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Cardiovascular Center

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Daisy Sahoo Lab

Daisy Sahoo

Daisy Sahoo, PhD
Professor, Medicine (Endocrinology)
Vice Chair for Research
dsahoo@mcw.edu

Dr. Sahoo’s research interests

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:

  1. The molecular architecture of the extracellular domain of SR-BI (using novel fluorescence strategies and other biochemical techniques);
  2. The oligomeric properties of SR-BI;
  3. The mechanisms of HDL-CE delivery and hydrolysis at the plasma membrane
  4. The impact of modified HDL on selective uptake of HDL lipids

Kay Nicholson

Kay Nicholson
Research Associate II
knichols@mcw.edu

 

Darcy Knaack

Darcy Knaack
Research Assistant
dknaack@mcw.edu

Sarah Proudfoot

Sarah Proudfoot
Research Assistant
sproudfoot@mcw.edu

 

Hayley Powers
Research Assistant

Alumni/Former Trainees

  • Gabriella Kartz (nee Papale)
  • Alexandra Chadwick, PhD
  • Rebecca Schill

Recent Publications