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.
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 92
- Comparison of EV characterization by commercial high-sensitivity flow cytometers and a custom single-molecule flow cytometer.| | PubMed
- Label-free single-vesicle based surface enhanced Raman spectroscopy: A robust approach for investigating the biomolecular composition of small extracellular vesicles.| | PubMed
- Abstract 3047: Extracellular Vesicles Produced By IL4-polarized Human Macrophages Suppress Atherosclerosis By Reprograming Ly6c hi Monocytes.| | UCSF Research Profile
- The EV antibody database: An interactive database of curated antibodies for extracellular vesicle and nanoparticle research.| | PubMed
- Abstract A046: nSMase2-generated ceramide promotes PDA aggression through exosome reprogramming of the stroma.| | UCSF Research Profile
- Exomap1 mouse: A transgenic model for in vivo studies of exosome biology.| | UCSF Research Profile
- Polarized macrophages regulate fibro/adipogenic progenitor (FAP) adipogenesis through exosomes.| | PubMed
- ApoE enhances mitochondrial metabolism via microRNA-142a/146a-regulated circuits that suppress hematopoiesis and inflammation in hyperlipidemia.| | PubMed
- Abstract P3167: Identification Of Macrophage-specific Markers On Extracellular Vesicles In A Transgenic Mouse Model And Humans.| | UCSF Research Profile
- ApoE expression in macrophages communicates immunometabolic signaling that controls hyperlipidemia-driven hematopoiesis & inflammation via extracellular vesicles.| | PubMed
- Exomap1 mouse: a transgenic model for in vivo studies of exosome biology.| | PubMed
- exRNA-eCLIP intersection analysis reveals a map of extracellular RNA binding proteins and associated RNAs across major human biofluids and carriers.| | PubMed
- Patients with abdominal aortic aneurysms have reduced levels of microRNA 122-5p in circulating exosomes.| | PubMed
- Current challenges and future directions for engineering extracellular vesicles for heart, lung, blood and sleep diseases.| | PubMed
- MetfOrmin BenefIts Lower Extremities with Intermittent Claudication (MOBILE IC): randomized clinical trial protocol.| | PubMed
- Abstract C051: Ceramide signaling regulates PDA aggression through exosome reprogramming of the stroma.| | UCSF Research Profile
- 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.| | UCSF Research Profile
- Phase 2 of extracellular RNA communication consortium charts next-generation approaches for extracellular RNA research.| | 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.| | PubMed
- IL-4 polarized human macrophage exosomes control cardiometabolic inflammation and diabetes in obesity.| | PubMed
- Visualizing transfer of microbial biomolecules by outer membrane vesicles in microbe-host-communication in vivo.| | PubMed
- High glucose macrophage exosomes enhance atherosclerosis by driving cellular proliferation & hematopoiesis.| | PubMed
- M2 macrophage exosomes regulate hematopoiesis & resolve inflammation in atherosclerosis via microrna cargo.| | UCSF Research Profile
- Abstract 15839: Patients With Abdominal Aortic Aneurysms Have Reduced Levels of MicroRNA 122-5p in Circulating Exosomes.| | UCSF Research Profile
- Abstract 17293: Hyperglycemia Enhances Pro-Inflammatory Properties of Macrophage-Derived Exosomes to Drive Hematopoiesis in Apolipoprotein E-Deficient Mouse.| | UCSF Research Profile
- Correction: Cushioned-Density Gradient Ultracentrifugation (C-DGUC) improves the isolation efficiency of extracellular vesicles.| | PubMed
- Macrophage Exosomes Resolve Atherosclerosis by Regulating Hematopoiesis and Inflammation via MicroRNA Cargo.| | PubMed
- Circulating exosomes from patients with peripheral artery disease influence vascular cell migration and contain distinct microRNA cargo.| | PubMed
- Abstract C20: Smpd3 augments chemotherapy and thwarts PDA progression.| | UCSF Research Profile
