The research focus of the Chen Laboratory is to understand the molecular mechanisms of atherosclerosis and vascular inflammation. We investigate the role of toll-like receptors and innate immunity in hypercholesterolemic mouse models of atherosclerosis, as well as the role of these innate immune receptors on Chlamydophila (C.) pneumonia-induced acceleration of atherosclerosis. C. pneumonia-induced acceleration of atherosclerosis was significantly dependent on NLRP3 and caspase-1. The Chen Lab discovered that C. pneumonia-induced extracellular IL-1β triggers a negative feedback loop to inhibit GPR109a and ABCA1 expression and cholesterol efflux leading to accumulation of intracellular cholesterol and foam cell formation. GPR109a and ABCA1 were both upregulated in plaque lesions in NLRP3 −/− mice in both hyperlipidemic and C. pneumonia infection models. Mature IL-1β and cholesterol may compete for access to the ABCA1 transporter to be exported from macrophages. C. pneumonia exploits this metabolic-immune crosstalk, which can be modulated by NLRP3 inhibitors to alleviate atherosclerosis.
The Chen Lab shows that RIP2 deficiency in CD4 + T cells resulted in chronic and severe interleukin-17A-mediated inflammation during C. pneumonia lung infection, increased T helper 17 cell formation in lungs of infected mice and accelerated atherosclerosis. Sex differences in the differential role of NLRP3 inflammasome is also being invested.
The Chen Laboratory is affiliated with the Infectious and Immunologic Diseases Research Center, Department of Biomedical Sciences and the Pediatrics Department.
My focus is on understanding mechanisms of vascular inflammation and sex differences in atherosclerosis. Other areas being investigated are the link between autoimmune diseases, such as systemic lupus erythematosus, and increased risk of cardiovascular disease to discover new and more efficacious treatments for patients with these disorders.
Shuang Chen, MD, PhD
- Pristane Systemic Lupus Erythematosus Mouse Model
- Innate Immunity and Atherosclerosis
- Sex-Specific Effects of the NLRP3 Inflammasome on Atherogenesis in Low-Density Lipoprotein Receptor-Deficient Mice
Meet Our Team
Learn more about the scientists, faculty members, investigators and other healthcare professionals of the Chen Laboratory, whose dedicated efforts lead to groundbreaking discoveries.
Chen S, Shimada K, Crother T, Erbay E, Shah PK, Arditi M.
J Am Coll Cardiol. 2018 Apr 10;71(14):1553-1570.
Tumurkhuu G, Shimada K, Dagvadorj J, Crother TR, Zhang W, Luthringer D, Gottlieb RA, Chen S*, Arditi M* (*co-senior author).
Circ Res. 2016 Jul 6. pii:CIRCRESAHA.116.308362.
Tumurkhuu G, Dagvadorj J, Porritt RA, Crother TR, Shimada K, Tarling EJ, Erbay E, Arditi M, Chen S.
Cell Metab. 2018 Sep 4;28(3):432-448.e4.
Chen S, Markman J, Shimada K, Crother TR, Lane M, Abeles A, Shah PK, Arditi M.
JACC Basic Transl Sci. 2020 Jun;5(6):582-598.
Contact the Chen Lab
8700 Beverly Blvd.
Davis Building, Room D4018
Los Angeles, CA 90048