Gregory S. Ducker

Gregory S. Ducker, PhD

Languages spoken: English

Academic Information

Departments Primary - Biochemistry

Academic Office Information

greg.ducker@biochem.utah.edu

Research Interests

  • Cancer Metabolism
  • Mass Spectrometry
  • Antimetabolites
  • Chemical Biology
  • Mitochondria
  • Tetrahydrofolates

Gregory Ducker is an assistant professor in the Department of Biochemistry. His lab studies mammalian metabolism and its role in diabetes, heart disease and cancer. The lab utilizes mass spectrometry based approaches to quantify molecular reactions in living model systems to understanding the reaction network that support disease processes.

Research Statement

Changes in cellular metabolism underlie many diseases. For example, cancer cells must become proliferative, requiring both increases in the production of key biosynthetic building blocks and new nutrient acquisition strategies to supply them. Research in my group focuses on understanding at a molecular level the fundamental metabolic processes underlying cellular disease physiology- what pathways and processes contribute to disease and how do cells acquire the nutrients to fuel them? One long-term goal of our research is to characterize the metabolic requirements of cancer cells and tumors in vivo in order to identify and validate new therapeutic targets. Our approach is fundamentally biochemical, based on integrating new mass spectrometry technology with CRISPR/Cas9 genetic engineering to be able to precisely quantify metabolic fluxes in vivo. By starting with a fundamentals based perspective on metabolism, we are able to apply our knowledge across different cell types and disease states providing unifying theory to diverse biological presentations.


Education History

Postdoctoral Fellowship Princeton University
 Postdoctoral Fellow
University of California, Berkeley
 PhD
Undergraduate Carleton College
 BA

