The University of Texas Health Science Center at Houston
McGovern Medical School
Institute of Molecular Medicine
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 translocalize 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.
Education & Training
The University of Texas Southwestern Medical Center at Dallas.
University of California, Riverside.
West China University of Medical Sciences.
Targeting Adipose Tissue Remodeling for Treatment of Obesity and Related Diseases, such as Type 2 Diabetes, Cardiovascular Diseases and Cancer.