Health Research Center
Lipoprotein Metabolism, Scavenger Receptors, Cardiovascular Disease, Diabetes, ObesityView Daisy Sahoo, PhD Bio
The role of scavenger receptors in cardiovascular disease and related metabolic disorders.
Atherosclerosis is a disease caused by plaque build-up in the artery wall, which ultimately results in reduced blood flow due to narrowing of the arteries. Plaque build-up results from the accumulation of cholesterol and other cellular debris. Cholesterol is carried through our bloodstream in vehicles called lipoproteins. Low density lipoproteins (LDL) – the “bad cholesterol” – carry cholesterol from the liver to peripheral tissues (such as the arterial wall). High density lipoproteins (HDL) – the “good cholesterol” – transport cholesterol from peripheral tissues back to the liver for excretion in a process called “reverse cholesterol transport.”
While HDL protects against atherosclerosis due to its role in reducing oxidative damage, preventing inflammation and promoting endothelial function, our lab is very interested in the role that HDL plays in reverse cholesterol transport and whole body cholesterol disposal.
Scavenger receptor class B type I (SR-BI), the most physiologically relevant HDL receptor, is highly expressed in the liver and plays a key role in mediating the delivery of HDL-C to the liver for excretion. Genetic mouse models demonstrate that SR-BI protects against atherosclerosis. Further, the recent discovery of SR-BI mutations in patients with high HDL-C levels strongly supports a critical role of SR-BI in facilitating the flux of cholesterol out of the body.
In order to develop novel therapeutic strategies that treat hypercholesterolemia and its associated pathologies such as atherosclerosis, it is critical that we understand the mechanisms that regulate receptor-ligand interactions at the end of reverse cholesterol transport. A better understanding of the interaction between SR-BI and HDL will allow us to gain novel insight into mechanisms that facilitate the efficient clearance of HDL-C via SR-BI-mediated selective uptake of HDL lipids.
Our laboratory is trying to answer the following questions:
- What are key structural features of SR-BI that facilitate HDL-cholesterol transport?
- Can we use biophysical and high-resolution techniques to gain structural information about full-length SR-BI and/or its extracellular/transmembrane domains?
- What is the oligomeric organization of SR-BI and how does that influence HDL-cholesterol transport?
- How does oxidation of HDL impact its cardio-protective functions and the progression of atherosclerosis?
- How does SR-BI facilitate cholesterol delivery into adipocytes?
- What happens when HDL-cholesterol gets hydrolyzed in cells?
- How does HDL impact beta cell function and diabetes?
Research in the Sahoo laboratory relies on several techniques that will teach the following:
- Cell culture-based cholesterol transport assays
- Lipid and lipoprotein analyses
- Signal transduction
- Protein-protein interactions using biophysical/biochemical methods
- Fluorescence methodologies (e.g. spin labeling, FRET)
- Live cell imaging
- Confocal microscopy
- Mass Spectrometry (via collaboration)
- NMR (via collaboration)
- EPR (via collaboration)
- In vivo mouse models that express SR-BI mutants
- In vivo reverse cholesterol transport and atherosclerosis studies
(Powers HR, Sahoo D.) Curr Atheroscler Rep. 2022 Apr;24(4):277-288 PMID: 35107765 PMCID: PMC8809234 SCOPUS ID: 2-s2.0-85124168322 02/03/2022
(Xu H, Thomas MJ, Kaul S, Kallinger R, Ouweneel AB, Maruko E, Oussaada SM, Jongejan A, Cense HA, Nieuwdorp M, Serlie MJ, Goldberg IJ, Civelek M, Parks BW, Lusis AJ, Knaack D, Schill RL, May SC, Reho JJ, Grobe JL, Gantner B, Sahoo D, Sorci-Thomas MG.) Arterioscler Thromb Vasc Biol. 2021 11;41(11):2708-2725 PMID: 34551590 PMCID: PMC8551036 SCOPUS ID: 2-s2.0-85118592107 09/24/2021
(Aurubin CA, Knaack DA, Sahoo D, Tarakanova VL.) J Virol. 2021 08 10;95(17):e0064921 PMID: 34105999 PMCID: PMC8354329 SCOPUS ID: 2-s2.0-85112335753 06/10/2021
(Stuttgen GM, Sahoo D.) Endocrinology. 2021 08 01;162(8) PMID: 34043793 PMCID: PMC8218936 SCOPUS ID: 2-s2.0-85109115515 05/28/2021
(May SC, Sahoo D.) Annals of Blood. December 2021;6 SCOPUS ID: 2-s2.0-85122564281 12/01/2021
(May SC, Dron JS, Hegele RA, Sahoo D.) J Lipid Res. 2021;62:100045 PMID: 33577783 PMCID: PMC7985710 SCOPUS ID: 2-s2.0-85104445414 02/13/2021
(Schill RL, Knaack DA, Powers HR, Chen Y, Yang M, Schill DJ, Silverstein RL, Sahoo D.) FEBS J. 2020 02;287(4):695-707 PMID: 31386799 PMCID: PMC7002295 SCOPUS ID: 2-s2.0-85070750063 08/07/2019
(Chen Y, Yang M, Huang W, Chen W, Zhao Y, Schulte ML, Volberding P, Gerbec Z, Zimmermann MT, Zeighami A, Demos W, Zhang J, Knaack DA, Smith BC, Cui W, Malarkannan S, Sodhi K, Shapiro JI, Xie Z, Sahoo D, Silverstein RL.) Circ Res. 2019 12 06;125(12):1087-1102 PMID: 31625810 PMCID: PMC6921463 SCOPUS ID: 2-s2.0-85076330129 10/19/2019
(Rodriguez A, Trigatti BL, Mineo C, Knaack D, Wilkins JT, Sahoo D, Asztalos BF, Mora S, Cuchel M, Pownall HJ, Rosales C, Bernatchez P, Ribeiro Martins da Silva A, Getz GS, Barber JL, Shearer GC, Zivkovic AM, Tietge UJF, Sacks FM, Connelly MA, Oda MN, Davidson WS, Sorci-Thomas MG, Vaisar T, Ruotolo G, Vickers KC, Martel C.) Arterioscler Thromb Vasc Biol. 2019 12;39(12):2457-2467 PMID: 31597448 PMCID: PMC6937204 SCOPUS ID: 2-s2.0-85075813183 10/11/2019
(Proudfoot SC, Sahoo D.) Biochem J. 2019 03 22;476(6):951-963 PMID: 30837308 PMCID: PMC6430181 SCOPUS ID: 2-s2.0-85063681808 03/07/2019
(Lange PT, Schorl C, Sahoo D, Tarakanova VL.) mBio. 2018 07 17;9(4) PMID: 30018108 PMCID: PMC6050960 SCOPUS ID: 2-s2.0-85055540133 07/19/2018
(Reneau J, Goldblatt M, Gould J, Kindel T, Kastenmeier A, Higgins R, Rengel LR, Schoyer K, James R, Obi B, Moosreiner A, Nicholson K, Sahoo D, Kidambi S.) PLoS One. 2018;13(6):e0198889 PMID: 29924824 PMCID: PMC6010237 SCOPUS ID: 2-s2.0-85048771061 06/21/2018