Events

NIH Metabolomics Interest Group

The NIH Metabolomics Interest Group sponsors webinars, seminars, and workshops to highlight recent work in the field.

Upcoming Events

Decoding Host-Microbiota Communication Through Metabolomics November 7, 2017, 10:00-11:00 ET
Webinar

Speaker
Andrew Patterson, PhD, Pennsylvania State University

A complex network of host receptors and microbiota within the gastrointestinal tract work in concert to process and absorb dietary nutrients, detoxify xenobiotics, and establish a homeostatic system that regulates metabolism and inflammation. Emerging evidence suggests ligand-activated transcription factors of the nuclear receptor superfamily and the basic helix-loop-helix/per-arnt-sim (PAS) family not only receive and process chemical signals derived from microbial-dependent metabolic activity, but also transmit these signals to distant organs, including the liver. For example, small intestine signaling of the farnesoid X receptor (FXR), an essential regulator of bile acid, lipid, and glucose metabolism, is modulated through gut microbiome-dependent metabolism of bile acid metabolites produced in the liver. Additionally, studies of the aryl hydrocarbon receptor (AHR), a xenobiotic sensor, have revealed microbial metabolites derived from dietary nutrients including tryptophan as critical regulators of both intestinal and hepatic inflammation. Dissection of the host-metabolite-microbiome interaction was facilitated by use of transgenic mouse models, host and microbiome sequencing, and mass spectrometry- and NMR-based metabolomics. Identification and characterization of microbial metabolites and their relationship with host receptors has begun to provide new avenues for studying host-microbiota communication networks and identifying new therapeutics to modulate this interaction in human disease.

Past Events

Reproducible Global Chemical Analysis of Biology by Mass Spectrometry July 20, 2017, 10:00-11:00 ET
Webinar

Speaker
Pieter Dorrestein, PhD, University of California - San Diego

In the past fifteen years, the cost of mass spectrometry has come down by two orders of magnitude per volume of data that is collected. As the sensitivity of instrumentation increases by an order of magnitude, the number of unknowns doubles. One of the key limitations of untargeted mass spectrometry is the lack of data analysis reproducibility. If the same data is provided to different people, they have different outcomes. The second limitation is our ability to annotate molecules that can be observed. Currently in untargeted metabolomics, on average, only 2% of the data that is collected can be annotated.

To address these shortcomings, a team of investigators, including Dr. Dorrestein, launched a global data driven knowledge sharing and analysis infrastructure called global natural product social molecular networking or GNPS (http://www.nature.com/nbt/journal/v34/n8/full/nbt.3597.html?foxtrotcallback=true). The GNPS community now counts 22,000 users from 128 countries. One of the key features of GNPS is that is allows public sharing of raw data. This is critical for scientific reproducibility and argue that only sharing of tables with m/z, features and annotations is not appropriate. When the raw data is not available, the results tables cannot be updated with the most advanced analysis tools and knowledge. This is important as new algorithms are rapidly advancing.

As of March 2017, there are 910 projects that have raw data in the public domain, more than 500 are contributed by the GNPS community. Within GNPS, one can perform molecular networking and annotate all MS/MS spectra against all publicly available libraries (~240,000 reference spectra) and the libraries contributed by the GNPS community has grown to 40,000. All searches are remembered in your personalized jobs tab and the links of the jobs can be shared in publications and cloned by others to promote reproducibility in the analysis. GNPS also changes the interaction with data. GNPS introduced the living data concept where subscribers to data are periodically updated with the latest knowledge about a given data set.

Finally, Dr. Dorrestein touched on FDR estimation in untargeted metabolomics and visualization tools such as 3D cartography to study the distributions of therapeutics, metabolites of microbial interactions, the microbiome and demonstrate how this may be achieved on clinically relevant time scales.

Dr. Pieter Dorrestein is Professor at the University of California - San Diego. Dr. Dorrestein is trained as a chemist with a focus on understanding how microbes made amino acids, vitamins and other small molecules such as virulence factors, quorum sensors and therapeutically valuable natural products. Currently, Dr. Dorrestein is the Director of the Collaborative Mass Spectrometry Innovation Center and a Co-Director, Institute for Metabolomics Medicine in the Skaggs School of Pharmacy & Pharmaceutical Sciences, and Department of Pharmacology and Pediatrics. Since his arrival to UCSD in 2006, Dr. Dorrestein has been pioneering the development of mass spectrometry methods to study the chemical ecological crosstalk between populations of microorganisms, including host interactions, for agricultural, diagnostic, clinical and therapeutic applications. For a more detailed biography see http://www.nature.com/news/the-man-who-can-map-the-chemicals-all-over-your-body-1.20035.

