JASON LOCASALE, PH.D.

Locasale Assistant Professor of Pharmacology and Cancer Biology

Duke University School of Medicine
C270A LSRC
Box 3813
Durham, NC 27710

Phone: 919-684-9309
E-mail: Jason [Dot] Locasale [At] duke [Dot] edu
Website

Research Interests

We are interested in developing and applying advanced methodologies to understand metabolism and its contribution to health disease. In doing so, we hope to gain deeper mechanistic insight and define the precise contexts for which targeting metabolism for cancer therapy and metabolic health may be effective. We also seek to learn more about the basic regulatory networks of metabolism and how metabolism interacts with chromatin biology. Our approach is a multidisciplinary one where we develop and apply leading metabolomics approaches rooted in analytical chemistry and computational biology to probe cellular metabolism. These tools are combined with rigorous experimentation using biochemistry and genetics on model systems and population studies using data from human patients.

A current list of publications is found at: http://www.ncbi.nlm.nih.gov/pubmed/?term=locasale+j

Representative Publications

McDonald OG, Li X, Saunders T, Tryggvadottir R, Mentch SJ, Warmoes MO, Word AE, Carrer A, Salz TH, Natsume S, Stauffer KM, Makohon-Moore A, Zhong Y, Wu H, Wellen KE, Locasale JW, Iacobuzio-Donahue CA, Feinberg AP. Epigenomic reprogramming during pancreatic cancer progression links anabolic glucose metabolism to distant metastasis. Nature Genetics. 2017. doi: 10.1038/ng.3753. PubMed PMID: 28092686.

Wang Q, Liberti MV, Liu P, Deng X, Liu Y, Locasale JW, Lai L. Rational Design of Selective Allosteric Inhibitors of PHGDH and Serine Synthesis with Anti-tumor Activity. Cell Chemical Biology. 2016. doi: 10.1016/j.chembiol.2016.11.013. PubMed PMID: 28042046.

Ser Z, Gao X, Johnson C, Mehrmohamadi M, Liu X, Li S, Locasale JW. Targeting One Carbon Metabolism with an Antimetabolite Disrupts Pyrimidine Homeostasis and Induces Nucleotide Overflow. Cell Reports. 2016;15(11):2367-76. doi: 10.1016/j.celrep.2016.05.035. PubMed PMID: 27264180; PMCID: PMC4909568.

Pan M, Reid MA, Lowman XH, Kulkarni RP, Tran TQ, Liu X, Yang Y, Hernandez-Davies JE, Rosales KK, Li H, Hugo W, Song C, Xu X, Schones DE, Ann DK, Gradinaru V, Lo RS, Locasale JW, Kong M. Regional glutamine deficiency in tumours promotes dedifferentiation through inhibition of histone demethylation. Nature Cell Biology. 2016;18(10):1090-101. doi: 10.1038/ncb3410. PubMed PMID: 27617932.

Mehrmohamadi M, Mentch LK, Clark AG, Locasale JW. Integrative modelling of tumour DNA methylation quantifies the contribution of metabolism. Nature Communications. 2016;7:13666. doi: 10.1038/ncomms13666. PubMed PMID: 27966532; PMCID: PMC5171841.

Liu X, Romero IL, Litchfield LM, Lengyel E, Locasale JW. Metformin Targets Central Carbon Metabolism and Reveals Mitochondrial Requirements in Human Cancers. Cell Metabolism. 2016;24(5):728-39. doi: 10.1016/j.cmet.2016.09.005. PubMed PMID: 27746051.

Dai Z, Shestov AA, Lai L, Locasale JW. A Flux Balance of Glucose Metabolism Clarifies the Requirements of the Warburg Effect. Biophysical Journal. 2016;111(5):1088-100. doi: 10.1016/j.bpj.2016.07.028. PubMed PMID: 27602736; PMCID: PMC5018130.

Dai Z, Locasale JW. Understanding metabolism with flux analysis: From theory to application. Metabolic Engineering. 2016. doi: 10.1016/j.ymben.2016.09.005. PubMed PMID: 27667771.

Liberti MV, Locasale JW. The Warburg Effect: How Does it Benefit Cancer Cells? Trends in Biochemical Sciences. 2016;41(3):211-8. doi: 10.1016/j.tibs.2015.12.001. PubMed PMID: 26778478; PMCID: PMC4783224.

Mentch SJ, Mehrmohamadi M, Huang L, Liu X, Gupta D, Mattocks D, Gomez Padilla P, Ables G, Bamman MM, Thalacker-Mercer AE, Nichenametla SN, Locasale JW. Histone Methylation Dynamics and Gene Regulation Occur through the Sensing of One-Carbon Metabolism. Cell Metabolism. 2015;22(5):861-73. doi: 10.1016/j.cmet.2015.08.024. PubMed PMID: 26411344; PMCID: PMC4635069.

Cluntun AA, Huang H, Dai L, Liu X, Zhao Y, Locasale JW. The rate of glycolysis quantitatively mediates specific histone acetylation sites. Cancer and Metabolism. 2015;3:10. doi: 10.1186/s40170-015-0135-3. PubMed PMID: 26401273; PMCID: PMC4579576.

Mehrmohamadi M, Liu X, Shestov AA, Locasale JW. Characterization of the usage of the serine metabolic network in human cancer. Cell Reports. 2014;9(4):1507-19. doi: 10.1016/j.celrep.2014.10.026. PubMed PMID: 25456139; PMCID: PMC4317399.

Shestov AA, Liu X, Ser Z, Cluntun AA, Hung YP, Huang L, Kim D, Le A, Yellen G, Albeck JG, Locasale JW. Quantitative determinants of aerobic glycolysis identify flux through the enzyme GAPDH as a limiting step. Elife. 2014;3. doi: 10.7554/eLife.03342. PubMed PMID: 25009227; PMCID: PMC4118620.

Liu X, Ser Z, Locasale JW. Development and quantitative evaluation of a high-resolution metabolomics technology. Analytical Chemistry. 2014;86(4):2175-84. doi: 10.1021/ac403845u. PubMed PMID: 24410464; PMCID: PMC3983012.


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