Our lab is interested in the regulation of energy and nutritional metabolism via three aspects, identifying essential regulatory factors in systemic metabolism, understanding how gut microbiota regulate host metabolism and developing new drugs for treatment of metabolic diseases. We utilize genetic mouse models, cell culture, various omics techniques and self-developed bioinformatics tools to understand the molecular mechanism key factors during disease development and progression and develop therapeutic strategies for pre-clinical trial of several metabolic diseases such obesity and type 2 diabetes.
1. Molecular Regulation of Thermogenic Adipocyte development
Thermogenic adipocytes such as brown and beige adipocyte are new druggable target for metabolic diseases such as obesity, and type 2 diabetes via burning systemic lipid or glucose. A plenty of works have been done to identify factors involved in stimulating beigeing of white adipocyte or activating thermogenesis of brown adipocyte. However, most of these factors relaying external stimuli. We are keen to identify adipocyte-internal regulatory factors or other metabolic organ-derived secretory factor to activate the development of thermogenic adipocyte. On the other side, recent works also identify some pivotal molecules during thermogenic adipocyte development. These new targets and functional investigation could provide fundamental information for drug development and pre-clinical trial.
2. Metabolic Regulation of Muscle Stem Cell
Skeletal muscle counts for 40% of body weight and is involved in nutrient metabolism such as metals, amino acid, lipid and glucose. Postnatal development and regeneration capacity of muscle stem cell (also called satellite cell) contributes to skeletal muscle growth and maintaining proper function. By taking advantage of chromatin immunoprecipitation, high throughput sequencing and bioinformatics, we identified a group of genes, which may be involved in regulation satellite cell metabolism. By using druggable-target small molecular agonist and antagonist, we are able to recapitulate the phenomena observed in transgenic mouse. This target identification-transgenic mouse phenotype-new drug development pipeline could help us not only understand the physiological function of specific genes but also translate these finds to pre-clinical trials.
3. Biological Function of Gut Microbiota in Metabolic Diseases
Microbiota residing in our body play an essential role in host health and also the disease development and progression. Our laboratory is interested in utilizing the multi-omics to understand how microbiota and their metabolites interact with host and identify signaling interfaces between host and microorganism. Recent works from our group have provided preliminary evidence on diseases early prediction with gut flora. Other works proved that probiotics and their metabolites could alleviate symptoms of several metabolic diseases, such as obesity and type 2 diabetes. Whether these probiotics and their metabolites could be further developed into therapeutic drugs remains to be an open question. Their efficacy and safety need further exploration.
4. Cheminformatics and Bioinformatics based Drug Discovery
Accumulating chem- and biology data provide great opportunity for cheminformatics and bioinformatics-based drug discovery. Our lab could utilize ligand- and structure-based drug design approaches, including similarity searching (2D & 3D), QSAR, docking, pharmacophore, and molecular dynamics simulations to screening active ligands for a specific target. We also develop artificial intelligence (AI) based drug virtual screening tools and drug-related database for the community.