Dr. Rodriguez-Oquendo conducts basic science research in the area of lipid metabolism, with a particular emphasis on aspects of lipoprotein scavenger receptor class B type I (SR-BI) in atherosclerosis and infertility. In mice, deficiency of SR-BI is associated with higher HDL cholesterol levels, but paradoxically with increased risk for atherosclerosis and female infertility. Utilizing in vitro and ex vivo approaches Dr Rodriguez’s laboratory was the first to demonstrate that two human SR-BI gene (SCARB1) variants were significantly associated with subclinical atherosclerosis and incident cardiovascular disease in men and women, and with infertility in women. Since joining the University of Connecticut Health Center in 2012, Dr. Rodriguez-Oquendo has patented and licensed a novel blood biomarker for dysfunctional HDL cholesterol and other chronic inflammatory diseases. This novel patent has been licensed to Lipid Genomics, which is a company founded by Dr. Rodriguez-Oquendo. Lipid Genomics is now a member of the UConn Technology Incubator Program located at 400 Farmington Avenue. In October 2013 Dr Rodriguez-Oquendo was awarded Scientist-of-the-Year by Great Minds in STEM in recognition of her work in the area of genomic medicine and SCARB1. Dr. Rodriguez-Oquendo was recently recognized by the Connecticut Technology Council as a Woman of Innovation Research Innovation and Leadership, as well as by the American Heart Association with a Special Recognition Award.
Areas of Expertise (1)
The genetic link between healthy HDL cholesterol, heart disease, and infertility
New Jersey Medical School: M.D.
Rutgers College: B.A., Biology
Scientist of the Year (professional)
Awarded by Great Minds in STEM
Media Appearances (1)
How Good Is Good Cholesterol?
Discover magazine print
Open the freezer in the laboratory across the hall from Annabelle Rodriguez’s office at the University of Connecticut Health Center, and you will find rows of miniature fluid-filled vials, many of them holding tiny strands of DNA. For the past 13 years, Rodriguez, a physician-scientist in the university’s Center for Vascular Biology, has kept her eye on one particular gene in those DNA strands that is integral to the function of high-density lipoproteins (HDL)
Lymphocyte activation gene 3 and coronary artery disease.JCI Insight
2016 The lipoprotein scavenger receptor BI (SCARB1) rs10846744 noncoding variant is significantly associated with atherosclerotic disease independently of traditional cardiovascular risk factors. We identified a potentially novel connection between rs10846744, the immune checkpoint inhibitor lymphocyte activation gene 3 (LAG3), and atherosclerosis. METHODS: In vitro approaches included flow cytometry, lipid raft isolation, phosphosignaling, cytokine measurements, and overexpressing and silencing LAG3 protein. Fasting plasma LAG3 protein was measured in hyperalphalipoproteinemic (HALP) and Multi-Ethnic Study of Atherosclerosis (MESA) participants. RESULTS: In comparison with rs10846744 reference (GG homozygous) cells, LAG3 protein levels by flow cytometry (P < 0.001), in lipid rafts stimulated and unstimulated (P = 0.03), and phosphosignaling downstream of B cell receptor engagement of CD79A (P = 0.04), CD19 (P = 0.04), and LYN (P = 0.001) were lower in rs10846744 risk (CC homozygous) cells. Overexpressing LAG3 protein in risk cells and silencing LAG3 in reference cells confirmed its importance in phosphosignaling. Secretion of TNF-α was higher (P = 0.04) and IL-10 was lower (P = 0.04) in risk cells. Plasma LAG3 levels were lower in HALP carriers of the CC allele (P < 0.0001) and by race (P = 0.004). In MESA, race (P = 0.0005), age (P = 0.003), lipid medications (P = 0.03), smoking history (P < 0.0001), and rs10846744 genotype (P = 0.002) were independent predictors of plasma LAG3. In multivariable regression models, plasma LAG3 was significantly associated with HDL-cholesterol (HDL-C) (P = 0.007), plasma IL-10 (P < 0.0001), and provided additional predictive value above the Framingham risk score (P = 0.04). In MESA, when stratified by high HDL-C, plasma LAG3 was associated with coronary heart disease (CHD) (odds ratio 1.45, P = 0.004). CONCLUSION: Plasma LAG3 is a potentially novel independent predictor of HDL-C levels and CHD risk. FUNDING: This work was supported by an NIH RO1 grant (HL075646), the endowed Linda and David Roth Chair for Cardiovascular Research, and the Harold S. Geneen Charitable Trust Coronary Heart Disease Research award to Annabelle Rodriguez.
A Novel Anti-Inflammatory Effect for High Density Lipoprotein.PLoS One
2015 High density lipoprotein has anti-inflammatory effects in addition to mediating reverse cholesterol transport. While many of the chronic anti-inflammatory effects of high density lipoprotein (HDL) are attributed to changes in cell adhesion molecules, little is known about acute signal transduction events elicited by HDL in endothelial cells. We now show that high density lipoprotein decreases endothelial cell exocytosis, the first step in leukocyte trafficking. ApoA-I, a major apolipoprotein of HDL, mediates inhibition of endothelial cell exocytosis by interacting with endothelial scavenger receptor-BI which triggers an intracellular protective signaling cascade involving protein kinase C (PKC). Other apolipoproteins within the HDL particle have only modest effects upon endothelial exocytosis. Using a human primary culture of endothelial cells and murine apo-AI knockout mice, we show that apo-AI prevents endothelial cell exocytosis which limits leukocyte recruitment. These data suggest that high density lipoprotein may inhibit diseases associated with vascular inflammation in part by blocking endothelial exocytosis.
Association of the Lipoprotein Receptor SCARB1 Common Missense Variant rs4238001 with Incident Coronary Heart Disease.PLoS One
2015 Previous studies in mice and humans have implicated the lipoprotein receptor SCARB1 in association with atherosclerosis and lipid levels. In the current study, we sought to examine association of SCARB1 missense single nucleotide polymorphism (SNP) rs4238001 with incident coronary heart disease (CHD).
Chronic Intermittent Hypoxia Induces AtherosclerosisAmerican Journal of Respiratory and Critical Care Medicine
2007 Obstructive sleep apnea, a condition leading to chronic intermittent hypoxia (CIH), is associated with hyperlipidemia, atherosclerosis, and a high cardiovascular risk. A causal link between obstructive sleep apnea and atherosclerosis has not been established.
Aging, Androgens, and the Metabolic Syndrome in a Longitudinal Study of AgingThe Journal of Clinical Endrocrinology & Metabolism
2007 Based on Adult Treatment Panel III criteria, we previously reported that the prevalence of the metabolic syndrome (MS) increased with aging; was higher if elevated 2-h plasma postglucose challenge values were included as a criterion; and was greater in men, compared with women. The aim of this study was to evaluate the relationship between the MS and circulating androgen levels in a cohort of men in the Baltimore Longitudinal Study of Aging.