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Sahoo Laboratory

Location

Health Research Center

H4930

General Interests

Lipoprotein Metabolism, Scavenger Receptors, Cardiovascular Disease, Diabetes, Obesity

View Daisy Sahoo, PhD Bio
Daisy Sahoo Laboratory

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

Kay Nicholson

kaynicholson

Research Associate II
knichols@mcw.edu

Oversight of all lab activities including laboratory safety, ordering, and training of undergraduate, medical and graduate students.

Darcy Knaack

darcyknaack

Graduate Student (IDP program)
dknaack@mcw.edu

The roles of PCPE2 and SR-BI in mediating cholesterol transport in adipocytes

Sarah Proudfoot

sarahproudfoot

Graduate Student (IDP program)
sproudfoot@mcw.edu

Correlating features of the extracellular domain of SR-BI to its HDL-cholesterol transport functions

Gage Stuttgen

Gage Stuttgen

Graduate Student (IDP program)
gstuttgen@mcw.edu

Understanding how nutrient sensing mechanisms through G protein-coupled receptors influence reverse cholesterol transport and lead to the progression of atherosclerosis and cardiovascular disease.

Hayley Powers

Hayley Powers

Graduate Student (MSTP MD/PhD program)
hpowers@mcw.edu

Elucidating the structure and oligomeric properties of SR-BI, the HDL receptor

Alumni/Former Trainees

  • Gabriella Papale, PhD (2008-2012)
  • Alexandra Chadwick, PhD (2010-2015)
  • Rebecca Schill, PhD (2012-2018)

Recent Publications