Research Focus
Lipids, commonly referred to as fat, are a large and diverse group of biomolecules that serve many roles within a cell. Lipids are the major structural component of cellular membranes, the primary means of cellular energy storage, mediators of cell-to-cell communications, and inflammatory factors. Since many lipids exist within the cell as large macromolecules, derived from a combination of smaller metabolic building blocks, it is critical to not only understand the abundance of lipids, but also their structural compositions.
At the CRI, I use my expertise in mass spectrometry and lipid biology to decode the biochemical information stored in lipid macromolecules. This information can be used to broaden our knowledge of lipid maintenance and metabolism in healthy animals and identify potential metabolic liabilities for the treatment of disease. I am specifically interested in how the lipid composition of a cell’s membrane sensitizes it to environmental stressors and prevents the growth and spread of cancer.
About Dr. Mathews
Thomas P. Mathews earned his bachelor’s degree in biochemistry from the University of Virginia and stayed to complete a Ph.D. in bioorganic chemistry. Following his thesis work, Dr. Mathews pursued postdoctoral fellowships at The Scripps Research Institute and Vanderbilt University Medical Center where he studied lipid metabolism and lipid signaling networks. In 2014, Dr. Mathews was awarded a fellowship through Oak Ridge National Laboratory to develop new tests for environmental and industrial toxins at the Centers for Disease Control and Prevention. Dr. Mathews joined the Morrison lab at Children’s Medical Center Research Institute (CRI) at UT Southwestern in 2017 as a senior research scientist focused on the development of mass spectrometry-based metabolomics methods.
In 2020, Dr. Mathews joined the CRI faculty as an assistant professor in research.
Publications
Ubellacker, J.M., Tasdogan, A., Ramesh, V., Shen, B., Mitchell, E.C. Martin, M., Gu, Z., McCormick, M.L., Durham, A.B., Spitz, D.R., Zhao, Z., Mathews, T.P., Morrison, S.J. (2020) Lymph protects metastasizing melanoma cells from ferroptosis Nature 585, 113-118. (PubMed)
DeVilbiss, A.W., Zhao, Z., Martin-Sandoval, M.S., Ubellacker, J.M., Tasdogan, A., Agathocleous, M., Mathews, T.P.,‡ Morrison, S.J. (2020) Metabolomic profiling of rare cell populations isolated by flow cytometry from tissues bioRxiv doi: 10.1101/2020.08.11.246900.
Tasdogan, A., Faubert, B., Ramesh, V., Ubellacker, J.M., Shen, B., Solmonson, A., Murphy, M.M., Gu, Z., Gu, W., Martin, M., Kasitinon, S.Y., Vandergriff, T., Mathews, T.P., Zhao, Z., Schadendorf, D., DeBerardinis, R.J., Morrison, S.J. (2020) Metabolic heterogeneity confers differences in melanoma metastatic potential Nature 577, 115-120. (PubMed)
Luengo, A., Abbott, K.L., Davidson, S.M., Hosios, A.M., Faubert, B., Chan, S.H., Freinkman, E., Zacharias, L.G., Mathews, T.P., Clish, C.B., DeBerardinis, R.J., Lewis, C.A., Vander Heiden, M.G. (2019) Reactive metabolite production is a targetable liability of glycolytic metabolism in lung cancer Nature Communications 10 5604. (PubMed)