Nutritional Metabolomics to Identify Biomarkers of Dietary Patterns and Specific Diet Exposures December 6, 2016, 1:00 pm EST
Webinar

Speaker
Mary Playdon, PhD, MPH, National Cancer Institute

Watch the archived video for this webinar.

Healthy dietary patterns are related to lower chronic disease incidence and longer lifespan. However, the precise mechanisms involved are unclear. Furthermore, epidemiologic evidence for associations between dietary factors and breast cancer is weak and, where evidence exists, etiologic mechanisms are also unclear. Identifying biomarkers of dietary patterns and specific dietary exposures may provide tools to validate diet quality measurement, mitigate errors related to self-reported diet, and identify mechanistic mediators.

In two analyses of data from prospective studies, we measured whether four pre-defined diet quality indices (the Healthy Eating Index-2010, the Alternative Mediterranean Diet score, the World Health Organization Healthy Diet Indicator, and the Baltic Sea Diet) were cross-sectionally associated with baseline fasting serum metabolites among 1380 Finnish men participating in the Alpha-tocopherol, Beta-carotene Cancer Prevention Trial, and examined prediagnostically-measured, diet-related metabolites for their association with incident invasive breast cancer among 1,242 post-menopausal women in a nested case-control study within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

For both studies, metabolites were measured using mass spectrometry and diet was measured using validated food frequency questionnaires prior to study randomization. We found that diet quality, measured by healthy diet indices, is associated with serum metabolites. Rather than exerting a unifying metabolic response, the metabolite profiles of each diet index was driven by the components used to score adherence. We also found that prediagnostic serum concentrations of metabolites related to alcohol, vitamin E and animal fats were associated with estrogen receptor positive breast cancer risk.

Mary Playdon, Ph.D., M.P.H., joined the National Cancer Institute’s (NCI) Division of Cancer Epidemiology and Genetics (DCEG) in August 2014 as a predoctoral fellow through the Yale University-NCI Partnership Training Program. She completed a B.S. and an M.P.H. at the Queensland University of Technology, Australia. Dr. Playdon is a registered clinical dietitian, practicing in both Australia and England before coming to the U.S. She was previously Senior Clinical Research Dietitian for the Colorado State University Cancer Prevention Laboratory. Her research interests include nutritional epidemiology, metabolomics and etiology and survivorship of female cancers. In DCEG’s Metabolic Epidemiology Branch (MEB), under the mentorship of Steven C. Moore, Ph.D., M.P.H., investigator, and Rachael Stolzenberg-Solomon, Ph.D., M.P.H., R.D., senior investigator, Dr. Playdon’s dissertation work focused on exploring dietary metabolites as novel biomarkers of dietary intake and their role in breast cancer etiology. As a postdoctoral fellow, Dr. Playdon continues her work on nutritional metabolomics and cancer etiology, and has expanded her portfolio in collaboration with Britton Trabert, Ph.D., M.S., investigator, to include alcohol and obesity exposures and their relationships to hormone metabolism and other female cancers, including endometrial cancer.

Genetics Meets Metabolomics: From Association to Translation November 10, 2016, 10:00 am EST
Webinar

Speaker
Karsten Suhre, PhD, Weill Cornell Medicine-Qatar

Watch the archived video for this webinar.

Genome-wide association studies with concentrations of hundreds of small molecules in samples collected from thousands of individuals (mGWAS) access otherwise inaccessible natural genetic experiments and their influence on the metabolic capacities of the human body. By sampling the natural metabolic and genetic variability that is present in the general population, mGWAS identified so far over 150 associations between genetic variants and variation in the metabolic composition of human body fluids. Associations identified by mGWAS can reveal novel biochemical knowledge, such as the function of uncharacterized genes, the biochemical identity of small molecules, and the structure of entire biochemical pathways. Knowledge of genetic variation in metabolism has many applications of biomedical and pharmaceutical interests, including the functional understanding of genetic associations with clinical end points, design of strategies to correct dysregulations in metabolic disorders and the identification of genetic effect modifiers of metabolic disease biomarkers. mGWAS with growing sample sizes and increasingly complex phenotypic trait panels, such as proteomics and glycomics, are currently being conducted, allowing for more comprehensive and systems-based downstream analyses. In this presentation, Dr. Suhre reviewed work done by his group and collaborators in past and recent mGWAS, discuss extensions to multiomics phenotypes, and outlined possible ways to translate mGWAS findings to clinical and biomedical application.

