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
Research Associate II
- Gabriella Papale, PhD (2008-2012)
- Alexandra Chadwick, PhD (2010-2015)
- Rebecca Schill, PhD (2012-2018)
Na/K-ATPase suppresses LPS-induced pro-inflammatory signaling through Lyn.
(Zhang J, Chang J, Beg MA, Huang W, Zhao Y, Dai W, Wu X, Cui W, Pillai SS, Lakhani HV, Sodhi K, Shapiro JI, Sahoo D, Zheng Z, Silverstein RL, Chen Y.) iScience. 2022 Sep 16;25(9):104963 PMID: 36072548 PMCID: PMC9442361 SCOPUS ID: 2-s2.0-85137074779 09/09/2022
A short amphipathic alpha helix in scavenger receptor BI facilitates bidirectional HDL-cholesterol transport.
(May SC, Sahoo D.) J Biol Chem. 2022 Sep;298(9):102333 PMID: 35926711 PMCID: PMC9436806 SCOPUS ID: 2-s2.0-85136562503 08/05/2022
Regulation of Adipocyte Metabolic Homeostasis by SR-BI and PCPE2.
(Knaack DA, Sorci-Thomas MG, Thomas MJ, Chen Y, Sahoo D.) FASEB J. 2022 May;36 Suppl 1 PMID: 35553852 SCOPUS ID: 2-s2.0-85130030599 05/14/2022
A Tale of Two Scavenger Receptors: Structure-Function Relationships of Purified SR-B1 and CD36.
(Powers HR, Jenjak SE, Volkman BF, Sahoo D.) FASEB J. 2022 May;36 Suppl 1 PMID: 35552332 SCOPUS ID: 2-s2.0-85130046210 05/14/2022
Novel Roles of FFAR4 in Macrophage Foam Cell Formation
(Stuttgen GM, Sahoo D.) FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 1 May 2022;36 PMID: 35553911 SCOPUS ID: 2-s2.0-85130053642 05/01/2022
SR-B1's Next Top Model: Structural Perspectives on the Functions of the HDL Receptor.
(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
(Natarajan R, Moore K, Sahoo D, Nana-Sinkam P, Fowler AAB 3rd, Sime P, Sorci-Thomas M, Aikawa E, ATVB Council, friends, and colleagues.) Arterioscler Thromb Vasc Biol. 2022 Mar;42(3):239-240 PMID: 36808997 SCOPUS ID: 2-s2.0-85148678313 02/23/2023
Pcpe2, a Novel Extracellular Matrix Protein, Regulates Adipocyte SR-BI-Mediated High-Density Lipoprotein Uptake.
(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 Nov;41(11):2708-2725 PMID: 34551590 PMCID: PMC8551036 SCOPUS ID: 2-s2.0-85118592107 09/24/2021
Low-Density Lipoprotein Receptor Suppresses the Endogenous Cholesterol Synthesis Pathway To Oppose Gammaherpesvirus Replication in Primary Macrophages.
(Aurubin CA, Knaack DA, Sahoo D, Tarakanova VL.) J Virol. 2021 Aug 10;95(17):e0064921 PMID: 34105999 PMCID: PMC8354329 SCOPUS ID: 2-s2.0-85112335753 06/10/2021
FFAR4: A New Player in Cardiometabolic Disease?
(Stuttgen GM, Sahoo D.) Endocrinology. 2021 Aug 01;162(8) PMID: 34043793 PMCID: PMC8218936 SCOPUS ID: 2-s2.0-85109115515 05/28/2021
Now in 3D! Novel insights into CD36 structure and function
(May SC, Sahoo D.) Annals of Blood. December 2021;6 SCOPUS ID: 2-s2.0-85122564281 12/01/2021
Human variant of scavenger receptor BI (R174C) exhibits impaired cholesterol transport functions.
(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