Kasitinon, S.Y., Eskiocak, U., Martin, M., Bezwada, D., Khivansara, V., Tasdogan, A., Zhao, Z., Mathews, T.P., Aurora, A.B., Morrison, S.J. (2020) TRPML1 promotes protein homeostasis in melanoma cells by negatively regulating AMPK and mTORC1 signaling Cell Reports 9 2293-2305. (PubMed)
Sanford, A.A., Isenberg, S.L, Carter, M.D., Mojica, M.A., Mathews, T.P., Harden, L.A., Takeoka, G.R., Thomas, J.D., Pirkle, J.L., Johnson, R.C. (2018) Quantitative HPLC-MS/MS Analysis of Toxins in Soapberry Seeds: Methylenecyclopropylglycine and Hypoglycin A Food Chemistry 264, 449-454. (PubMed)
Sanford, A.A., Isenberg, S.L., Carter, M.D., Mojica, M.A., Mathews T.P., Laughlin, S., Thomas, J.D., Pirkle, J.L., Johnson, R.C. (2018) Quantification of Hypoglycin A and Methylenecyclopropylglycine in Human Plasma by HPLC-MS/MS J. Chrom. B 1095, 112-118. (PubMed)
Mathews, T.P., Carter, M.D., Johnson, D., Isenberg, S.L., Graham, L.A., Thomas, J.D., Johnson, R.C. (2017) High Confidence Qualitative Identification of Organophosphorus Nerve Agent Adducts to Human Butyrylcholinesterase Anal. Chem. 89, 1955-1964. (PubMed)
Shrivastava, A., Kumar, A., Thomas, J.D., Laserson, K.F., Bhushan, G., Carter, M.D., Chhabra, M., Mittal, V., Khare, S., Sejvar, J.J., Dwivedi, M., Isenberg, S.L., Johnson, R.C., Pirkle, J.L., Sharer, J.D., Hall, P.L., Yadav, R., Velayudhan, A., Papanna, M., Singh, P., Somashekar, D., Pradhan, A., Goel, K., Pandey, R., Kumar, M., Kumar, S., Chakrabarti, A., Sivaperumal, P., Kumar, A.R., Schier, J.G., Chang, A., Graham, L.A., Mathews, T.P., Johnson, D., Valentin, L., Caldwell, K.L., Jarrett, J.M., Harden, L.A., Takeoka, G.R., Tong, S., Queen, K., Paden, C., Whitney, A., Haberling, D.L., Singh, R., Singh, R.S., Earhart, K.C., Dhariwal, A.C., Chauhan, L.S., Venkatesh, S., Srikantiah, P. (2017) Association of Acute Toxic Encephalopathy with Litchi Consumption in an Outbreak in Muzaffarpur, India, 2014: A Case-Control Study Lancet Global Health 5, e458-e466. (PubMed)
Graham, L.A., Johnson, D., Carter, M.D., Stout, E.G., Erol, H.A., Isenberg, S.L., Mathews, T.P., Thomas, J.D., Johnson, R.C. (2016) A high-throughput UHPLC–MS/MS method for the quantification of five aged butyrylcholinesterase biomarkers from human exposure to organophosphorus nerve agents Biomed. Chromatogr. DOI: 10.1002/bmc.3830. (PubMed)
Isenberg, S.L., Carter, M.D., Hayes, S.R., Graham, L.A., Johnson, D., Mathews, T.P., Harden, L.A., Takeoka, G.R., Thomas, J.D., Pirkle, J.L., Johnson, R.C. (2016) Quantification of Toxins in Soapberry (Sapindaceae) Arils: Hypoglycin A and Methylenecyclopropylglycine J. Agric. Food Chem. 64, (27) 5607-561. (PubMed)
Mathews, T.P., Hill, S., Rose, K.L., Ivanova, P.T., Lindsley, C.W., Brown, H.A. (2015) Human Phospholipase D Activity Transiently Regulates Pyrimidine Biosynthesis in Malignant Gliomas ACS Chem. Biol. 10, 1258-1268. (PubMed)
Isenberg, S.L., Carter, M.D., Graham, L.A., Mathews, T.P., Johnson, D., Thomas, J.D., Pirkle, J.L., Johnson, R.C. (2015) Quantification of Metabolites for Assessing Human Exposure to Soapberry Toxins Hypoglycin A and Methylenecyclopropylglycine Chem. Res. Toxicol. 28, 1753-1759. (PubMed)