Selected Publications

Journal Article

  1. Cluntun AA, Badolia R, Lettlova S, Parnell KM, Shankar TS, Diakos NA, Olson KA, Taleb I, Tatum SM, Berg JA, Cunningham CN, Van Ry T, Bott AJ, Krokidi AT, Fogarty S, Skedros S, Swiatek WI, Yu X, Luo B, Merx S, Navankasattusas S, Cox JE, Ducker GS, Holland WL, McKellar SH, Rutter J, Drakos SG (2020). The pyruvate-lactate axis modulates cardiac hypertrophy and heart failure. Cell Metab, 33(3), 629-648.e10.
  2. Panic V, Pearson S, Banks J, Tippetts TS, Velasco-Silva JN, Lee S, Simcox J, Geoghegan G, Bensard CL, van Ry T, Holland WL, Summers SA, Cox J, Ducker GS, Rutter J, Villanueva CJ (2020). Mitochondrial pyruvate carrier is required for optimal brown fat thermogenesis. Elife, 9.
  3. Li AM, Ducker GS, Li Y, Seoane JA, Xiao Y, Melemenidis S, Zhou Y, Liu L, Vanharanta S, Graves EE, Rankin EB, Curtis C, Massague J, Rabinowitz JD, Thompson CB, Ye J (2020). Metabolic Profiling Reveals a Dependency of Human Metastatic Breast Cancer on Mitochondrial Serine and One-Carbon Unit Metabolism. Mol Cancer Res, 18, 599-611.
  4. Bensard CL, Wisidagama DR, Olson KA, Berg JA, Krah NM, Schell JC, Nowinski SM, Fogarty S, Bott AJ, Wei P, Dove KK, Tanner JM, Panic V, Cluntun A, Lettlova S, Earl CS, Namnath DF, Vzquez-Arregun K, Villanueva CJ, Tantin D, Murtaugh LC, Evason KJ, Ducker GS, Thummel CS, Rutter J (2019). Regulation of Tumor Initiation by the Mitochondrial Pyruvate Carrier. Cell Metab, 31(2), 284-300.e7.
  5. Dekhne AS, Shah K, Ducker GS, Katinas JM, Wong-Roushar J, Nayeen MJ, Doshi A, Ning C, Bao X, Frhauf J, Liu J, Wallace-Povirk A, OConnor C, Dzinic SH, White K, Kushner J, Kim S, Httemann M, Polin L, Rabinowitz JD, Li J, Hou Z, Dann CE 3rd, Gangjee A, Matherly LH (2019). Novel Pyrrolo[3,2-d]pyrimidine Compounds Target Mitochondrial and Cytosolic One-carbon Metabolism with Broad-spectrum Antitumor Efficacy. Mol Cancer Ther, 18(10), 1787-1799.
  6. Rodriguez AE, Ducker GS, Billingham LK, Martinez C, Suri V, Friedman A, Manfredi M, Weinberg SE, Rabinowitz JD, Chandel NC (2019). Serine metabolism supports macrophage IL-1β production. Cell Metab, 29(4), 1003-1011.
  7. Rodriguez AE, Ducker GS, Billingham LK, Martinez CA, Mainolfi N, Suri V, Friedman A, Manfredi MG, Weinberg SE, Rabinowitz JD, Chandel NS (2019). Serine Metabolism Supports Macrophage IL-1β Production. Cell Metab, 29(4), 1003-1011.e4.
  8. Dekhne A, Shah K, Ducker GS, Katinas JM, Wong J, Nayeen MJ, Doshi A, Ning C, Bao X, Frhauf J, Wallace-Povirk A, OConnor C, Dzinic S, White K, Kushner J, Kim S, Polin L, Rabinowitz JD, Li J, Hou Z, Dann III CE, Gangjee A, Matherly LM (2019). Novel pyrrolopyrimidine compounds inhibit mitochondrial and cytosolic one-carbon metabolism with broad-spectrum anti-tumor efficacy. . Mol Cancer Ther.
  9. Chamberlain CE, German MS, Yang K, Wang J, VanBrocklin H, Regan M, Shokat KM, Ducker GS, Kim GE, Hann B, Donner DB, Warren RS, Venook AP, Bergsland EK, Lee D, Wang Y, Nakakura EK (2018). A patient-derived xenograft model of pancreatic neuroendocrine tumors identifies sapanisertib as a possible new treatment for everolimus-resistant tumors. Mol Cancer Ther, 17(12), 2702-2709.
  10. Chamberlain CE, German MS, Yang K, Wang J, VanBrocklin H, Regan M, Shokat KM, Ducker GS, Kim GE, Hann B, Donner DB, Warren RS, Venook AP, Bergsland EK, Lee D, Wang Y, Nakakura EK (2018). A Patient-derived Xenograft Model of Pancreatic Neuroendocrine Tumors Identifies Sapanisertib as a Possible New Treatment for Everolimus-resistant Tumors. Mol Cancer Ther, 17(12), 2702-2709.
  11. Rodan LH, Qi W, Ducker GS, Demirbas D, Laine R, Yang E, Walker MA, Eichler F, Rabinowitz JD, Anselm I, Berry GT, Undiagnosed Diseases Network UDN (2018). 5,10-methenyltetrahydrofolate synthetase deficiency causes a neurometabolic disorder associated with microcephaly, epilepsy, and cerebral hypomyelination. Mol Genet Metab, 125(1-2), 118-126.
