Nathalie Pamir, Ph.D.
- Associate Professor of Medicine, Division of Cardiovascular Medicine, School of Medicine
- Associate Professor of Biochemistry and Molecular Biology, School of Medicine
- Program in Molecular and Cellular Biosciences, School of Medicine
Biography
On the cholesterol front, we want to know: Is good HDL really good? If so, why? Or have we found a way through our lifestyle to make it bad so it’s no longer working? We do know that HDL levels have a hereditary component; roughly 50% is unchangeable. So you can only modify the remaining 50%. You can think of HDL particles as tiny balls, about one thousandth the size of a cell nucleus, infiltrating every tissue in the body, removing cholesterol from cells and bringing it back to the liver. That’s their job. Historically we always cared about the number of “balls” but that’s now considered irrelevant because so many studies have shown that raising HDL levels does not necessarily provide cardiovascular benefits.
The discussion now is around how efficient, how good these particles are at removing cholesterol from cells and bringing it back to the liver. Testing for function isn’t at the clinical level yet but there are four large epidemiology studies looking at HDL function and cardiovascular risk. What I want to know is the function genetically regulated? If so, what’s the wiggle room for improvement? I currently have an American Heart Association Scientist Development Grant to look at HDL proteome (a set of proteins expressed) and function across hundreds of strains of mice. I’m using a genetic tool developed by UCLA that allows you to map a phenotypic trait, say HDL function, and then identify a couple of genes that associate with that trait – so, these genes regulate that trait. In my studies I’ve shown that HDL function and HDL proteome are genetically regulated. The most amazing part is that just by looking at the HDL proteome of 80 to 100 proteins, you can predict the genealogy of a trait with statistical analysis.
Another interesting area I’m exploring is we know HDL function correlates with CVD but in most cases, it’s not the CVD that kills you, it’s a stroke event. But why? The relationship between HDL cholesterol and stroke is not very well defined. So I’m working with Nabil Alkayed, M.D., Ph.D., director of the Division of Cerebrovascular Research in the OHSU School of Medicine to better understand this link. We tested 15 patients and found a tremendous difference not only in HDL function but also in the HDL proteome. The reason that’s important is we believe protein dictates function. If we understand what these HDL “balls” are made of protein-wise then maybe we can understand why they’re good at, or failing, at their function. Sergio Fazio M.D., Ph.D., head of preventive cardiology introduced me to REGARDS (Reasons for Geographic and Racial Differences in Stroke) researchers and I’ve been granted access to samples from this large epidemiology study to further explore this research question. I have 3,000 samples total – 1,000 healthy, 1,000 CVD, and 1,000 stroke to look at HDL biology, function, proteome, and genetics. Now I need to do the science and have requested funding from NIH.
Education and training
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Degrees
- M.Sc., 2002, University of British Columbia
- Ph.D., 2009, University of Washington
Memberships and associations:
- AHA
Areas of interest
- Brigding the gap between the discovery of new metrics of High Density Lipoprotein (HDL) and their application in clinique
- Understanding the relationship between high density lipoprotein and stroke
- Understanding the molecular mechanisms for the relationship between epicardial adipose depot and heart disease
- Defining preserved -etnicity dependent signatures of HDL proteome in populations .
Honors and awards
- Top Student Award, University Of Washgington School of Public Health
- AHA Postdoctoral Fellowship
- AHA Scientist Development Grant
Publications
Publications
Fish Oil Supplementation Modifies the Proteome, Lipidome, and Function of High-Density Lipoprotein
Journal of NutritionEffect of antiplatelet agents and tyrosine kinase inhibitors on oxLDL-mediated procoagulant platelet activity
Blood AdvancesLow-density lipoprotein promotes microvascular thrombosis by enhancing von Willebrand factor self-association
BloodA method for lipoprotein (a) Isolation from a small volume of plasma with applications for clinical research
Scientific ReportsCollaborative Cohort of Cohorts for COVID-19 Research (C4R) Study
American journal of epidemiologyRace-Dependent Association of High-Density Lipoprotein Cholesterol Levels With Incident Coronary Artery Disease
Journal of the American College of CardiologyMacrophage Receptor-Related LRP1Protein (Low-Density 1) Is Required Lipoprotein for the Effect of CD47 Blockade on Efferocytosis and Atherogenesis—Brief Report
Arteriosclerosis, thrombosis, and vascular biologyHealth care experiences during the COVID-19 pandemic by race and social determinants of health among adults age ≥ 58 years in the REGARDS study
BMC public healthHepatic Sensing Loop Regulates PCSK9 Secretion in Response to Inhibitory Antibodies
Journal of the American College of CardiologyHigh triglyceride to HDL cholesterol ratio is associated with increased coronary heart disease among White but not Black adults
American Journal of Preventive CardiologyInsights into the kinetics and dynamics of the furin-cleaved form of PCSK9
Journal of lipid researchRole of PAI-1 in hepatic steatosis and dyslipidemia
Scientific ReportsUse of commercial genetic testing to help reclassify LDL receptor variants in clinical practice
Journal of clinical lipidologyHigh-Density Lipoprotein Carries Markers That Track with Recovery from Stroke
Circulation researchMicroRNA-144 Silencing Protects Against Atherosclerosis in Male, but Not Female Mice
Arteriosclerosis, thrombosis, and vascular biologyElevated Lipoprotein(a) Levels Lower ABCA1 Cholesterol Efflux Capacity
Journal of Clinical Endocrinology and MetabolismGenetic control of the mouse HDL proteome defines HDL traits, function, and heterogeneity
Journal of lipid researchAPOL1 Nephropathy Risk Variants and Incident Cardiovascular Disease Events in Community-Dwelling Black Adults
Circulation. Genomic and precision medicineGM-CSF driven myeloid cells in adipose tissue link weight gain and insulin resistance via formation of 2-aminoadipate
Scientific ReportsExtended multiplexing of tandem mass tags (TMT) labeling reveals age and high fat diet specific proteome changes in mouse epididymal adipose tissue
Molecular and Cellular ProteomicsPlasminogen promotes cholesterol efflux by the ABCA1 pathway
JCI InsightProteomic analysis of HDL from inbred mouse strains implicates APOE associated with HDL in reduced cholesterol efflux capacity via the ABCA1 pathway
Journal of lipid researchGranulocyte/macrophage colony-stimulating factor-dependent dendritic cells restrain lean adipose tissue expansion
Journal of Biological ChemistryParallel reaction monitoring (PRM) and selected reaction monitoring (SRM) exhibit comparable linearity, dynamic range and precision for targeted quantitative HDL proteomics
Journal of ProteomicsMacrophage metalloelastase (MMP12) regulates adipose tissue expansion, insulin sensitivity, and expression of inducible nitric oxide synthase
EndocrinologyQuantification of HDL particle concentration by calibrated ion mobility analysis
Clinical chemistryDeficiency of lymphotoxin-a does not exacerbate high-fat diet-induced obesity but does enhance inflammation in mice
American Journal of Physiology - Endocrinology and Metabolism