoprotein E Suppresses Atherosclerosis by Reducing Leukocyte Recruitment to Atheroma.| | View in PubMed
- Heparin Protects Against Septic Mortality via Apoe-Antagonism.| | View in PubMed
- High-density lipoprotein determines adult mouse cardiomyocyte fate after hypoxia-reoxygenation through lipoprotein-associated sphingosine 1-phosphate.| | View in PubMed
- Diet-induced occlusive coronary atherosclerosis, myocardial infarction, cardiac dysfunction, and premature death in scavenger receptor class B type I-deficient, hypomorphic apolipoprotein ER61 mice.| | View in PubMed
- VEGF is crucial for the hepatic vascular development required for lipoprotein uptake.| | View in PubMed
- Apolipoprotein E promotes the regression of atherosclerosis independently of lowering plasma cholesterol levels.| | View in PubMed
- Antibody phenotyping test for the human apolipoprotein E2 isoform.| | View in PubMed
- Cholesterol: from heart attacks to Alzheimer's disease.| | View in PubMed
- Hepatocyte-derived ApoE is more effective than non-hepatocyte-derived ApoE in remnant lipoprotein clearance.| | View in PubMed
- 3P-0878 A mouse model to study the role of ApoE in atherosclerosis regression and plaque vulnerability in peripheral arterial disease.| | View in PubMed
- Hypomorphic apolipoprotein E mice: a new model of conditional gene repair to examine apolipoprotein E-mediated metabolism.| | View in PubMed
- Periplasmic expression and purification of recombinant Fabs.| | View in PubMed
- Introduction of human apolipoprotein E4 "domain interaction" into mouse apolipoprotein E.| | View in PubMed
- New insights into the heparan sulfate proteoglycan-binding activity of apolipoprotein E.| | View in PubMed
- Binding of an antibody mimetic of the human low density lipoprotein receptor to apolipoprotein E is governed through electrostatic forces. Studies using site-directed mutagenesis and molecular modeling.| | View in PubMed
- Bacterial expression and purification of the Fab fragment of a monoclonal antibody specific for the low-density lipoprotein receptor-binding site of human apolipoprotein E.| | View in PubMed
- Structure of a monoclonal 2E8 Fab antibody fragment specific for the low-density lipoprotein-receptor binding region of apolipoprotein E refined at 1.9 A.| | View in PubMed
- Molecular characterization of two monoclonal antibodies specific for the LDL receptor-binding site of human apolipoprotein E.| | View in PubMed
- Determination of the fine specificity and molecular cloning of two monoclonal antibodies directed against the receptor-binding domain of human apolipoprotein E.| | View in PubMed