- Cushioned-Density Gradient Ultracentrifugation (C-DGUC) improves the isolation efficiency of extracellular vesicles.| | PubMed
- Female mice with apolipoprotein E4 domain interaction demonstrated impairments in spatial learning and memory performance and disruption of hippocampal cyto-architecture.| | PubMed
- Small RNA Sequencing across Diverse Biofluids Identifies Optimal Methods for exRNA Isolation.| | PubMed
- The Extracellular RNA Communication Consortium: Establishing Foundational Knowledge and Technologies for Extracellular RNA Research.| | PubMed
- exRNA Atlas Analysis Reveals Distinct Extracellular RNA Cargo Types and Their Carriers Present across Human Biofluids.| | 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.| | PubMed
- MicroRNA-146a & hematopoiesis: friend or foe in atherosclerosis.| | PubMed
- Apolipoprotein E and Atherosclerosis: From Lipoprotein Metabolism to MicroRNA Control of Inflammation.| | PubMed
- Abstract 184: Hyperglycemia Enhances Pro-inflammatory Properties of Macrophage-derived Exosomes to Drive Hematopoiesis in Apolipoprotein E-deficient Mouse.| | UCSF Research Profile
- Abstract 262: Circulating Exosomes from PAD Patients Modulate Vascular Repair and Inflammation.| | UCSF Research Profile
- Abstract 408: ApoE Regulation of Hematopoiesis Suppresses Atherosclerosis by Reducing Adaptive Immunity in Hyperlipidemic Mice.| | UCSF Research Profile
- Abstract 443: Cushioned-Density Gradient Ultracentrifugation (C-DGUC) Improves the Isolation Efficiency of Exosomes for their use in Atherosclerosis Research.| | UCSF Research Profile
- Advances, challenges, and opportunities in extracellular RNA biology: insights from the NIH exRNA Strategic Workshop.| | PubMed
- Cushioned-Density Gradient Ultracentrifugation (C-DGUC): A Refined and High Performance Method for the Isolation, Characterization, and Use of Exosomes.| | PubMed
- Isolation of Plasma Lipoproteins as a Source of Extracellular RNA.| | PubMed
- Therapeutic control of systemic inflammation & atherosclerosis with ApoE-polarized macrophage exosomes.| | UCSF Research Profile
- Hyperpolarized 13 C magnetic resonance evaluation of renal ischemia reperfusion injury in a murine model.| | PubMed
- An intracellular matrix metalloproteinase-2 isoform induces tubular regulated necrosis: implications for acute kidney injury.| | PubMed
- Extending gene ontology in the context of extracellular RNA and vesicle communication.| | PubMed
- Inhibition of p38 Mitogen-Activated Protein Kinase Enhances the Apoptosis Induced by Oxidized Low-Density Lipoprotein in Endothelial Progenitor Cells.| | PubMed
- Immunosuppression With FTY720 Reverses Cardiac Dysfunction in Hypomorphic ApoE Mice Deficient in SR-BI Expression That Survive Myocardial Infarction Caused by Coronary Atherosclerosis.| | PubMed
- Abstract 17311: Molecular Memory and the Epigenetic Regulation of Cardiac Intracellular Matrix Metalloproteinase-2.| | UCSF Research Profile
- Biogenesis, delivery, and function of extracellular RNA.| | PubMed
- Meeting report: discussions and preliminary findings on extracellular RNA measurement methods from laboratories in the NIH Extracellular RNA Communication Consortium.| | PubMed
- Apolipoprotein e e4 domain interaction in size of hippocampal subregions, density of newborn neurons, and cognitive behaviors.| | UCSF Research Profile
- Abstract 155: MicroRNA-146a Suppression of NF-?B-driven Monocyte/Macrophage Activation and Atherosclerosis is Regulated by Cellular ApoE Expression.| | UCSF Research Profile
- Abstract 23: Immunosuppression with FTY720 Reverses Cardiac Dysfunction to Prevent Chronic Heart Failure in Mice that Survive Diet-induced Myocardial Infarction.| | UCSF Research Profile
- Abstract 481: Diabetic Hyperglycemia Accelerates Atherosclerosis by Driving Adaptive Immunity in Mice with Similar Hyperlipidemia.| | UCSF Research Profile
- Apolipoprotein E enhances microRNA-146a in monocytes and macrophages to suppress nuclear factor-κB-driven inflammation and atherosclerosis.| | PubMed
