Research

Integration of Methods

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Ongoing Programs

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Obesity-related Melanocortin-4 Receptor

Melanotropins,which include melanocyte-stimulating hormones (α-,β-,and γ-MSH) and adrenocorticotropic hormone (ACTH),exert their function through five subtypes of melanocortin receptors (MCRs). The MC4 receptor subtype which is mainly expressed in central nervous system (CNS),is known as its role on regulation of food behavior and defective human MC4R gene is most common cause of monogenic obesity. In this project,we focus on atomic scale to comprehend MC4 receptor. Our goal is to solve MC4R structure in active and inactive states by both X-Ray and Cryo-EM.

 

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Glucagon like peptide 1 receptor

GLP-1 is a peptide hormone which exerts important actions in the management of type 2 diabetes mellitus and obesity. The structural study of GLP-1R will provide useful information for new diabetes drugs design. Recently,two complex structures of GLP-1R bound to GLP-1,Ex-p5 and Gs protein was determined by Cryo-EM and a crystal structure of GLP-1R bound to peptide 5 was determined by X-ray. However,the molecular interactions between ligand and protein aren’t very clear. In our study,we have developed a series of stable constructs which when combined with certain ligands generated a stable full-length GLP-1R sample that is sufficient for crystallography works and initiate cryo-EM studies. Ultimately,we devote to determine the high resolution (>3.5 A) structure of full-length GLP1R which will lead to more efficacious drugs to treat T2DM and obesity.

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Oxygen to Glucose Index (OGI) Using PET/MR for Quantitative Aerobic Glycolysis Mapping

In many cases,cerebral metabolism is altered among people with neurological diseases,which makes it possible to take the ratio between regional consumption of oxygen and glucose as a diagnostic biomarker.This project is trying to use PET/MRI system to obtain the cerebral metabolism rate of oxygen consumption and the cerebral metabolism rate of glucose consumption during the resting state,calculating the oxygen to glucose index (OGI),for quantitative aerobic glycolysis mapping.

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Tomographic characterization of pancreatic beta cell insulin secretory pathway

Diabetes mellitus, one of the most popular modern diseases, is triggered by insulin metabolic disorders inside Pancreatic Beta cells (PBC), the only type of cells in human body that can synthesize and secrete insulin. By the use of soft X-ray tomographic techniques, we are able to gain novel insights of the cell organization at the mesoscale level, where the cell behavior can be rationalized, quantified and predicted, to observe the rearrangement of the insulin granules (ISG) under different physiological conditions. Analysis of ISGs and other organelles localization would benefit us to have better understanding of biological process at the ground of the insulin release and glucose homeostasis.