Unit of Integrative Metabolomics
The focus of our research is to understand the metabolic drivers of disease towards the goal of developing a quantitative phenotype of health.
Our work employs mass spectrometry to perform molecular phenotyping of individuals in response to disease or environmental stressors. These efforts are combined with integrative modeling to identify biochemical pathways associated with specific disease sub-phenotypes towards the twin goals of understanding the etiology of disease processes and identifying markers of the onset as well as resolution of system-based stress.
Research areas in the Unit are centered on:
We are working to develop the nascent discipline of metabolomic epidemiology, the field involving the systematic use of epidemiological methods and principles to study population-based variation in the human metabolome as it associates with health-related outcomes or exposures. Towards that end, the group works extensively on developing high-throughput robust metabolomics methods that are suitable for large-scale data acquisition. As part of our efforts in this area, we work to address many of the issues that can serve as potential sources of study bias and variation, both epidemiological and metabolomic, including study design, metadata collection, patient selection, appropriate choice of biofluid/tissue, sample collection, biobanking protocols, sample storage integrity, metabolite coverage, metabolite annotation, and metabolite quality control. Accordingly, following collection and analytical consideration of these potentially influencing variables, metabolomic and epidemiological data are integrated, and appropriate interpretations can be made. These efforts are important for our work in stratified or precision medicine in which we can use individual metabotypes to identify patient sub-groups with unique disease trajectories and treatment needs towards the goal of getting the right medication to the right patient at the right time. Our primary interest is in understanding the pathophysiological and environmental drivers of obstructive lung disease with a focus on asthma, in which we are using metabolomic epidemiological approaches to identify biomarkers for stratifying asthmatics for treatment with biologics.
We are investigating the role of bioactive lipids including octadecanoids, eicosanoids, and sphingolipids in the etiology and pathophysiology of inflammation. Our research focuses in particular on the C18-carbon containing fatty acids and their downstream biosynthetic products. Linoleic acid, and its C18 analogs from both omega-6 and omega-3 fatty acids, can be converted to multiple metabolites, collectively called octadecanoids. While there is extensive research on the biological activity of the arachidonic acid-derived eicosanoids, there is a paucity of information on the octadecanoids. This oversight is important because due to the widespread use of vegetable oils, linoleic acid is now the most highly consumed polyunsaturated fatty acid (PUFA) in the western diet. The increase of linoleic acid consumption over the last 50 years has raised concerns concerning its potential impact upon human pathophysiology, particularly in regards to the effects on chronic inflammation. Conversely, the omega-3 fatty acid alpha-linolenic acid (ALA) is generally considered to exert anti-inflammatory or pro-resolving effects, and deficiencies are associated with onset of inflammation. Work in our group focuses on identifying new octadecanoids and developing the analytical methods to quantify these compounds in multiple biological matrices. We focus in particular on characterizing the production of octadecanoids by immune cells to explore their role in the etiology of obstructive lung disease. Recent efforts include investigating the role of the gut microbiome in the production of octadecanoids and examining their physiological role in the gut-lung axis. Our primary interest can be summarized as a concerted effort to quantify lipids with a focus on understanding the role of fatty acids and their lipid mediator biosynthetic produ