Portrait Douglas Spitz
Professor
douglas-spitz@uiowa.edu
Phone: 
(319) 335-8001
Office: 
Director - Free Radical Radiation Biology Program Professor of Radiation Oncology Holden Comprehensive Cancer Center B180 Medical Laboratories The University of Iowa Iowa City, Iowa 52242 Fax:319-335-8039
Person Type: 
Primary Faculty
Résumé/Curriculum Vitae: 
PDF icon spitz_cv_6-17-22.pdf

Research Statement

Dr. Spitz is a well-established investigator whose laboratory has made many significant contributions to the field of oxidative stress in cancer biology and toxicology. His laboratory was the first to discover that chronic exposure of mammalian cells to O2•- and H2O2 was capable of inducing genomic instability and gene amplification that resulted in a large increases in cellular resistance to oxidative stress associated with cancer therapy. His laboratory was also the first to discover that glucose deprivation preferentially killed cancer vs. normal cells by metabolic oxidative stress mediated by mitochondrial O2•-and H2O2. In this work his lab also showed that tumor cell mitochondria were producing much greater levels of O2•- and H2O2, relative to normal cells and this apparent defect in cancer cell mitochondrial metabolism could be exploited for therapeutic purposes. This work continues to have a significant impact on the field of cancer biology and therapy and Dr. Spitz’s group has received R21 support from the NCI to initiate clinical trials using ketogenic diets to enhance cancer therapy based on these basic science observations as well as having funded and pending grant applications using these principles to improve cancer therapy outcomes using redox active small molecules.

His laboratory has also been involved with collaborative studies leading to the discovery of the role of oxidized CaMKII in cardiovascular disease. He has also collaborated on the discovery of the role that Sirt3 plays in maintenance of mitochondrial oxidative metabolism during stress leading to malignant transformation and the fact that MnSOD is a target for Sirt3 activation during ionizing radiation-induced injury relevant to transformation and normal tissue damage during radiotherapy.

Dr. Spitz is also a well-established mentor for trainees and junior faculty studying Redox Biology and Medicine. He serves as the director of the Free Radical and Radiation Biology Graduate Program at the University of Iowa as well as the director of the Free Radical Metabolism and Imaging Program and the Radiation and Free Radical Research Core Laboratory in the Holden Comprehensive Cancer Center. He is the PI of an NCI funded T32 Training Program in Free Radical and Radiation Biology, as well as NCI K, F, RO1 and R21 grants.

Example Publications

(Complete listing on  Google Scholar and National Library of Medicine)

