Year Entered MCW: 2014
Previous Education: BS, Biology; Minor, Chemistry, Alma College
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.
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.