Biomedical Research

Impact of environmental tobacco smoke on perinatal lung metabolism (NIH  R01 ES013932)

This project is a 5-year collaborative effort between the Fiehn laboratory and environmental health researchers (Kent Pinkerton, CHE at UC Davis and Jesse Joad, UC Davis Medical School) to characterize the development of asthmatic-type respiratory malfunctions in newborn and young adult rats, caused by environmental tobacco smoke (ETS).

Diagnosis and prediction of individual responses of human patients to pharmaceutical drugs (NIH GM078233) 

Our metabolomics platform (comprising GC-TOF mass spectrometry, LC-MS and FT-MS) together with in-house developed databases, open source and commercial software facilitates a comprehensive evaluation of changes in the composition of small molecules in blood plasma and tissue. Led by Dr. Rima Kaddurah-Daouk (Duke University), we are part of a 4-year U.S. national consortium to utilize metabolic signatures to diagnose and predict the responses of individual patients to drug therapies, particularly for bipolar disorders.

Breast cancer biomarkers based on integrated metabolomics (European Union FP7 Health-2007-2.1.4.1 project 200327) 

Breast cancer is the most common cancer in women. Unlike genetic markers or mRNA transcripts, changes in metabolite levels have not been studied to a great extent with respect of insights into cellular dysregulation of breast cancer cells or use of metabolic profiles to diagnose and predict breast cancer tumor development and progression. The Fiehn laboratory contributes to a 3-year project of an eight-partner European consortium focusing on this disease by delivering standardized metabolic readouts and extension of our current databases. In addition, we  will  work towards  structural annotation of biomarkers using advanced query tools. 

Identification of Muscle-Specific Biomarkers of Fatty Acid beta-Oxidation (NIH R01 DK078328) 

Elevated fat levels within skeletal muscle cells (intramyocellular lipids) are highly correlated with muscle and whole-body insulin resistance, and more prevalent in obesity. Reduced muscle mitochondrial fatty acid beta-oxidation is more prevalent among insulin-resistant/diabetic persons. Led by Principal Investigator Sean Adams of the USDA-Western Health Nutrition Research Center in Davis, this project will identify specific biomarkers of muscle fatty acid beta- oxidation using multiple metabolomic analytical platforms to compare metabolite profiles in isolated mitochondrial organelles, in muscle cells that are catabolizing tatty acids at different rates, in a transgenic animal model, and in human subjects harboring a truncation polymorphism. This project will further determine whether metabolomic profiles reflective of muscle fat combustion predict metabolic health changes following diet and exercise intervention in obese subjects.

Plant Research

Real-time detection of citrus plant responses to pathogen infection by analysis of volatile emissions (UC Discovery itl07-10167)

          The California citrus fruit industry is threatened by various pathogen diseases, some of which could have devastating
          consequences if the pathogens reach the state and remain undetected. Led by Dr. Abhaya Dandekar (UC Davis Plant
          Sciences), the Fiehn laboratory will team up with plant biologists and engineers to develop a database of volatile
          emissions that enables a clear distinction of infected and healthy citrus plants, in addition to understanding the
          underlying regulatory mechanisms that lead to volatile emissions under pathogen attack.          

Functional genomics in Arabidopsis thaliana   (NSF MCB 0520140, completed)

The Fiehn laboratoy was part of a 2-year U.S. national project led by Dr. Basil Nikolau, Iowa State University, to demonstrate that metabolic functions of orphan genes can be characterized by metabolomics  screening. All data acquired in this consortium can be freely downloaded here (requiring just a simple registration).

Chlamydomonas metabolism   (Agilent University Relations program)

We utilize the unicellular green algae Chlamydomonas reinhardtii to study fundamental problems in metabolism of photoautotrophic organisms. Causal connectivity in metabolic networks is investigated by a different degrees of nutritional deprivation in a time-dependent manner. We are integrating metabolomic and proteomic analyses to study biochemical responses upon environmental stimuli or genetic differences.

Botryococcus braunii for biofuel research

Botryococcus braunii is a green colonial microalgae found worldwide in freshwater. This algae is of importance because if its ability to synthesize huge amounts of lipids (60-70%). These lipids can be converted to biodiesel or gasoline. We investigate the active metabolism of these algae in time series experiments under various nutrients depletions conditions.

Informatics and Technology Research

SetupX and BinBase

Two databases developed in the Fiehn laboratory steer laboratory workflows, process mass spectrometry raw data and  disseminate result data. SetupX hosts study design metadata that define the biological objects, treatments and time points of a study as well as experimental metadata such as sample preparation and mass spectrometry methods. Laboratory assistants use SetupX to download and randomize sequence tables for the mass spectrometers. After data acquisition, a relational database system (BinBase) is employed for automated metabolite annotation using a multi-tiered filtering system to retain only high quality and consistent metabolite peaks. Results are exported back to SetupX for downloads. Most studies are still not publicly available, mostly because the results have not yet been published in peer-reviewed scientific journals.

Mass spectral libraries of identified compounds                    (sponsored by mass spectrometry vendors)

Annotation of unknown metabolites by mass spectrometry and database queries    
                          (initiated by a DuPont donation, now sponsored by European Union FP7 Health-2007-2.1.4.1 project 200327)

Evaluation of new analytical phases for liquid chromatography

Together with Professor Nobou Tanaka's group in Japan we test and evaluate newly developed monolithic capillary columns for liquid chromatography. These columns are available as hydrophilic interaction (HILIC), ion exchange, and reversed phase (RP) mode capillary columns. Monolithic columns show a superior performance compared to particle columns.