Lipid Leaders Interview Series: Dr. Xianlin Han discusses neurolipidomics

Posted on April 17, 2023

Xianlin Han Lipid Leaders

Attention all science enthusiasts and researchers! Are you curious about the groundbreaking field of lipidomics and how it can revolutionize the healthcare industry? Look no further than our upcoming Explore the Lipidome webinar series, starting in just under a month!

We are excited to announce that the esteemed Dr. Xianlin Han will be joining us for the first installment of the series, and as our Lipid Leader of the month. In an exclusive interview, Dr. Han will share his expertise on shotgun lipidomics, a cutting-edge technique that enables the analysis of hundreds of lipids at once.

Join us as we delve deeper into the exciting world of lipidomics, and discover the challenges and potential solutions facing the translation of lipidomics into the clinic. Don't miss out on this unique opportunity to learn from a renowned expert and gain insights into the future of lipidomics research. Mark your calendars and tune in for this exciting event! Read the full interview with Dr. Xianlin Han below!

Tell us a little bit about yourself.

    I graduated from the department of chemistry at Zhejiang University, China in 1982 and further received my M.S. degree there. I received my Ph.D. in biophysical chemistry and did my post-doc training both in Dr. Richard Gross’ lab in Washington University School of Medicine. I joined the Division of Bioorganic Chemistry in Washington University School of Medicine as a research faculty from 1992 to 2000. I became a tenure-tracked assistant professor of medicine there in 2000 and was promoted to associate professor of medicine with tenure in 2008. I was a professor in the Programs of Cardiovascular Metabolism & Integrative Metabolism at Sanford Burnham Prebys Medical Discovery Institute between 2010 and 2017. I am now a professor of medicine, and an endowed chair in aging studies and research at the Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio (UTHSA). I have received honorary guest professorship from multiple Institutes/Universities in China, including Soochow University, Ocean University of China, Zhejiang Chinese Medical University, and Changchun Institute of Applied Chemistry, Chinese Academy of Sciences. I am currently serving as the director for functional lipidomics core at UTHSA, the leader of Biomarker Core in the South Texas Alzheimer Research Center, and the leader of Cellular and Integrated Physiology of Aging Core in San Antonio Nathan Shock Center. I served as the President of Chinese American Society for Mass Spectrometry and now I am a member of the Society’s Board of Directors. I serve as the secretory of International Lipidomics Society. I served as an appointed member of NIH study sections and ADA Research Grant Review Committee, and serve as an external reviewer of Hong Kong Research Grants Council.

    I am one of the pioneers in lipidomics and the inventor of shotgun lipidomics technologies. I have published over 350 peer-reviewed research articles. I am the author of the book “Lipidomics: Comprehensive Mass Spectrometry of Lipids” and the co-author of the book “Lipid Analysis (4th Edition)” with Dr. William W. Christie, a Fellow of the Royal Society of Edinburgh. I serves as the associate editor of “Journal of Lipid Research” and as a member of the editorial board of numerous international journals including Analytica Chimica Acta, “Molecular and Cell Biology of Lipids” in Biochimica et Biophysica Acta, Life Metabolism, and Proteomics. I have organized numerous lipidomics-related symposia and workshops and edited several special issues on lipidomics in analytical and lipid journals, such as Analytica Chimica Acta and Journal of Lipid Research.

    You are a pioneer in the field of shotgun lipidomics and have continued publishing research in this area since many new separation-based approaches have been developed. What advantages do you see with shotgun lipidomics over other lipidomics approaches?

      There exist many advantages with our shotgun lipidomics technology, termed “multi-dimensional mass spectrometry-based shotgun lipidomics”. The details of these advantages have been extensively discussed in a few of my invited review articles published in Mass Spectrometry Review and my book “Lipidomics: Comprehensive Mass Spectrometry of Lipids”. One of the primary adavantages possessed by shotgun lipidomics is that analysis of a class/category of lipids can be achieved under a constant condition including lipid concentration. Such a condition is crucial for accurate quantification of lipids by mass spectrometry. Another primary adavantage of shotgun lipidomics is to readily control the lipid concentration below the threshold to form aggregation. Avoiding lipid aggregation is essential for lipid analysis, whereas lipids can form aggregation virtually in all solvents, particularly in polar solvents. Lipids present in aggreagated forms are not only unable to be quantified (unless an isotope labeled standard is coexisting), but also introduce many artifactual ion peaks. Ion suppression is an issue by using shotgun lipidomics. Many approaches can be used to solve this issue as previously discussed (PMID: 31291508).

      When it comes to multi-omics data, how useful do you think having different types of data sets for the same sample can be? Do you think performing multi-omic analysis (e.g. lipidomics, transcriptomics, proteomics) on a sample can lead to an excess of data that might make drawing conclusions difficult?

        How many omics datasets should be acquired for a project really depends on the purpose of the study. If for lipid biomarker discovery and development, then a lipidomics dataset is good enough. However, if someone would like to understand a question from molecular and/or cellular levels, i.e., reveal the underlying molecular mechanism related to a lipid phenotype, then two types of omics analyses would be necessary. For example, in our functional lipidomics studies, we usually conduct transcriptomics in addition to lipidomics. I agree, multi-omics integration is challenging, but should facilitate problem solving.

        What are some of the advantages and disadvantages of studying organoids? Do you think we will be seeing more researchers using organoids in the future?

          There are many advantages to study organoids, e.g., to model some in vivo biological processes, to use a limited supply of starting materials, to effectively develop therapies, to study cell cell interactions in a closely-related microenvironment, etc. However, we do not totally understand the cellular microenvironments, and many functions are beyond three-dimensional cell models. I believe this research front will be paid more and more attension and the applications of organoid research should become more broader.

          What do you think is the biggest obstacle for translating lipidomic findings into the clinic?

            The main obstacle surrounding this issue is whether the lipidomics findings can be generally replicated and validated to a certain degree. At the current stage of lipidomics development, we still face a big challenge to accurately identify and quantify lipid molecular species. Many of the lipidomics findings were unable to be replicated. Therefore, one of the tasks in the lipidomics community is to make lipidomics analysis standardized.

            What do you consider to be the greatest breakthrough in lipid research in recent years?

              I would not say we have a greatest breakthrough in lipid research in recent years, but clearly, we have seen advances in multiple areas in lipid research. Examples include, but are not limited to, lipidomics in combination with AI/machine learning in predicting disease(s) at their early stages; identification of multiple lipid metabolism-related genes associated with Alzheimer’s disease; and real-time monitoring lipid metabolism at the cellular and systemic levels.

              What is the best piece of advice you have ever received from someone?

                I received many advices in my career. What I like the most and also I give to my trainees is the one that “you need to be prepared for”. We know there exist many opportunities in science discovery, but the chances are largely given to those who are well prepared.