Taylor, H.E., Simmons, G.E., Mathews, T.P., Khatua, A.K., Popik, W., Lindsley, C.W., D’Aquila, R.T., Brown, H.A. (2015) Phospholipase D1 Couples CD4+ T Cell Activation to c-Myc-Dependent Deoxyribonucleotide Pool Expansion and HIV-1 Replication PLOS Pathogens DOI: 10.1371/journal.ppat.1004864. (PubMed)
Gorden, D.L., Myers, D.S., Ivanova, P.T., Fahy, E., Maurya, M.R., Gupta, S., Min, J., Spann, N.J., McDonald, J.G., Kelly, S.L., Duan, J., Sullards, M.C., Leiker, T.J., Barkley, R.M., Quehenberger, O., Armando, A.M., Milne, S.B., Mathews, T.P., Armstrong, M.D., Li, C., Melvin, W.V., Clements, R.H., Washington, M.K., Mendonsa, A.M., Wiztum, J.L., Guan, Z., Glass, C.K., Murphy, R.C., Dennis, E.A., Merrill, Jr. A.H., Russell, D.W., Subramaniam, S., Brown, H.A., (2015) Biomarkers of NAFLD progression – an omics approach to an epidemic J. Lipid Res. 56, 722-736. (PubMed)
Scott, S.A., Mathews, T.P.,** Ivanova, P.T., Brown, H.A., (2014) Chemical modulation of glycerolipid signaling and metabolic pathways Biochem. Biophys. Acta. Mol Cell Biol Lipids. 1841, 1060-1084. (PubMed)
Wenthur, C.J., Gentry, P.R., Mathews, T.P., Lindsley, C.W. (2014) Drugs for Allosteric Sites on Receptors Ann. Rev. Pharm. Tox. 54, 165‐184. (PubMed)
Scott, S.A., Xiang, Y., Mathews, T.P., Plumley, H.C., Myers, D.S., Armstrong, M.D., Tallman, K.A., O’Reilly, M.C., Lindsley, C.W., Brown, H.A., (2013) Regulation of Phospholipase D Activity and Phosphatidic Acid Production Following Purinergic (P2Y6) Receptor Stimulation J. Biol. Chem. 288, 20477‐ 20487. (PubMed)
Milne, S.B., Mathews, T.P., Myers, D.S., Ivanova, P.T., Brown, H.A., (2013) Sum of the Parts: Mass Spectrometry‐Based Metabolomics Biochemistry 52, 3829-3840. (PubMed)
Kharel, Y., Mathews, T.P.,** Gellett, A.M., Tomsig, J.L., Kennedy, P.C., Moyer, M.L., Macdonald, T.L., Lynch, K.R., (2011) Sphingosine kinase type 1 inhibition reveals rapid turnover of circulating sphingosine 1-phosphate Biochem. J. 440 345-353. (PubMed)
Kennedy, A.J., Mathews, T.P., Kharel, Y., Field, S.D., Moyer, M.L., East, J.E., Houck, J.D., Lynch, K.R., Macdonald, T.L. (2011) Development of amidine‐based sphingosine kinase 1 nanomolar inhibitors and reduction of sphingosine 1-phosphate in human leukemia cells J. Med. Chem. 54, 3524-3548. (PubMed)
Kennedy, P.C., Zhu, R., Huang, T., Tomsig, J.L., Mathews, T.P., David, M., Peyruchaud, O., Macdonald, T.L., Lynch, K.R. (2011) Characterization of a Sphingosine 1-Phosphate Receptor Antagonist Prodrug J. Pharmacol. Exp. Ther. 338, 879-889. (PubMed)
Kharel, Y., Mathews, T.P., Kennedy, A.J., Houck, J.D., Macdonald, T.L., Lynch, K.R. (2011) A Rapid Assay for Sphingosine Kinase Activity Anal. Biochem. 411, 230-235. (PubMed)
Mathews, T.P., Kennedy, A.J., Kharel, Y., Kennedy, P.C., Nicoara, O., Sunkara, M., Morris, A.J., Wamhoff, B., Lynch, K.R., Macdonald, T.L., (2010) Discovery, Biological Evaluation and the Structure-Activity Relationship of Amidine‐based Sphingosine Kinase Inhibitors J. Med. Chem. 53, 2766-2778. (PubMed)
Foss, F.W., Mathews, T.P.,** Kharel, Y., Kennedy, P.C., Snyder, A.H., Davis, M.D., Lynch, K.R., Macdonald, T.L. (2009) Synthesis and Biological Evaluation of Sphingosine Kinase Substrates as Sphingosine-1-Phosphate Receptor Prodrugs Bioorg. Med. Chem. 17, 6123-6136. (PubMed)
** = co-first authorship
‡ = co-corresponding authorship
