Gary Patti, Ph.D.

Michael and Tana Powell Associate Professor
Chemistry
Genetics

Computational and Systems Biology Program
Biochemistry, Biophysics, and Structural Biology Program
Neurosciences Program

  • 314-935-3512

  • 1134

  • gjpattij@wustl.edu

  • http://pattilab.wustl.edu/

  • metabolism, metabolomics, mass spectrometry, bioinformatics, imaging, cancer, tumor microenvironment, isotope tracing

  • To understand the metabolic crosstalk between cells and tissues in disease models such as cancer by using isotopes and metabolomics

Research Abstract:

Our research program has three major components. Each is briefly summarized below.

(i) Metabolomics technology development
We are developing experimental platforms that involve one or more of the following: mass spectrometry, stable isotope tracing, mass spectrometry-based imaging, whole-cell or intact tissue NMR, and genetic engineering. We seek to improve annotation of signals, develop reference datasets, identify new molecules or pathways, and establish platforms that allow metabolism to be resolved at the cellular level from bulk tissue specimens.

(ii) Creating bioinformatic resources to process metabolomic data
It is now routine to measure thousands of signals in a mass spectrometry-based metabolomic experiment. Yet, to date, only a small fraction of those signals have been biochemically named in any one experiment. This creates significant hurdles for data processing, especially for less experienced researchers. We have found that one challenge is the large number of artifacts and contaminants in many metabolomic experiments. We are building resources to identify these and remove them, ideally in real time during data acquisition.

(iii) Understanding how metabolism supports growth in cells, tumors, and animals
Growth requires the generation of biomass in the form of proteins, DNA, lipid membranes, etc. We are interested in how cells reprogram their metabolism (or organismal metabolism) to support such anabolic needs. Notably, growth not only changes nutrient-uptake rates but also the pathways in which the nutrients are routed. We are particularly focused on metabolic pathways that paradoxically get activated during growth in the absence of conventional stimuli (e.g., fermentation without hypoxia, lipid synthesis without ATP surplus, glucose uptake during starvation, etc.).

Selected Publications:

Yao C-H, Liu G-Y, Wang R, Moon SH, Gross RW, and Patti GJ
Identifying Off-Target Effects of Etomoxir Reveals that Carnitine Palmitoyltransferase 1 is Essential for Cancer Cell Proliferation Independent of B-Oxidation
PLOS Biology, 16(3):e2003782, 2018

Gelman SJ, Naser FJ, Mahieu NG, McKenzie LD, Dunn GP, Cheeda MG, and Patti GJ
Consumption of NADPH for 2-HG Synthesis Increases Pentose Phosphate Pathway Flux and Sensitizes Cells to Oxidative Stress
Cell Reports, 22, 512-522, 2018

Mahieu NG and Patti GJ
Systems-Level Annotation of a Metabolomics Data Set Reduces 25,000 Features to Fewer than 1,000 Unique Metabolites
Anal. Chem., 89(19), 10397-10406, 2017

Chen Y-J, Mahieu NG, Huang X, Singh M, Crawford PA, Johnson SL, Gross RW, Schaefer J, and Patti GJ
Lactate Metabolism is Associated with Mammalian Mitochondria
Nature Chemical Biology, 12, 937-943, 2016

Mahieu NG, Spalding J, Gelman S, Patti GJ
Defining and Detecting Complex Peak Relationships in Mass Spectral Data: The mz.unity Algorithm
Anal. Chem., 88(18), 9037-9046, 2016

Yao C-H, Grider RF, Mahieu NG, Liu G-Y, Chen Y-J, Wang R, Singh M, Potter GS, Gross RW, Schaefer J, Johnson SL, Patti GJ
Exogenous Fatty Acids Are the Preferred Source of Membrane Lipids in Proliferating Fibroblasts
Cell Chemical Biology, 23, 1-11, 2016

Spalding J, Cho K, Mahieu NG, Nikolskiy I, Llufrio EM, Johnson SL, Patti GJ
Bar Coding MS2 Spectra for Metabolite Identification
Anal. Chem., 88(5), 2538-2542, 2016

Mahieu NG, Spalding S, Patti GJ
Warpgroup: Increased Precision of Metabolomic Data Processing by Consensus Integration Bound Analysis
Bioinformatics, 32(2), 268-275, 2016

Zamboni N, Saghatelian A, Patti GJ
Defining the Metabolome: Size, Flux, and Regulation
Molecular Cell, 58(4), 699-706, 2015

Patti GJ, Yanes O, Siuzdak G. Metabolomics: The Apogee of the Omic Triology. Nature Reviews 2012 13: 263-269.

Last Updated: 7/25/2018 8:19:14 AM

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