Testing Small Molecule Inducers of Trib1 for Effects on LDL Cholesterol

Mentors: Adam Skepner and Marek Nagiec

Heart disease patients frequently take drugs called statins, in order to lower LDL cholesterol levels. In many patients, however, statins have insufficient efficacy and occasionally dose-limiting side effects, such as muscle pain, joint pain, and nausea. Chaewon worked this summer to identify chemical compounds that will lower LDL cholesterol levels in mouse liver cells, by affecting expression of three cholesterol-related genes (Ldlr, Trib1, and Pcsk9).

LDL receptor (LDLR) mediates uptake of LDL cholesterol into cells, so increasing LDLR expression decreases levels of cholesterol in the blood. The recently discovered TRIB1 and PCSK9 genes also affect LDL cholesterol levels. Chaewon worked to evaluate the effects that chemical compounds would have, on the expression of Trib1, Ldlr, and Pcsk9 in mouse liver cells. Chaewon found that the compounds had some similar effects on mouse cells versus human cells, but other effects differed between the two cell types.



Chaewon, a senior at Brookline high school, studied the response of a mouse liver cancer cells to chemical compounds that may help lower LDL cholesterol levels.