PhD, Biochemistry, University of Alberta, 2001
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.
(Lange PT, Schorl C, Sahoo D, Tarakanova VL.) MBio. 2018 Jul 17;9(4).
(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.
(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.
(Chadwick AC, Jensen DR, Hanson PJ, Lange PT, Proudfoot SC, Peterson FC, Volkman BF, Sahoo D.) Structure. 2017 03 07;25(3):446-457.
(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.
(Holme RL, Miller JJ, Nicholson K, Sahoo D.) Biochemistry. 2016 Jan 12;55(1):103-13.
(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.
(Korytowski W, Wawak K, Pabisz P, Schmitt JC, Chadwick AC, Sahoo D, Girotti AW.) Arterioscler Thromb Vasc Biol. 2015 Oct;35(10):2104-13.
Procollagen C-endopeptidase Enhancer Protein 2 (PCPE2) Reduces Atherosclerosis in Mice by Enhancing Scavenger Receptor Class B1 (SR-BI)-mediated High-density Lipoprotein (HDL)-Cholesteryl Ester Uptake.
(Pollard RD, Blesso CN, Zabalawi M, Fulp B, Gerelus M, Zhu X, Lyons EW, Nuradin N, Francone OL, Li XA, Sahoo D, Thomas MJ, Sorci-Thomas MG.) J Biol Chem. 2015 Jun 19;290(25):15496-511.
(Chadwick AC, Holme RL, Chen Y, Thomas MJ, Sorci-Thomas MG, Silverstein RL, Pritchard KA Jr, Sahoo D.) PLoS One. 2015;10(4):e0123138.
(Kropp EM, Oleson BJ, Broniowska KA, Bhattacharya S, Chadwick AC, Diers AR, Hu Q, Sahoo D, Hogg N, Boheler KR, Corbett JA, Gundry RL.) Stem Cells Transl Med. 2015 May;4(5):483-93.
(Chan CK, Seo EY, Chen JY, Lo D, McArdle A, Sinha R, Tevlin R, Seita J, Vincent-Tompkins J, Wearda T, Lu WJ, Senarath-Yapa K, Chung MT, Marecic O, Tran M, Yan KS, Upton R, Walmsley GG, Lee AS, Sahoo D, Kuo CJ, Weissman IL, Longaker MT.) Cell. 2015 Jan 15;160(1-2):285-98.