  1. Spitz DR and Oberley LW:  An assay for superoxide dismutase activity in mammalian tissue homogenates.  Anal. Biochem. 1989; 179:8-18.  PMID: 2547324
  2. Hunt CR, Sim JE, Featherstone T, Golden W, Von Kapp-Herr C, Hock RA, Gomez RA, Parsian AJ, and Spitz DR: Genomic instability and catalase gene amplification induced by chronic exposure to oxidative stress. Cancer Res. 1998; 58:3986-3992. PMID: 9731512
  3. Spitz DR, Sim JE, Ridnour LA, Galoforo SS, and Lee YJ: Glucose deprivation-induced oxidative stress in human tumor cells: a fundamental defect in metabolism? Ann. NY Acad. Sci. 2000; 899:349-362. PMID: 10863552
  4. Spitz DR, Azzam EI, Li JJ, and Gius D: Metabolic oxidation/reduction reactions and cellular responses to ionizing radiation: a unifying concept in stress response biology. Cancer and Metastasis Reviews 2004; 23:311–322. PMID: 15197331
  5. Ahmad IM, Aykin-Burns N, Sim JE, Walsh SA, Higashikubo R, Buettner GR, Venkataraman S, Mackey MA, Flanagan S, Oberley LW, and Spitz DR: Mitochondrial O2•- and H2O2 mediate glucose deprivation-induced cytotoxicity and oxidative stress in human cancer cells. J. Biol. Chem. 2005; 280(6):4254-4263. PMID: 15561720
  6. Slane BG, Aykin-Burns N, Smith BJ, Kalen AL, Goswami PC, Domann FE, and Spitz DR: Mutation of succinate dehydrogenase subunit C (SDHC) results in increased O2•-, oxidative stress, and genomic instability. Cancer Res. 2006; 66(15):7615-7620. PMID: 16885361
  7. Erickson JR, Joiner ML, Guan X, Kutschke W, Yang J, Oddis CV, Bartlett RK, Lowe JS, O'Donnell SE, Aykin-Burns N, Zimmerman MC, Zimmerman K, Ham AJ, Weiss RM, Spitz DR, Shea MA, Colbran RJ, Mohler PJ, and Anderson ME. A dynamic pathway for calcium-independent activation of CaMKII by methionine oxidation. Cell. 2008; 133(3):462-474. PMID: 18455987 PMCID: PMC2435269
  8. Aykin-Burns N, Ahmad IM, Zhu Y, Oberley L, and Spitz DR. Increased levels of superoxide and hydrogen peroxide mediate the differential susceptibility of cancer cells vs. normal cells to glucose deprivation. Biochem J. 2009; 418:29-37. PMID: 18937644  PMCID: PMC2678564
  9. Tao R, Coleman MC, Pennington D, Ozden O, Park S-H, Jiang H, Kim H-S, Flynn CR, Hill S, McDonald WH, Olivier AK, Spitz DR, and Gius D: Sirt3-mediated deacetylation of evolutionarily conserved lysine 122 regulates MnSOD activity in response to stress. Mol. Cell 2010; 40(6):893-904. PMID: 21172655 PMCID: PMC3266626
  10. Schoenfeld JD, Sibenaller ZA, Mapuskar KA, Wagner BA, Cramer-Morales KL, Furqan M, Sandhu S, Carlisle TL, Smith MC, Abu Hejleh T, Berg DJ, Zhang J, Keech J, Parekh KR, Bhatia S, Monga V, Bodeker KL, Ahmann L, Vollstedt S, Brown H, Shanahan Kauffman EP, Schall ME, Hohl RJ, Clamon GH, Greenlee JD, Howard MA, Schultz MK, Smith BJ, Riley DP, Domann FE, Cullen JJ, Buettner GR, Buatti JM, Spitz DR*, Allen BG*: (2017) O2·- and H2O2-mediated disruption of Fe metabolism causes the differential susceptibility of NSCLC and GBM cancer cells to pharmacological ascorbate. Cancer Cell. 31(4):487-500.e8  PMID: 28366679  http://dx.doi.org/10.1016/j.ccell.2017.02.018 NIHMS ID: NIHMS857911 (*co-corresponding authors).
  11. Luo M, Shang L, Brooks MD, Jiagge E, Zhu Y, Buschhaus JM, Conley S, Fath MA, Davis A, Gheordunescu E, Wang Y, Harouaka R, Lozier A, Triner D, McDermott S, Merajver SD, Luker GD, Spitz DR, Wicha MS. Targeting Breast Cancer Stem Cell State Equilibrium through Modulation of Redox Signaling. Cell Metab. 2018; 28(1):69-86.e6. doi: 10.1016/j.cmet.2018.06.006. PMID: 29972798
  12. Spitz DR: Manipulations of Redox Metabolism for Enhancing Radiation Therapy Responses: A historical perspective and new hypothesis. Semin Radiat Oncol. 2019; 29(1):1-5. PMID: 30573179.
  13. Spitz DR, Buettner GR, Petronek MS, St-Aubin JJ, Flynn RT, Waldron TJ, Limoli CL. An integrated physico-chemical approach for explaining the differential impact of FLASH versus conventional dose rate irradiation on cancer and normal tissue responses. Radiother Oncol. 2019; pii: S0167-8140(19)30150-1. doi: 10.1016/j.radonc.2019.03.028. [Epub ahead of print] PMID: 31010709
  14. Allen BG, Bodeker KL, Smith MC, Monga V, Sandhu S, Hohl R, Carlisle T, Brown H, Hollenbeck N, Vollstedt S, Greenlee JD, Howard MA, Mapuskar KA, Seyedin SN, Caster JM, Jones KA, Cullen JJ, Berg D, Wagner BA, Buettner GR, TenNapel MJ, Smith BJ, Spitz DR, Buatti JM. First-in-Human Phase I Clinical Trial of Pharmacologic Ascorbate Combined with Radiation and Temozolomide for Newly Diagnosed Glioblastoma. Clin Cancer Res. 2019; 25(22):6590-6597. doi: 10.1158/1078-0432.CCR-19-0594. PMID: 31427282
  15. Falls-Hubert KC, Butler AL, Gui K, Anderson M, Li M, Stolwijk JM, Rodman SN, Solst SR, Tomanek-Chalkley A, Searby CC, Sheffield VC, Sandfort V, Schmidt H, McCormick ML, Wels BR, Allen BG, Buettner GR, Schultz MK, Spitz DR: Disulfiram causes selective hypoxic cancer cell toxicity and radio-chemo-sensitization via redox cycling of copper. Free Radic Biol Med 2020; 150:1-11. PMID: 32032663
  16. Ubellacker JM, Tasdogan A, Ramesh V, Shen B, Mitchell EC, Martin-Sandoval MS, Gu Z, McCormick ML, Durham AB, Spitz DR, Zhao Z, Mathews TP, Morrison SJ. Lymph protects metastasizing melanoma cells from ferroptosis. Nature 2020; 585(7823):113-118. doi: 10.1038/s41586-020-2623-z. PMID: 32814895
  17. Carter CS, Huang SC, Searby CC, Cassaidy B, Zhang Q, Miller MJ, Grzesik WJ, Bradberry K, Pak TK, Walsh S, Dick DW, Akurathi V, Acevedo M, Piorczynski TB, Mapuskar KA, Milne G, Hinton A, Guo D-F, Falls-Hubert KC, Wagner BA, Carter WA, Norris AW, Rahmouni K, Buettner GR, Hansen J, Spitz DR, Abel ED, Sheffield VC: Electromagnetic fields modulate the systemic redox state to treat type 2 diabetes. Cell Metab. 2020; 32(4):561-574.e7. doi: 10.1016/j.cmet.2020.09.012. PMID: 33027675
  18. Sishc BJ, Ding L, Nam T-K, Heer CD, Rodman SN, Schoenfeld JD, Fath MA, Saha D, Pulliam CF, Beardsley RA, Riley DP, Keene JL, Spitz DR* and Story MD*. Avasopasm manganese acts synergistically with ablative hypo-fractionated radiation through the generation of hydrogen peroxide. Science Translational Medicine 2021; 2:13(593):eabb3768. doi: 10.1126/scitranslmed.abb3768. PMID: 33980575. (*co-corresponding authors)
  19. Furqan M, Abu-Hejleha T, Stephens LM, Hartwig SM, Mott SL, Pulliam CF, Petronek M, Heinrich JB, Fath MA, Houtman JCD, Varga SM, Bodeker KL, Bossler AD, Bellizzi AM, Zhang J, Monga V, Mania H, Ivanovic M, Smith BJ, Byrne MM, Wagner BA, Buettner GR, Cullen JJ, Buatti JM, Spitz DR, Allen BG: Pharmacological Ascorbate Improves the Response to Platinum-based Chemotherapy in Advanced Stage Non-Small Cell Lung Cancer: A Phase II Non-Randomized Clinical Trial. Redox Biol 2022; 53:102318. PMID: 35525024

