Daisy Sahoo, PhD
Vice Chair for Research, Division of Endocrinology and Molecular Medicine; Professor, Medicine (Endocrinology); Secondary Faculty in Biochemistry and Pharmacology and Toxicology
- Health Research Center
The role of scavenger receptors in cardiovascular disease and related 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. This process termed “selective uptake” requires two steps: (i) HDL must bind to the extracellular domain of SR-BI and (ii) lipid alone is transferred from HDL to the plasma membrane, without holoparticle uptake. 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.
To accomplish these goals, our laboratory is currently studying the following:
- The molecular architecture of the extracellular domain of SR-BI (using novel fluorescence strategies and other biochemical techniques);
- The oligomeric properties of SR-BI;
- The mechanisms of HDL-CE delivery and hydrolysis at the plasma membrane
- The impact of modified HDL on selective uptake of HDL lipids.
(Schill RL, Knaack DA, Powers HR, Chen Y, Yang M, Schill DJ, Silverstein RL, Sahoo D.) FEBS J. 2020 Feb;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 Dec 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 Dec;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
(Dong L, Yuan Y, Opansky C, Chen Y, Aguilera-Barrantes I, Wu S, Yuan R, Cao Q, Cheng YC, Sahoo D, Silverstein RL, Ren B.) Oncotarget. 2017 Apr 04;8(14):22550-22562 PMID: 28186980 PMCID: PMC5410244 SCOPUS ID: 2-s2.0-85016933174 02/12/2017
(Chadwick AC, Jensen DR, Hanson PJ, Lange PT, Proudfoot SC, Peterson FC, Volkman BF, Sahoo D.) Structure. 2017 03 07;25(3):446-457 PMID: 28162952 PMCID: PMC5575897 SCOPUS ID: 2-s2.0-85011284406 02/07/2017
(Afolayan AJ, Alexander M, Holme RL, Michalkiewicz T, Rana U, Teng RJ, Zemanovic S, Sahoo D, Pritchard KA Jr, Konduri GG.) J Biol Chem. 2017 02 10;292(6):2369-2378 PMID: 28028182 PMCID: PMC5313107 SCOPUS ID: 2-s2.0-85012108909 12/29/2016
(Holme RL, Miller JJ, Nicholson K, Sahoo D.) Biochemistry. 2016 Jan 12;55(1):103-13 PMID: 26652912 PMCID: PMC5428993 SCOPUS ID: 2-s2.0-84954457161 12/15/2015
(Korytowski W, Wawak K, Pabisz P, Schmitt JC, Chadwick AC, Sahoo D, Girotti AW.) Arterioscler Thromb Vasc Biol. 2015 Oct;35(10):2104-13 PMID: 26315403 PMCID: PMC4601804 SCOPUS ID: 2-s2.0-84942259316 09/01/2015
(Chen Y, Kennedy DJ, Ramakrishnan DP, Yang M, Huang W, Li Z, Xie Z, Chadwick AC, Sahoo D, Silverstein RL.) Sci Signal. 2015 Sep 08;8(393):ra91 PMID: 26350901 PMCID: PMC4852751 SCOPUS ID: 2-s2.0-84941034207 09/10/2015