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RESEARCH AREAS

SPECIFIC INTERRELATED AREAS

  • The Serine, Glycine, One Carbon (SGOC) Network

  • Methionine metabolism  

  • Glucose Metabolism and the Warburg Effect

  • Central Carbon Metabolism and Mitochondrial Biology 

  • Targeting Metabolism for Cancer Therapy and Prevention

  • Mass Spectrometry and Bioinformatics Technology 

  • Computational Approaches for Understanding Metabolic Networks and Regulation

  • Modeling Gene-Environment Interactions in Metabolism

  • Immunometabolism

ONE CARBON METABOLISM, THE METHIONINE CYCLE, AND HISTONE METHYLATION

Recent work has described a mechanism whereby the regulation of methionine metabolism affects methylation status in cells.  This regulation occurs through S-adenosylmethionine and its ability to potentiate methylation rreactions.  We have recently shown that Histone methylation is dramatically affected by changes in flux in the methionine cycle.  We are further investigating this phenomena.   

MASS SPECTROMETRY FOR QUANTITATIVE METABOLIC SIGNALING FLUX

We are using quantitative metabolomics approaches to measure to measure the methionine cycle flux under conditions of altered nutrient status.  These perturbations include differences in vitamins, amino acids, and glucose in controlled settings.  For each of these experiments stable isotope tracers will be considered and fluxes through methylation metabolism will be measured.  In addition the levels of metabolites in the methionine cycle will also be measured.    

DIRECT MEASUREMENTS OF SIGNALING FLUX FROM METABOLISM TO THE CHROMATIN

We will then connect the measured metabolite concentrations to signaling flux.  We will first measurement using quantitative western blotting of key modifications.  We will match the conditions under which we considered quantitative metabolomics and consider the state of histone modifications in these conditions.  To confirm the connections, we will measure and quantify the kinetics of signaling flux using isotopically labeled substrates.  Ultimately we will investigate the cancer context of this understudied form of cellular regulation. 

DR. JASON LOCASALE

Dr. Locasale completed his B.A. in Chemistry from Rutgers, his PhD in Biological Engineering from MIT, and his postdoc at Harvard Medical School. He was a professor at Cornell University before joining the Department of Pharmacology and Cancer Biology at Duke University. He is widely regarded as a leader in the field of metabolic research, with a focus on cancer metabolism.

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Locasale Lab - Duke University School of Medicine 

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