Gary Patti

Gary Patti

Dean's Fellow for Advancement and Entrepreneurship
Senior Director, Center for Metabolomics and Isotope Tracing
Director, Clinical Research Core in Medicine
Director, Faculty Affairs in Chemistry
Professor of Chemistry and of Genetics and Medicine (School of Medicine)
Michael and Tana Powell Professor of Chemistry
research interests:
  • Cancer
  • Computational Biology
  • Metabolomics
  • Zebrafish
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    • Washington University
    • MSC 1134-196-525
    • One Brookings Dr.
    • St. Louis, MO 63130-4899
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    Professor Patti's research is focused on metabolism. His laboratory's work spans three complementary themes. 

    Cancer Biology 

    Cancer cells have the capacity to proliferate uncontrollably. With each division cycle, a cell’s entire contents must be synthesized. The Patti laboratory studies how metabolism is adapted to support the anabolic demands of proliferation, with the ultimate goal of discovering therapeutics that target tumor growth.

    Work from the Patti group has shown that oncogenic transformation not only alters the metabolism of the malignant cell, but that it also has the ability to rewire the metabolism of healthy cells throughout the host. In some cases, a single tumor can hijack the metabolism of a tissue on the other side of the organism for its own benefit. One of the Patti lab's major goals is to understand how and why this occurs. They speculate that tumors co-opt healthy cell metabolism to obtain metabolic precursors in support of proliferation. Accordingly, they wish to define which nutrients are exchanged between which cells and tissues. To this end, the Patti laboratory works with various cancer models including mice and zebrafish. 

     

    Technology Development 

    The Patti laboratory is motivated to develop new tools that provide insight into previously intractable biological questions. A primary interest is in advancing the fields of metabolomics, lipidomics, and exposomics. The Patti group seeks to leverage these approaches to perform population-level profiling of cohorts comprised of thousands of individuals and to integrate the results with other omics data such as transcriptomics, whole genome sequencing, ATAC-seq, and proteomics. Additionally, they leverage stable isotopes to assess metabolic fluxes and inter-tissue interactions. Beyond using established techniques, they are also developing new isotope-tracing methods to encode unique metabolic information such as cellular or organelle provenance. They complement LC/MS experiments with multiplexed imaging of transcripts, proteins, and metabolites. Using MALDI and DESI based approaches along with CODEX and spatial transcriptomics, the Patti laboratory aims to resolve metabolic processes within individual cells of tissues. A major goal is to advance single-cell metabolomics and isotope tracing.

    Computational Biology 

    Metabolomics, lipidomics, and exposomics experiments generate large volumes of data. The rate-limiting step of interpretation is data processing. Currently, the biggest barrier is that the majority of peaks in a standard experiment do not correspond to unique biological molecules. Rather, they originate from contaminants, artifacts, and signal redundancies. The Patti laboratory is committed to establishing user-friendly software tools for complete annotation of datasets, particularly those signals without biological relevance. They leverage insights from their annotation results to improve upon data-acquisition strategies, often in close collaboration with instrument manufacturer companies.

    To process isotopically labeled samples and compute metabolic fluxes, the Patti group develops additional tools. First, they assess labeling dynamics in products downstream of the tracer. They then input these results into mathematical models that they build on the basis of chemical transformations in metabolic pathway diagrams.

    Selected Publications

     

    Schwaiger-Haber M, Stancliffe E, Anbukumar DS, Sells B, Yi J, Cho K, Adkins-Travis K, Chheda MG, Shriver LP, Patti GJ: Using Mass Spectrometry Imaging to Map Fluxes Quantitatively in the Tumor Ecosystem. Nature Communications, 14(1): 2876, 2023. 

     

    Niu X, Stnacliffe E, Gelman SJ, Wang L, Schwaiger-Haber M, Rowels JL 3rd, Shriver LP, Patti GJ: Cytosolic and Mitochondrial NADPH Fluxes Are Independently Regulated. Nature Chemical Biology. 19(7): 837-845, 2023. 

     

    Stancliffe E and Patti GJ: PeakDetective: A Semisupervised Deep Learning-Based Approach for Peak Curation in Untargeted Metabolomics. Analytical Chemistry, 95(25): 9397-9403, 2023. 

     

    Wang Y, Stancliffe E, Fowle-Grider R, Wang R, Wang C, Schwaiger-Haber M, Shriver LP, Patti GJ: Saturation of the Mitochondrial NADH Shuttles Drives Aerobic Glycolysis in Proliferating Cells. Molecular Cell, 82(17): 3270-3283.e9, 2022. 

     

    Stancliffe E, Schwaiger-Haber M, Sindelar M, Patti GJ: DecoID Improves Identification Rates in Metabolomics through Database-Assisted MS/MS Deconvolution. Nature Methods, 18(7): 779-787, 2021.

     

    Naser FJ, Jackstadt MM, Fowle-Grider R, Spalding JL, Cho K, Stancliffe E, Doonan SR, Kramer ET, Yao L, Krasnick B, Ding L, Fields RC, Kaufman CK, Shriver LP, Patti GJ.: Isotope Tracing in Adult Zebrafish Reveals Alanine Cycling Between Melanoma and Liver. Cell Metabolism, 33(7):1493-1504, 2021. 

     

     

    Selected Awards


     

    Alfred P. Sloan Award, 2014


     

    Pew Biomedical Scholars Award, 2015

     

    Camille Dreyfus Teacher-Scholar Award, 2015

     

    Mallinckrodt Scholar Award, 2016

     

    Inaugural NIEHS award for revolutionizing, innovative, and visionary research, 2017

     

    Blavatnik Award for Young Scientists (National Award Finalist), 2020

     

    ACS Midwest Award, 2023