Kai Sun, M.B., Ph.D.
- Associate Professor, The Brown Foundation Institute of Molecular Medicine, Center for Metabolic & Degenerative Diseases
- Postdoctoral Fellow
- The University of Texas Southwestern Medical Center at Dallas, 2011
- University of California, Riverside, 2005
- West China University of Medical Sciences, 1995
Targeting Adipose Tissue Remodeling for Treatment of Obesity and Related Diseases, such as Type 2 Diabetes, Cardiovascular Diseases and Cancer.
My laboratory investigates and discovers novel factors that regulate the dynamics of adipose tissue remodeling during obesity development. The long-term goal of our research is to address the clinical significance of these factors in human obesity, diabetes, cardiovascular diseases, and cancer growth.
In the past years, we have revealed that high fat diet-induced obesity shapes a hypoxic microenvironment that initiates the local fibrosis and inflammation in adipose tissue. The unhealthy adipose tissue further leads to systemic insulin resistance and cardiovascular dysregulation. Intriguingly, we found that VEGF-A-induced angiogenesis ameliorates the pathological changes by suppressing the local hypoxia and stimulating sympathetic innervation in both white and brown adipose tissue. Our study further reveals that the hypoxia-induced MT1-MMP facilitates the healthy expansion of adipose tissue by stimulating angiogenesis in combination with VEGF-A and leptin, thus relieving the pathological conditions. Furthermore, MT1-MMP cleaves collagenous proteins to increase the ECM flexibility in adipose tissue.
Most recently, we analyzed the dynamics of lipid droplet-associated proteins during adipose tissue remodeling by Mass Spectrometry. We have successfully identified several novel proteins that trans-localize onto lipid droplets and the interface of endoplasmic reticulum (ER)-lipid droplets in response to different stimuli. Particularly, one of the identified proteins named Carboxyl Esterase 1 (CES1) targets lipid droplets upon β-adrenergic-stimulation where it exerts the lipolytic function on the lipids. Meta-analysis of clinical data reveals that CES1 levels are significantly increased during the development of a certain types of cancer and are tightly correlated with the death rates, suggesting that CES1 might be a novel target to treat the cancer. We are now applying state-of-the-art tools and techniques to elucidate the mechanisms governing the functions of the novel factors and investigating their potential implication in metabolic health and cancer therapy.
- Hypoxia induced pathological changes in adipose tissue.
- Sympathetic innervation in adipose tissue and energy expenditure.
- Reversibility of adipose tissue fibrosis by novel anti-fibrotic therapies.
- Dynamics of lipid droplets, metabolic regulation and tumor development.
- Liu Z, Xiong J, Gao S, Zhu MX, Sun K, Li M, Zhang G, Li YP. (2022). Ameliorating cancer cachexia by inhibiting cancer cell release of Hsp70 and Hsp90 with omeprazole. J Cachexia Sarcopenia Muscle. Feb;13(1):636-647. PMID: 34729960
- Ribas-Latre A, Santos RB, Fekry B, Tamim YM, Shivshankar S, Mohamed AMT, Baumgartner C, Kwok C, Gebhardt C, Rivera A, Gao Z, Sun K, Heiker JT, Snyder BE, Kolonin MG, Eckel-Mahan KL. (2021). Cellular and physiological circadian mechanisms drive diurnal cell proliferation and expansion of white adipose tissue. Nat Commun. Jun 9;12(1):3482. PMID: 34108488
- Lee JH, Fang C, Li X, Wu CS, Noh JY, Ye X, Chapkin RS, Sun K, Sun Y. (2021). GHS-R suppression in adipose tissues protects against obesity and insulin resistance by regulating adipose angiogenesis and fibrosis. Int J Obes (Lond). Jul;45(7):1565-1575. PMID: 33903722
- Li X, Yang L, Mao Z, Pan X, Zhao Y, Gu X, Eckel-Mahan K, Zuo Z, Tong Q, Hartig SM, Cheng X, Du G, Moore DD, Bellen HJ, Sesaki H, Sun K. (2020). Novel role of dynamin-related-protein 1 in dynamics of ER-lipid droplets in adipose tissue. FASEB J. Jun; 34(6):8265-8282. PMCID: PMC7336545
- Li X, Zhao Y, Chen C, Yang L, Lee HH, Wang Z, Zhang N, Kolonin MG, An Z, Ge X, Scherer PE, Sun K. (2020). The critical role of MMP14 in adipose tissue remodeling during obesity. Mol Cell Biol. Mar; 40(8): e00564-19. PMCID: PMC7108820
- Li X, Chan LWC, Li X, Liu C, Yang G, Gao J, Dai M, Wang Y, Xie Z, Liu J, Zhou F, Zheng T, Feng D, Guo S, Li H, Sun K, Yang S. (2020). Obesity-Induced Regulator of Calcineurin 1 Overexpression Leads to β-Cell Failure Through Mitophagy Pathway Inhibition. Antioxid Redox Signal. Mar 1;32(7):413-428.
