Gregory S. Ducker, PhD

Research Interests

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

Labs

Lab Website

Languages

  • English

Academic Information

  • Departments: Biochemistry - Assistant Professor

Academic Office Information

  • 801-213-1236
  • Emma Eccles Jones Medical Research Building
    15 N Medical Dr E, Room: 5520N
    Salt Lake City, UT

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

Type School Degree
Postdoctoral Fellowship Princeton University
Cancer Metabolism
Postdoctoral Fellow
Doctoral Training University of California, Berkeley
Chemistry
Ph.D.
Undergraduate Carleton College
Chemistry with honors; Minor: Political Economy
B.A.

Selected Publications

Journal Article

  1. 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. (Epub ahead of print) Mol Cancer Res.
  2. 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. (Epub ahead of print) Cell Metab.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.

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.