Honors, Awards and Organizations

  • 2020-present    Editorial Board Member – Antioxidants
  • 2019-present    Fellow - Society for Redox Biology and Medicine
  • 2015-present    CSR/NCI ZCA1 GRB-S M1 S, Outstanding Investigator Award Study Section (ad hoc reviewer)
  • 2014-2019    CSR/NCI Tumor Cell Biology (TCB) (standing member)
  • 2013-present     Editorial Board Member – Cancer Research
  • 2013-present    Editorial Board Member – Radiation Research
  • 2010-2011, 2017    NCI F, F30-32 NRSA Fellowship Award review panel
  • 2012, 2020    NCI-F, K Award Career Development Review Panel
  • 2000-present    Editorial Board Member – Free Radical Biology and Medicine
  • 1995, 2005, 2006-2010    CSR/NCI Radiation Therapeutics and Biology (RTB) (standing member)
  • 1995, 2002    NIH Toxicology-I Study Section (ad hoc reviewer)
  • 1990    Young Investigator Award - International Society for Free Radical Research/Oxygen Society

Education

  • PhD, 1984, Radiation Biology, Minor-Biochemistry, University of Iowa, Iowa City, Iowa
  • B.A., Biology/Sociology, 1978, Grinnell College, Grinnell, Iowa