Sissel Lund-Katz, PhD
- Department: Pediatrics
- Division: GI/Nutrition
- Address:
34th & Civic Center Blvd.
Abramson, Room 1102E
Philadelphia, PA 19104 - Phone: (215)590-0588
- Email: katzs@email.chop.edu
Research Summary:
My research interests are directed at relating the structure of serum lipoproteins - complexes of fats and proteins present in the blood - to their function in lipid and cholesterol transport and to the development of atherosclerosis. Specifically, I focus on the role of one of the structural proteins of lipoproteins, apolipoprotein (apo) E, which is involved in lipoprotein metabolism, prevention of plaque formation in the arteries and mediation of neuronal repairs, remodeling and protection.
Apo E prevents plaque buildup through its interaction with lipids and cell surface molecules, such as members of the low density lipoprotein receptor (LDLR) family and glycosaminoglycans (GAG). However, the structural basis for these interactions and the role of the three major isoforms of apo E (apo E2, apo E3 and apo E4) are not fully understood. Apo E2 leads to type III hyper-lipoproteinemia and apo E4 leads to both high cholesterol levels and Alzheimer's disease.
I am using a range of engineered apo E molecules expressed in E. coli to understand the molecular features that control the binding of apo E and its common isoforms to lipid and lipoprotein particles of different sizes. Using both in vitro and in vivo approaches, I am characterizing the interactions of apo E with lipoprotein particles. I am also exploring the lipid efflux and the nascent apo E/HDL particle formation that occurs when apo E is a ligand for the ATP binding cassette transporter A1 in neuronal cells. To understand how the receptor binding domain of apo E modulates its binding to different sulfated proteoglycans and GAG as compared to members of the LDLR family, I am determining the affinities and kinetics of interaction using surface plasmon resonance and cell-based assays.
My long-term research goal is to design molecules that mimic the function of apo E and to establish ways to control the abnormal behavior of certain isoforms of apo E.