- An YA, Crewe C, Asterholm IW, Sun K, Chen S, Zhang F, Shao M, Funcke JB, Zhang Z, Straub L, Klein S, Kusminski CM, Scherer PE. (2019). Dysregulation of Amyloid Precursor Protein Impairs Adipose Tissue Mitochondrial Function and Promotes Obesity. Nat Metab. Dec;1(12):1243-1257. PMCID: PMC6980705
- Yang L, Li X, Tang H, Gao Z, Zhang K, Sun K. (2019). A Unique Role of Carboxylesterase 3 (Ces3) in β-Adrenergic Signaling-Stimulated Thermogenesis. Diabetes. Jun; 68(6):1178-1196. PMCID: PMC6610024
- Li X, Mao Z, Yang L, Sun K. (2019). Co-staining Blood Vessels and Nerve Fibers in Adipose Tissue. J Vis Exp. Feb 13 (144):10.3791/59266. PMCID: PMC6989151
- Li X, Sun K. (2018). Regulation of Lipolysis in Adipose Tissue and Clinical Significance. Adv Exp Med Biol., 1090:199-210.
- Sun K, Gao Z, Kolonin MG. ( 2018). Transient inflammatory signaling promotes beige adipogenesis. Sci Signal. Apr 24;11(527):eaat3192.
- Zhao Y, Li X, Yang L, Eckel-Mahan K, Tong Q, Gu X, Kolonin MG, Sun K. (2018). Transient Overexpression of Vascular Endothelial Growth Factor A in Adipose Tissue Promotes Energy Expenditure via Activation of the Sympathetic Nervous System. Mol Cell Biol. Oct 29;38(22):e00242-18. PMCID: PMC6206456.
- Zhao Y, Gu X, Zhang N, Kolonin MG, An Z, Sun K. (2016). Divergent functions of endotrophin on different cell populations in adipose tissue. Am J Physiol Endocrinol Metab. Dec 1;311(6):E952-E963. PMCID: PMC6189636
- Sun K, Park J, Gupta O, Holland WL, Auerbach PL, Zhang N, Marangoni RG, Nicoloro SM, Czech MP, Varga J, Ploug T, An ZQ and Scherer PE.(2014). Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction. Nature Commun. 5:3485.
- Sun K, Tordjman J, Clément K, and Scherer PE . (2013). Fibrosis and adipose tissue dysfunction. Cell Metab. 18(4):470-7.
- He C, Wei Y*, Sun K*, Li B*, Zou Z, Liu Y, Kinch LN, Khan S, Xavier RJ, Grishin NV, Xiao G, Eskelinen EL, Scherer PE, Whistler JL, and Levine B. (2013). Beclin 2 functions in autophagy, degradation of G protein-coupled receptors, and metabolism. (* contributed equally). Cell. 154(5):1085-99.
- Sun K, Wernstedt Asterholm I, Kusminski CM, Bueno AC, Wang ZV, Pollard JW, Brekken RA, Scherer PE. (2012). Dichotomous effects of VEGF-A on adipose tissue dysfunction. Proc Natl Acad Sci U S A. 109(15):5874-9.
- He C, Bassik MC, Moresi V, Sun K, Wei Y, Zou Z, An Z, Loh J, Fisher J, Sun Q, Korsmeyer S, Packer M, May HI, Hill JA, Virgin HW, Gilpin C, Xiao G, Bassel-Duby R, Scherer PE, and Levine B. (2012). Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis. Nature. 481(7382):511-5.
- Sun K, Kusminski CM, Scherer PE. (2011). Adipose tissue remodeling and obesity. J Clin Invest. 121 (6): 2094-101.
Complete List of Published Work in My Bibliography: