Biography

Dr. Sun received his medical degree from West China University of Medical Sciences, MPH from Peking University, and Ph.D degree from University of California, Riverside. He finished his postdoctoral training in Dr. Philipp Scherer’s laboratory at UT Southwestern Medical Center where he had obtained a remarkable set of observations about adipose tissue remodeling and obesity. He had published the paradigm-shifting findings in high-impact journals such as PNAS, JCI, and Cell Metabolism. In 2015, Dr. Sun was recruited to the Institute of Molecular Medicine.

Areas of Interest

Research Interests

Our lab is focused on uncovering and understanding the factors that lead to alterations in adipose tissue during obesity development. Our primary goal is to determine how these factors are connected to health issues like obesity, diabetes, cardiovascular diseases, and the initiation and progression of cancer.

We have found that diet-induced obesity generates a hypoxic (low oxygen) environment in adipose tissue, which triggers inflammation and fibrosis. This unhealthy state of adipose tissue is a major contributor to systemic insulin resistance and metabolic dysfunctions. Interestingly, we discovered that angiogenesis, stimulated by VEGF-A, alleviates these negative effects by  forming new functional blood vessels and enhancing sympathetic innervation in both white and brown adipose tissues. Our studies also indicate that the enzyme MT1-MMP, under hypoxic conditions, promotes the healthy expansion of adipose tissue through synergistic action with VEGF-A to enhance blood flow, thus mitigating adverse effects.

In our most recent research, we delved into the dynamic regulation of proteins associated with lipid droplets during the progression of obesity and cancer.  By utilizing mass spectrometry, we identified several novel proteins that translocate to lipid droplets or to the interfaces between the endoplasmic reticulum (ER), mitochondria, and lipid droplets in response to different stimuli, including Drp1 and Ces1d. Specifically, Ces1d is recruited to lipid droplets in response to β-adrenergic signals and nutritional stresses, where it plays a role in lipid breakdown through lipolysis. A meta-analysis of clinical data has shown a significant increase in Ces1d levels in certain types of cancer, closely associated with higher mortality rates, highlighting Ces1d as a promising target for cancer therapy. We are currently utilizing cutting-edge methodologies to further dissect the functions of these newly identified factors and their potential implications for metabolic health and cancer therapy.

Research Projects

  1. Investigating the pathological changes in adipose tissue induced by hypoxia.
  2. Studying the impact of angiogenesis and sympathetic innervation on adipose tissue and its influence on energy expenditure.
  3. Examining the potential for reversing adipose tissue fibrosis through novel anti-fibrotic treatments.
  4. Exploring the interplay between lipid droplets, mitochondria, and the ER, and their significance in metabolic diseases and cancer progression.

Publications

Visit the PubMed profile page

Li G*, Li X*, Mahmud I, Ysaguirre J, Fekry B, Wang S, Wei B, Eckel-Mahan K, Lorenzi PL, Lehner R, Sun K. Interfering with lipid metabolism through targeting CES1 sensitizes hepatocellular carcinoma for chemotherapy. 2023, JCI Insight 2023 Jan 24;8(2):e163624. PMID: 36472914

Li G, Li X, Yang L, Wang S, Dai Y, Fekry B, Veillon L, Tan L, Berdeaux R, Eckel-Mahan K, Lorenzi PL, Zhao Z, Lehner R, Sun K. Adipose tissue-specific ablation of Ces1d causes metabolic dysregulation in mice. Life Sci Alliance. 2022 Apr 22;5(8):e202101209. PMC9034061

Cox AR, Masschelin PM, Saha PK, Felix JB, Sharp R, Lian Z, Xia Y, Chernis N, Bader DA, Kim KH, Li X, Yoshino J, Li X, Li G, Sun Z, Wu H, Coarfa C, Moore DD, Klein S, Sun K, Hartig SM. The rheumatoid arthritis drug auranofin lowers leptin levels and exerts antidiabetic effects in obese mice. Cell Metab. 2022 Oct 10:S1550-4131(22)00409-0. PMID: 36243005

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. Novel role of dynamin-related-protein 1 in dynamics of ER-lipid droplets in adipose tissue.  FASEB J. 2020 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.  The critical role of MMP14 in adipose tissue remodeling during obesity. Mol Cell Biol. 2020 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. Obesity-Induced Regulator of Calcineurin 1 Overexpression Leads to β-Cell Failure Through Mitophagy Pathway Inhibition. Antioxid Redox Signal. 2020 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. Dysregulation of Amyloid Precursor Protein Impairs Adipose Tissue Mitochondrial Function and Promotes Obesity. Nat Metab. 2019 Dec;1(12):1243-1257.  PMCID: PMC6980705

Yang L, Li X, Tang H, Gao Z, Zhang K, Sun K.  A Unique Role of Carboxylesterase 3 (Ces3) in β-Adrenergic Signaling-Stimulated Thermogenesis. Diabetes. 2019 Jun; 68(6):1178-1196.  PMCID: PMC6610024

Li X, Mao Z, Yang L, Sun K. Co-staining Blood Vessels and Nerve Fibers in Adipose Tissue. J Vis Exp. 2019 Feb 13 (144):10.3791/59266.  PMCID: PMC6989151

Zhao Y, Gu X, Zhang N, Kolonin MG, An Z, Sun K. Divergent functions of endotrophin on different cell populations in adipose tissue. Am J Physiol Endocrinol Metab. 2016 Dec 1;311(6):E952-E963.  PMCID: PMC6189636

Li X, Sun K.  Regulation of Lipolysis in Adipose Tissue and Clinical Significance. Adv Exp Med Biol. 2018;1090:199-210.

Sun K, Gao Z, Kolonin MG. Transient inflammatory signaling promotes beige adipogenesis. Sci Signal. 2018 Apr 24;11(527):eaat3192.

Zhao Y, Li X, Yang L, Eckel-Mahan K, Tong Q, Gu X, Kolonin MG, Sun K. Transient Overexpression of Vascular Endothelial Growth Factor A in Adipose Tissue Promotes Energy Expenditure via Activation of the Sympathetic Nervous System. Mol Cell Biol. 2018 Oct 29;38(22):e00242-18.  PMCID: PMC6206456