Dr. Suhre is a Professor of Physiology and Biophysics at Weill Cornell Medicine and the Director of the Bioinformatics and Virtual Metabolomics Core at its branch campus in Doha, Qatar. He holds a Ph.D. in Atmospheric Chemistry and Meteorology from the University of Toulouse III, France, and graduated in Physics from the University of Osnabrück, Germany. Dr. Suhre’s research interests focus on metabolomics and genetic epidemiology, bioinformatics, functional and structural biology. On these subjects, he has taught multiple courses, published over 140 articles in peer-reviewed journals, and delivered numerous international presentations. He established the field of genome-wide association studies of human metabolism, which is reflected in several high-impact publications in the field of which he is the senior author. He is also interested in how genetic variation in human metabolism interacts with environmental challenges and lifestyle factors in the development of complex diseases, including diabetes, heart and kidney diseases, knowing that understanding of the genetic basis of metabolic individuality in humans generates many new hypotheses for biomedical and pharmaceutical research, and can potentially lead to new and individualized therapies. Dr. Suhre is currently involved in setting up clinical studies in cooperation with different health organizations in Qatar, including diabetes and cancer, which centrally involve his specific expertise in the field of metabolomics.

Nutritional Metabolomics to Identify Biomarkers of Dietary Patterns and Specific Diet Exposures and its Application to Understanding Breast Cancer Etiology August 18, 2016, 2:00 pm EST
Main Campus, Building 37, Room 6041/6107

Speaker
Mary Playdon, PhD, MPH, National Cancer Institute

Healthy dietary patterns are related to lower chronic disease incidence and longer lifespan. However, the precise mechanisms involved are unclear. Furthermore, epidemiologic evidence for associations between dietary factors and breast cancer is weak and, where evidence exists, etiologic mechanisms are also unclear. Identifying biomarkers of dietary patterns and specific dietary exposures may provide tools to validate diet quality measurement, mitigate errors related to self-reported diet, and identify mechanistic mediators.

In two analyses of data from prospective studies, we measured whether four pre-defined diet quality indices (the Healthy Eating Index-2010, the Alternative Mediterranean Diet score, the World Health Organization Healthy Diet Indicator, and the Baltic Sea Diet) were cross-sectionally associated with baseline fasting serum metabolites among 1380 Finnish men participating in the Alpha-tocopherol, Beta-carotene Cancer Prevention Trial, and examined prediagnostically-measured, diet-related metabolites for their association with incident invasive breast cancer among 1,242 post-menopausal women in a nested case-control study within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

For both studies, metabolites were measured using mass spectrometry and diet was measured using validated food frequency questionnaires prior to study randomization. We found that diet quality, measured by healthy diet indices, is associated with serum metabolites. Rather than exerting a unifying metabolic response, the metabolite profiles of each diet index was driven by the components used to score adherence. We also found that prediagnostic serum concentrations of metabolites related to alcohol, vitamin E and animal fats were associated with estrogen receptor positive breast cancer risk.

Mary Playdon, Ph.D., M.P.H., joined the National Cancer Institute’s (NCI) Division of Cancer Epidemiology and Genetics (DCEG) in August 2014 as a predoctoral fellow through the Yale University-NCI Partnership Training Program. She completed a B.S. and an M.P.H. at the Queensland University of Technology, Australia. Dr. Playdon is a registered clinical dietitian, practicing in both Australia and England before coming to the U.S. She was previously Senior Clinical Research Dietitian for the Colorado State University Cancer Prevention Laboratory. Her research interests include nutritional epidemiology, metabolomics and etiology and survivorship of female cancers. In DCEG’s Metabolic Epidemiology Branch (MEB), under the mentorship of Steven C. Moore, Ph.D., M.P.H., investigator, and Rachael Stolzenberg-Solomon, Ph.D., M.P.H., R.D., senior investigator, Dr. Playdon’s dissertation work focused on exploring dietary metabolites as novel biomarkers of dietary intake and their role in breast cancer etiology. As a postdoctoral fellow, Dr. Playdon continues her work on nutritional metabolomics and cancer etiology, and has expanded her portfolio in collaboration with Britton Trabert, Ph.D., M.S., investigator, to include alcohol and obesity exposures and their relationships to hormone metabolism and other female cancers, including endometrial cancer.

