Tong Wu

MSTP in PhD Training

Program: Immunology

Current advisor: Marco Colonna, MD

Undergraduate university: Duke University, 2021

Enrollment year: 2021

Research summary
Origins and trafficking of high-density lipoprotein subfractions in circulation

This past summer I worked in the lab of Dr. Gwendalyn Randolph, where I investigated the origins of high-density lipoprotein (HDL) subfractions. The majority of the body’s HDL is synthesized from the liver, but a significant portion is also derived from the epithelium of the small intestines. HDL can be generally classified into two subfractions: the less dense, more cholesterol-rich HDL2 and the denser, less cholesterol-rich HDL3. The Randolph lab recently demonstrated that HDL3 can neutralize LPS that disseminates from the small intestines directly into the portal vein. My rotation project aimed to determine whether HDL2 and HDL3 have distinct origins; in other words, does the liver and small intestines predominantly synthesize one fraction or the other. Using mice deficient in either liver-derived HDL (ABCA1-albumin-cre) or intestine-derived HDL (ABCA1-villin-cre) and biochemical approaches, I found that in the portal veinous circulation, which drains directly from the small intestines, HDL3 was reduced in ABCA1-villin-cre mice, but not in ABCA1-albumin-cre mice, while HDL2 fractions remained unchanged. However, in the systemic circulation, both HDL2 and HDL3 were greatly reduced in ABCA1-albumin-cre mice but remain unchanged in ABCA1-villin-cre mice. Future directions include implementing an in-vivo HDL photo-tagging mouse model to track the trafficking of the two HDL subfractions and investigating the implications of these findings in the context of inflammatory bowel disease.

Graduate publications