Shengyi Iris Sun

Education

• Cornell University, PhD, 2015

Research Focus

The Sun laboratory has two major focuses on protein degradation in the endoplasmic reticulum (ER) and inflammation. ER-associated degradation (ERAD) is a fundamental quality-control process that recognizes and targets ER proteins for cytosolic proteasomal degradation, central to human health and diseases. In fact, defects in protein maturation and turnover in the ER underlie the pathogenesis of many human diseases and moreover, many viruses co-opt ERAD apparatus to establish infection and escape immune surveillance. However, little is known about the physiological role of ERAD. Recent studies have established that low-grade inflammation may play a causal role in obesity-associated insulin resistance, type 2 diabetes, and other complications. However, how the inflammation and innate immunity crosstalk with metabolic processes to regulate metabolism remains poorly understood. We are interested in the role of Toll-like receptor signaling pathways in regulating pancreatic β cell proliferation. In the Sun laboratory, we use physiological, immunological, molecular and cellular approaches to dissect the molecular processes of inflammation and ER protein degradation in the context of metabolic diseases, thereby producing exciting new insights into disease pathogenesis and treatment.

Research Areas

• Metabolism
• Diabetes
• Protein Structure and Function
• Cell Signaling

Recent Publications

Xu, L., Liu, X., Peng, F., Zhang, W., Zheng, L., Ding, Y., Gu, T., Lv, K., Wang, J., Ortinau, L.C., Hu, T., Shi, C., Shi, G., Shang, G., Sun, S., Iwawaki, T., Ji, Y., Li, W., Rosen, J.M., Zhang, X.H.F., Park, D., Adoro, S., Catic, A., Wei, T., Qi, L., Nakada, D., and Chen, X. Protein quality control through ERAD maintains hematopoietic stem cell identity and niche interactions. Nat Cell Biol. 2020 Sep 21. PubMed PMID: 32958856.

Sun S, Kelekar S, Kliewer S, Mangelsdorf D. The orphan nuclear receptor SHP regulates ER stress response by inhibiting XBP1s degradation. Genes & development. 2019 Aug 1;33(15-16):1083-1094. PubMed PMID: 31296559; PubMed Central PMCID: PMC6672048.

Ji Y*, Sun S*, Shrestha N, Darragh LB, Shirakawa J, Xing Y, He Y, Carboneau BA, Kim H, An D, Ma M, Oberholzer J, Soleimanpour SA, Gannon M, Liu C, Naji A, Kulkarni RN, Wang Y, Kersten S, Qi L. Toll-like receptors TLR2 and TLR4 block the replication of pancreatic β cells in diet-induced obesity. Nat Immunol. 2019 Jun;20(6):677-686. PubMed PMID: 31110312; PubMed Central PMCID: PMC6531334. (*, contributed equally)

Sun S#, Lourie R, Cohen SB, Ji Y, Goodrich JK, Poole AC, Ley RE, Denkers EY, McGuckin MA, Long Q, Duhamel GE, Simpson KW, Qi L#. Epithelial Sel1L is required for the maintenance of intestinal homeostasis. Mol Biol Cell. 2016 Feb 1;27(3):483-90. PubMed PMID: 26631554; PubMed Central PMCID: PMC4751599. (#, co-corresponding authors)

Sun S*, Shi G*, Sha H, Ji Y, Han X, Shu X, Ma H, Inoue T, Gao B, Kim H, Bu P, Guber RD, Shen X, Lee AH, Iwawaki T, Paton AW, Paton JC, Fang D, Tsai B, Yates JR 3rd, Wu H, Kersten S, Long Q, Duhamel GE, Simpson KW, Qi L. IRE1α is an endogenous substrate of endoplasmic-reticulum-associated degradation. Nat Cell Biol. 2015 Dec;17(12):1546-55. PubMed PMID: 26551274; PubMed Central PMCID: PMC4670240. (*, contributed equally)

Ji Y*, Sun S*, Goodrich JK, Kim H, Poole AC, Duhamel GE, Ley RE, Qi L. Diet-induced alterations in gut microflora contribute to lethal pulmonary damage in TLR2/TLR4-deficient mice. Cell Rep. 2014 Jul 10;8(1):137-49. PubMed PMID: 24953658; PubMed Central PMCID: PMC4103790. (*, contributed equally)

Sun S*, Shi G*, Han X, Francisco AB, Ji Y, Mendonça N, Liu X, Locasale JW, Simpson KW, Duhamel GE, Kersten S, Yates JR 3rd, Long Q, Qi L. Sel1L is indispensable for mammalian endoplasmic reticulum-associated degradation, endoplasmic reticulum homeostasis, and survival. Proc Natl Acad Sci U S A. 2014 Feb 4;111(5):E582-91. PubMed PMID: 24453213; PubMed Central PMCID: PMC3918815. (*, contributed equally)

Sun S, Xia S, Ji Y, Kersten S, Qi L. The ATP-P2X7 signaling axis is dispensable for obesity-associated inflammasome activation in adipose tissue. Diabetes. 2012 Jun;61(6):1471-8. PubMed PMID: 22415881; PubMed Central PMCID: PMC3357307.

Sun S, Ji Y, Kersten S, Qi L. Mechanisms of inflammatory responses in obese adipose tissue. Annu Rev Nutr. 2012 Aug 21;32:261-86. PubMed PMID: 22404118; PubMed Central PMCID: PMC4041712.