Stable Isotope-Resolved Metabolomics as a Tool for Understanding Kidney Cancer Metabolism June 7, 2016, 3:00 pm EST
Main Campus, Building 37, Room 4107

Speaker
Dan Crooks, PhD, National Cancer Institute

Once thought of as a single disease, renal cell carcinoma (RCC) is now known to be several different types of cancer that are characterized by different genetic mutations, histologies, and responses to therapy. Many gene mutations in kidney cancer are known to have a direct and profound effect on cell metabolism, including oxygen sensing by the HIF pathway (VHL), nutrient sensing via the mTOR and other pathways (FLCN, MET, TFE3), and energy sensing as a result of direct disruption of the Krebs cycle (FH, SDH). We are utilizing stable isotope-resolved metabolomics (SIRM) to investigate altered metabolism in patient-derived cultured RCC cells, tumor xenografts in mice, thin tissue slices obtained during surgery, and intraoperative 13C-glucose infusion in patients to explore the unique metabolic phenotypes associated with the various genetic lesions that cause kidney cancer in humans. Untargeted isotopologue distributions in polar and non-polar metabolites are determined in extracts of cancer and normal kidney using 1H and 13C NMR spectroscopy and multiple mass spectrometry modalities to define the metabolic reprogramming in different RCCs. Preliminary analyses in fumarate hydratase (FH)-deficient patient tumors and cells have demonstrated that FH-deficient tumors contain a significant pool of fumarate that is not derived directly from the Krebs cycle via the succinate dehydrogenase reaction. These findings are being used to evaluate the effect of novel therapeutic approaches for kidney cancer that are tailored to the distinctive metabolism and genotype found in the diverse array of genetically-defined kidney cancers.

Dr. Crooks studies kidney cancer metabolism in the laboratory of W. Marston Linehan at the NCI Urologic Oncology Branch in the NIH Clinical Center, with the goal of identifying novel metabolic pathways that can be targeted by therapeutics in the clinic. Dr. Crooks is learning to apply Stable Isotope-Resolved Metabolomics (SIRM) techniques to study cell metabolism through a collaboration with Drs. Teresa Fan and Andrew Lane at University of Kentucky. He completed a B.A. in Molecular Biology and an M.S. in Environmental Toxicology at the University of California at Santa Cruz, and earned a Ph.D. in Biochemistry from Georgetown University while performing research at the NIH on cellular iron metabolism in developing red blood cells and in mitochondrial myopathy patients. His long-term research interests lie in developing new metabolomics techniques to study altered cellular metabolism and tissue specificity in human diseases.

Metabolomics of Blood Pressure Regulation May 24, 2016, 10:00 am EST
Webinar

Speaker
Cristina Menni, PhD, King’s College London

Watch the archived video for this webinar.

Hypertension represents a major global disease burden but discovering molecular mechanisms underlying blood pressure (BP) regulation has been challenging. During this webinar, Dr. Cristina Menni described research using a metabolomics and interventional approach to identify novel metabolite markers for BP and BP phenotypes that were significantly associated with both BP and mortality. Evidence for a causal role was obtained in an animal model experiment that resulted in significant increases in BP, indicating that it was not a byproduct, but a cause of high BP. This research has also identified other metabolites strongly associated with cardiovascular traits.

Dr. Cristina Menni is a Research Fellow in the Twin Research & Genetic Epidemiology Department at King’s College London. She received her Master in Mathematics from the University of Cambridge and her Ph.D. in statistics from the University of Milan-Bicocca where she specialized in statistical genetics. Dr. Menni’s research is focused on identifying novel molecular markers associated with ageing and age-related diseases such as hypertension using metabolomics in conjunction with several other "omics" datasets. She has co-authored over 40 scientific articles in peer reviewed journals. She is involved in the data quality control, analysis, and interpretation for various European Union and Medical Research Council projects within King's College London.