Xianlin Han's Research Focus
The interests of Dr. Han’s laboratory have been focused on the altered lipid metabolism, trafficking and homeostasis under patho(physio)logical conditions. Currently, there are three specific areas explored in his laboratory: (1) extension of the shotgun lipidomics technology for increased penetrance into the low abundance regime of a cellular lipidome with emphasis on high throughput, and bioinformatics; (2) investigation of the biochemical mechanisms underlying the altered lipid content and composition in metabolic syndrome; and (3) identification of the biochemical mechanisms responsible for the sulfatide depletion and ceramide elevation at the very earliest stages of Alzheimer’s disease.
Xianlin Han's Research Report
Shotgun Lipidomics Technology, Cellular Lipidome, High Throughput and Bioinformatics
Multi-dimensional mass spectrometry-based shotgun lipidomics that we have developed allows us to quantitatively analyze over 20 lipid classes, approximately 95 percent of the content and hundreds to thousands of lipid molecular species of a cellular lipidome directly from a lipid extract of a biological sample. However, shotgun lipidomics needs to be further developed, refined and/or extended for its penetrance into the low abundance regime of a cellular lipidome or uncovered lipid classes with high throughput and bioinformatics. Particular interests at the moment will be in the sphingolipid classes and molecular species.
Biochemical Mechanisms, Lipid Content and Metabolic Syndrome
Our recent studies by shotgun lipidomics have revealed numerous alterations in lipid content and composition including cardiolipin, acyl-CoA, acylcarnitine and triacylglycerol in numerous organs at the diabetic and/or obesity states. Accordingly, our research goal in this area is to identify the biochemical mechanism(s) underlying these altered lipid profiles and the causal roles of the altered lipid content and composition in metabolic dysfunction compromising diabetes and obesity. We will utilize a specific set of murine genetic models and the state-of-the-art shotgun lipidomics technology to address these research goals.
Biochemical Mechanisms, Sulfatide Depletion and Alzheimer's Disease
Through utilization of the enabling technology of shotgun lipidomics, we have recently revealed that a specific myelin sphingolipid, sulfatide, is substantially depleted at the very earliest clinically-recognizable stage of Alzheimer’s disease. In addition, we have uncovered that in the central nervous system: 1) sulfatides are specifically associated with apolipoprotein E (apoE)-containing high-density lipoprotein-like particles in cerebrospinal fluid; 2) apoE modulates cellular sulfatide levels; and 3) the modulation of sulfatide content is apoE-isoform dependent. Based on these findings, we have proposed a working model of sulfatide depletion in the pathogenesis of Alzheimer’s disease where Abeta peptide clearance/deposition and apoE serve as synergistic risk factors. Through exploiting the sensitivity and specificity of mass spectrometry in conjunction with novel mechanistic hypotheses and experimental designs as well as utilization of other state-of-the-art technologies (e.g., confocal fluorescence microscopy, real-time PCR, proteomics, etc.), we have generated intense interest in the roles of specialized lipids in the pathobiology of Alzheimer’s disease. In the future, we will further explore the roles of specialized lipids (e.g., sulfatide, ceramide, plasmalogen, and gangliosides) in Alzheimer’s disease as well as in other neurodegenerative diseases and neurological disorders.
Xianlin Han's Bio
Xianlin Han, M.S., Ph.D., received his M.S. degree in Physical Chemistry at Zhejiang University, China, and his Ph.D. in Biophysical and Bioanalytical Chemistry at Washington University in St. Louis. Prior to joining Sanford-Burnham, Dr. Han was an Associate Professor of Medicine, a faculty member at the Center for Cardiovascular Research in the Department of Internal Medicine, Washington University in St. Louis, a faculty member of the Division of Biology and Biomedical Sciences, and serves as a member of the Executive Committee of the Alzheimer’s Disease Research Center, Washington University School of Medicine. Dr. Han is particularly interested in identifying the biochemical mechanism(s) underlying the altered lipid metabolism, trafficking, and homeostasis under patho(physio)logical conditions by using a lipidomics approach. Dr. Han is one of the pioneers in lipidomics.