Identifying Small Molecule Modulators of Lipoprotein Regulation

Mentors: Joseph Negri, Melissa Bennion, Patrick Faloon

The human body requires cholesterol for many functions, at low levels. Cholesterol travels through the blood in LDL (or “bad cholesterol”) and HDL (or “good cholesterol”) complexes. The accumulation of LDL particles in the blood causes LDLs to deposit the cholesterol on arterial walls, leading to atherosclerosis.

Chemical compounds that lower LDL levels could drastically lower the incidence of heart disease. Therefore Garrett screened a collection of 11, 570 chemical compounds, for those that change the regulation of two genes – Sortilin 1 and Tribbles 1 – which have been reported to reduce LDL levels. Using the qPCR method, Garrett identified 7 potential inducers of Sortilin transcription, and 61 potential small molecule inhibitors of Tribbles transcription.

Chemical compounds that inhibit the activity of SR-B1 could provide new routes to treating various diseases and conditions, because uptake of HDL cholesterol into cells occurs when HDL interacts with the cell membrane protein SR-B1. Therefore Garrett tested several molecules for their abilities to inhibit HDL cholesterol uptake via SR-B1, and found several promising molecules.



Garrett, a senior at Wellesley High School, discovered chemical compounds that affect the levels of LDL and HDL (“bad” & “good” cholesterol, respectively) uptake into cells, from the blood.