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Sarah Proudfoot

Sarah Proudfoot_Academic Profile

Sarah Proudfoot

Graduate Student

Locations

  • Biochemistry

Contact Information

Biography

Mentor: Daisy Sahoo, PhD
Year Entered MCW: 2014
Previous Education: BS, Biology; Minor, Chemistry, Alma College

Research Interests

High density lipoproteins (HDL) or “good cholesterol” protect against atherosclerosis by clearing excess circulating cholesterol in two critical steps: (1) HDL extracts cholesterol from peripheral cells. (2) HDL delivers its cholesterol cargo into liver cells for excretion from the body. The movement of cholesterol between cells and HDL is mediated by a receptor known as scavenger receptor BI (or SR-BI). 

SR-BI is a cell surface receptor with a large extracellular domain anchored by two transmembrane domains. My thesis work is focused on identifying and testing the importance of key structural features of SR-BI by designing SR-BI mutants and measuring their function in cells using radiolabeled cholesterol tracers. To date, I have pinpointed several proline residues within SR-BI that are critical for its protein expression and cholesterol transport functions. I have further identified a putative “juxtamembrane” or membrane-interacting alpha-helix in SR-BI that we suspect to form contacts with the plasma membrane via the hydrophobic face of the amphipathic alpha-helix.

My current work aims to clarify the role of SR-BI receptor dimerization in vivo, using a dimerization-null mutant (delta-LZ), wherein the leucine zipper dimerization motif has been substituted with alanine residues. I am using adeno-associated virus to express wild-type or the mutant delta-LZ-SR-BI receptors in SR-BI knockout mice. Macrophages labeled with [3H]-cholesterol will be injected into the mice and [3H]-cholesterol will be measured in the plasma, liver, and feces to test our hypothesis that SR-BI dimerization is required for proper whole-body cholesterol clearance.

Publications

Proline residues in scavenger receptor-BI's C-terminal region support efficient cholesterol transport.
Proudfoot SC, Sahoo D.
Biochem J. 2019 Mar 22;476(6):951-963. doi: 10.1042/BCJ20180831.

Role of Protein Phosphatase 1 and Inhibitor of Protein Phosphatase 1 in Nitric Oxide-Dependent Inhibition of the DNA Damage Response in Pancreatic β-Cells.
Oleson BJ, Naatz A, Proudfoot SC, Yeo CT, Corbett JA.
Diabetes. 2018 May;67(5):898-910. doi: 10.2337/db17-1062. Epub 2018 Feb 14.

NMR Structure of the C-Terminal Transmembrane Domain of the HDL Receptor, SR-BI, and a Functionally Relevant Leucine Zipper Motif.
Chadwick AC, Jensen DR, Hanson PJ, Lange PT, Proudfoot SC, Peterson FC, Volkman BF, Sahoo D.
Structure. 2017 Mar 7;25(3):446-457. doi: 10.1016/j.str.2017.01.001. Epub 2017 Feb 2.

Epac Signaling Is Required for Cocaine-Induced Change in AMPA Receptor Subunit Composition in the Ventral Tegmental Area.
Liu X, Chen Y, Tong J, Reynolds AM, Proudfoot SC, Qi J, Penzes P, Lu Y, Liu QS.
J Neurosci. 2016 Apr 27;36(17):4802-15. doi: 10.1523/JNEUROSCI.3186-15.2016.