Kai Sun
Associate Professor
The University of Texas Health Science Center at Houston
McGovern Medical School
Institute of Molecular Medicine
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.
Education & Training
Postdoctoral Fellow
The University of Texas Southwestern Medical Center at Dallas.
Ph.D.
University of California, Riverside.
MD
West China University of Medical Sciences.
Research Info
Targeting Adipose Tissue Remodeling for Treatment of Obesity and Related Diseases, such as Type 2 Diabetes, Cardiovascular Diseases and Cancer.