Sahoo Laboratory
Location
Health Research Center
H4930
General Interests
Lipoprotein Metabolism, Scavenger Receptors, Cardiovascular Disease, Diabetes, Obesity
View Daisy Sahoo, PhD Bio
Research Areas
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?
Techniques
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
Current Members
Scenes from the Sahoo Laboratory
Alumni/Former Trainees
- Gabriella Papale, PhD (2008-2012)
- Alexandra Chadwick, PhD (2010-2015)
- Rebecca Schill, PhD (2012-2018)
- Darcy Knaack
- Hayley Powers
Recent Publications
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(Bobek JM, Stuttgen GM, Sahoo D.) Front Cardiovasc Med. 2024;11:1448607 PMID: 39328237 PMCID: PMC11424405 09/27/2024
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(Bobek JM, Stuttgen GM, Sahoo D.) Frontiers in Cardiovascular Medicine. 2024;11 SCOPUS ID: 2-s2.0-85204912708 01/01/2024
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(Powers HR, Jenjak SE, Volkman BF, Sahoo D.) J Biol Chem. 2023 Oct;299(10):105187 PMID: 37625590 PMCID: PMC10509710 SCOPUS ID: 2-s2.0-85171377774 08/26/2023
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(Dai W, Zhang H, Lund H, Zhang Z, Castleberry M, Rodriguez M, Kuriakose G, Gupta S, Lewandowska M, Powers HR, Valmiki S, Zhu J, Shapiro AD, Hussain MM, López JA, Sorci-Thomas MG, Silverstein RL, Ginsberg HN, Sahoo D, Tabas I, Zheng Z.) Science. 2023 Sep;381(6661):eadh5207 PMID: 37651538 PMCID: PMC10697821 SCOPUS ID: 2-s2.0-85169348601 08/31/2023
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(Knaack DA, Chang J, Thomas MJ, Sorci-Thomas MG, Chen Y, Sahoo D.) bioRxiv. 2023 Aug 22 PMID: 37662321 PMCID: PMC10473602 09/04/2023
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(Pillai SS, Pereira DG, Zhang J, Huang W, Beg MA, Knaack DA, de Souza Goncalves B, Sahoo D, Silverstein RL, Shapiro JI, Sodhi K, Chen Y.) Front Cardiovasc Med. 2023;10:1046495 PMID: 37180782 PMCID: PMC10174328 SCOPUS ID: 2-s2.0-85159873988 05/14/2023
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(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
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(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
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(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
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(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
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(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
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(May SC, Sahoo D.) Annals of Blood. December 2021;6 SCOPUS ID: 2-s2.0-85122564281 12/01/2021