Dr. Kai Sun, MD, PhD

Dr. Kai Sun, MD, PhD

Associate Professor, IMM-Center for Metabolic & Degenerative Diseases

Email Address: Kai.Sun@uth.tmc.edu
Phone Number: 713-500-3190
Room Number: SRB 437A

Narrative

         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.

         Research interests

         Dr. Sun’s laboratory discovers and investigates novel factors that regulate the dynamics of adipose tissue remodeling during obesity and cancer development. The long-term goal is to address the clinical significance of these factors in human obesity, diabetes, cardiovascular disease and cancer.

         In the past years, his laboratory has reported that high fat diet-induced obesity shapes a hypoxic microenvironment that initiates the local fibrosis and inflammation in adipose tissue. The unhealthy adipose tissue eventually leads to systemic insulin resistance and cardiovascular dysregulation. Furthermore, obese adipose tissue further promotes the growth of a certain types of cancer. Intriguingly, he 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. His study further reveals that the hypoxia-induced MT1-MMP facilitates the healthy expansion of adipose tissue by stimulating angiogenesis in combination with VEGF-A, thus relieving the pathological conditions during early stage of obesity; On the other hand, MT1-MMP mediates abnormal   extracellular matrix (ECM) remodeling which leads to local fibrosis in the established obese adipose tissue.

        Most recently, Dr. Sun’s laboratory analyzed the dynamics of lipid droplet-associated proteins during adipose tissue remodeling by Mass Spectrometry. He has successfully identified several novel proteins that translocate onto lipid droplets and/or the interface of endoplasmic reticulum (ER)-lipid droplets in response to different cellular stimuli. Particularly, he discovered that one of the identified proteins named Carboxyl Esterase 1d (Ces1d) targets lipid droplets upon β-adrenergic-stimulation where it exerts the lipolytic function on the lipids. He also discovered that another factor called Dynamin-Related Protein 1 (DRP1) translocates onto ER where it promotes the fission of the nascent lipid droplets from the ER in response to lipid stress. His laboratory continues to apply  state-of-the-art tools and techniques to decipher the mechanisms governing the functions of these novel factors and uncover their potential clinical implications to treat obesity-related metabolic diseases and cancer.

Research Projects

  1. Hypoxia stimulated fibrosis and local inflammation in adipose tissue.
  2. Sympathetic innervation in adipose tissue and energy expenditure).
  3. Reversibility of adipose tissue fibrosis by novel anti-fibrotic therapies.
  4. Regulation of the dynamics of lipid droplets and cancer development.

Recent Publications

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