  12. Rodan L, Qi W, Ducker GS, Demirbas D, Laine R, Yang E, Walker MA, Eichler F, Rabinowitz JD, Anselm I, Berry GT (2018). 5,10-methenyltetrahydrofolate synthetase deficiency causes a neurometabolic disorder associated with microcephaly, epilepsy, and cerebral hypomyelination. Mol Genet Metab.
  13. Morscher RJ, Ducker GS, Li SH, Mayer JA, Gitai Z, Sperl W, Rabinowitz JD (2018). Mitochondrial translation requires folate-dependent tRNA methylation. Nature, 554(7690), 128-132.
  14. Ksionda O, Mues M, Wandler AM, Donker L, Tenhagen M, Jun J, Ducker GS, Matlawska-Wasowska K, Shannon K, Shokat KM, Roose JP (2018). Comprehensive analysis of T cell leukemia signals reveals heterogeneity in the PI3 kinase-Akt pathway and limitations of PI3 kinase inhibitors as monotherapy. PLoS One, 13(5), e0193849.
  15. Ducker GS, Ghergurovich JM, Mainolfi N, Suri V, Jeong SK, Hsin-Jung Li S, Friedman A, Manfredi MG, Gitai Z, Kim H, Rabinowitz JD (2017). Human SHMT inhibitors reveal defective glycine import as a targetable metabolic vulnerability of diffuse large B-cell lymphoma. Proc Natl Acad Sci U S A, 114(43), 11404-11409.
  16. Chen L, Ducker GS, Lu W, Teng X, Rabinowitz JD (2017). An LC-MS chemical derivatization method for the measurement of five different one-carbon states of cellular tetrahydrofolate. Anal Bioanal Chem, 409(25), 5955-5964.
  17. Ducker GS, Chen L, Morscher RJ, Ghergurovich JM, Esposito M, Teng X, Kang Y, Rabinowitz JD (2016). Reversal of Cytosolic One-Carbon Flux Compensates for Loss of the Mitochondrial Folate Pathway. Cell Metab, 23(6), 1140-1153.
  18. Ducker GS, Atreya CE, Simko JP, Hom YK, Matli MR, Benes CH, Hann B, Nakakura EK, Bergsland EK, Donner DB, Settleman J, Shokat KM, Warren RS (2014). Incomplete inhibition of phosphorylation of 4E-BP1 as a mechanism of primary resistance to ATP-competitive mTOR inhibitors. Oncogene, 33(12), 1590-600.
  19. Davies JM, Robinson AE, Cowdrey C, Mummaneni PV, Ducker GS, Shokat KM, Bollen A, Hann B, Phillips JJ (2014). Generation of a patient-derived chordoma xenograft and characterization of the phosphoproteome in a recurrent chordoma. J Neurosurg, 120(2), 331-6.
  20. Pourdehnad M, Truitt ML, Siddiqi IN, Ducker GS, Shokat KM, Ruggero D (2013). Myc and mTOR converge on a common node in protein synthesis control that confers synthetic lethality in Myc-driven cancers. Proc Natl Acad Sci U S A, 110(29), 11988-93.
  21. Atreya CE, Ducker GS, Feldman ME, Bergsland EK, Warren RS, Shokat KM (2012). Combination of ATP-competitive mammalian target of rapamycin inhibitors with standard chemotherapy for colorectal cancer. Invest New Drugs, 30(6), 2219-25.
  22. Wang BT, Ducker GS, Barczak AJ, Barbeau R, Erle DJ, Shokat KM (2011). The mammalian target of rapamycin regulates cholesterol biosynthetic gene expression and exhibits a rapamycin-resistant transcriptional profile. Proc Natl Acad Sci U S A, 108(37), 15201-6.
  23. McCormick SR, McCormick MJ, Grutkoski PS, Ducker GS, Banerji N, Higgins RR, Mendiola JR, Reinartz JJ (2010). FLT3 mutations at diagnosis and relapse in acute myeloid leukemia: cytogenetic and pathologic correlations, including cuplike blast morphology. Arch Pathol Lab Med, 134(8), 1143-51.
  24. Okuzumi T, Ducker GS, Zhang C, Aizenstein B, Hoffman R, Shokat KM (2010). Synthesis and evaluation of indazole based analog sensitive Akt inhibitors. Mol Biosyst, 6(8), 1389-402.

Review

  1. Ducker GS, Rabinowitz JD (2017). One-Carbon Metabolism in Health and Disease. [Review]. Cell Metab, 25(1), 27-42.

Commentary

  1. Ducker GS, Rabinowitz JD (2015). ZMP: a master regulator of one-carbon metabolism. Mol Cell, 57(2), 203-4.

Patent

  1. Rabinowitz JD, Kim H, Ducker GS, Ghergurovich JM (2016). SHMT Inhibitors. U.S. Patent No. PCT/US16/21870. Washington, D.C.:U.S. Patent and Trademark Office.
  2. Rabinowitz JD, Fan J, Ducker GS (2015). NADPH production by the 10-formyl-THF pathway, and its use in the diagnosis and treatment of disease. U.S. Patent No. PCT/US2015/021578. Washington, D.C.:U.S. Patent and Trademark Office.