- Apolipoprotein E and Atherosclerosis: Beyond Lipid Effects.| | UCSF Research Profile
- A screen in mice uncovers repression of lipoprotein lipase by microRNA-29a as a mechanism for lipid distribution away from the liver.| | PubMed
- The immunosuppressant FTY720 prolongs survival in a mouse model of diet-induced coronary atherosclerosis and myocardial infarction.| | PubMed
- Hyperglycemia impairs atherosclerosis regression in mice.| | PubMed
- N-terminal truncated intracellular matrix metalloproteinase-2 induces cardiomyocyte hypertrophy, inflammation and systolic heart failure.| | 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.| | PubMed
- Abstract 195: Apolipoprotein E Suppresses Atherosclerosis by Reducing Th1 Inflammatory Responses and by Favorably Altering Aortic Dendritic Cell Subsets in Hyperlipidemic Mice.| | UCSF Research Profile
- Abstract 375: Inducible ApoE Gene Repair in HypoE Mice Deficient in the LDL Receptor Promotes Atheroma Stabilization with a Human-like Lipoprotein Profile.| | UCSF Research Profile
- 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.| | UCSF Research Profile
- Apolipoprotein E regulation of myeloid cell plasticity in atherosclerosis.| | PubMed
- Macrophage-specific apoE gene repair reduces diet-induced hyperlipidemia and atherosclerosis in hypomorphic Apoe mice.| | PubMed
- A novel intracellular isoform of matrix metalloproteinase-2 induced by oxidative stress activates innate immunity.| | PubMed
- Apolipoprotein E4 domain interaction accelerates diet-induced atherosclerosis in hypomorphic Arg-61 apoe mice.| | PubMed
- ApoE suppresses atherosclerosis by reducing lipid accumulation in circulating monocytes and the expression of inflammatory molecules on monocytes and vascular endothelium.| | PubMed
- Oxidized low-density lipoprotein induces apoptosis in endothelial progenitor cells by inactivating the phosphoinositide 3-kinase/Akt pathway.| | PubMed
- Apolipoprotein E Suppresses Atherosclerosis by Reducing Leukocyte Recruitment to Atheroma.| | UCSF Research Profile
- Heparin Protects Against Septic Mortality via Apoe-Antagonism.| | UCSF Research Profile
- High-density lipoprotein determines adult mouse cardiomyocyte fate after hypoxia-reoxygenation through lipoprotein-associated sphingosine 1-phosphate.| | 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.| | PubMed
- VEGF is crucial for the hepatic vascular development required for lipoprotein uptake.| | PubMed
- Apolipoprotein E promotes the regression of atherosclerosis independently of lowering plasma cholesterol levels.| | PubMed
- Antibody phenotyping test for the human apolipoprotein E2 isoform.| | PubMed
- Cholesterol: from heart attacks to Alzheimer's disease.| | PubMed
- Hepatocyte-derived ApoE is more effective than non-hepatocyte-derived ApoE in remnant lipoprotein clearance.| | PubMed
- 3P-0878 A mouse model to study the role of ApoE in atherosclerosis regression and plaque vulnerability in peripheral arterial disease.| | UCSF Research Profile
- Hypomorphic apolipoprotein E mice: a new model of conditional gene repair to examine apolipoprotein E-mediated metabolism.| | PubMed
- Periplasmic expression and purification of recombinant Fabs.| | PubMed
- Introduction of human apolipoprotein E4 "domain interaction" into mouse apolipoprotein E.| | PubMed
- New insights into the heparan sulfate proteoglycan-binding activity of apolipoprotein E.| | 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.| | 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.| | 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.| | PubMed
- Molecular characterization of two monoclonal antibodies specific for the LDL receptor-binding site of human apolipoprotein E.| | PubMed
- Determination of the fine specificity and molecular cloning of two monoclonal antibodies directed against the receptor-binding domain of human apolipoprotein E.| | UCSF Research Profile