Douglas Spitz
Professor
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: 
Résumé/Curriculum Vitae: 

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

  •  Simons AL, Ahmad IM, Mattson DM, Dornfeld KJ, and Spitz DR: 2-Deoxy-D-glucose (2DG) combined with cisplatin enhances cytotoxicity via metabolic oxidative stress in human head and neck cancer cells. Cancer Res. 2007; 67(7): 3364–70. PMID: 17409446
  •  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. PMCID:PMC2435269.
  •  Aykin-Burns N, Ahmad IM, Zhu Y, Oberley LW, 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. PMCID:PMC2678564
  • Kim H-S, Patel K, Muldoon-Jacobs K, Bisht KS, Aykin-Burns N, Pennington JD, van der Meer R, Nguyen P, Savage J, Owens KM, Vassilopoulos A, Ozden O, Park S-H, Singh KK, Abdulkadir SA, Spitz DR, Deng C-X, and Gius D: SIRT3 is a mitochondrial localized tumor suppressor required for maintenance of mitochondrial integrity and metabolism during stress. Cancer Cell 2010; 17:41–52. PMCID:PMC3711519.
  •  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. PMCID:PMC3266626.
  •  He BJ, Joiner MA, Kutschke W, Yang J, Guan X, Spitz DR, Weiss R, Mohler PJ and Anderson ME: Oxidation of CaMKII determines cardiotoxic effects of aldosterone. Nat Med 2011; 17:1610-8. PMCID:PMC3332099.
  • Orcutt KP, Parsons AD, Sibenaller ZA, Scarbrough PM, Zhu Y, Sobhakumari A, Wilke WW, Kalen AL, Goswami PC, Miller FJ Jr, Spitz DR, and Simons AL: Erlotinib-mediated inhibition of EGFR signaling induces metabolic oxidative stress through NOX4. Cancer Res. 2011; 71(11):3932-40. PMCID:PMC3217301.
  • Fath MA, Ahmad IM, Smith CJ, Spence JM, Spitz DR: Enhancement of carboplatin-mediated lung cancer cell killing by simultaneous disruption of glutathione and thioredoxin metabolism. Clin Cancer Res. 2011; 17(19):6206-17. PMCID:PMC3186854.
  • Owens KM, Aykin-Burns N, Dayal D, Coleman MC, Domann FE, and Spitz DR: Genomic instability induced by mutant succinate dehydrogenase subunit D (SDHD) is mediated by O2-• and H2O2. Free Radic Biol Med. 2012; 52(1):160-6. PMCID: PMC3249516.
  • Scarbrough PM, Mattson DM, Gius D, Watson WH, and Spitz DR: Simultaneous inhibition of glutathione- and thioredoxin-dependent metabolism is necessary to potentiate 17AAG-induced cancer cell killing via oxidative stress. Free Radic Biol Med. 2012; 52(2):436-43. PMCID:PMC3664944.
  • Bey EA, Reinicke KE, Srougi MC, Varnes M, Anderson VE, Pink JJ, Li LS, Patel M, Cao L, Moore Z, Rommel A, Boatman M, Lewis C, Euhus DM, Bornmann WG, Buchsbaum DJ, Spitz DR, Gao J, Boothman DA: Catalase abrogates β-lapachone-induced PARP1 hyperactivation-directed programmed necrosis in NQO1-positive breast cancers. Mol Cancer Ther. 2013; 12(10):2110-20. PMID:23883585
  • Allen BG, Bhatia SK, Buatti JM, Brandt KE, Lindholm KE, Button AM, Szweda LI, Smith BJ, Spitz DR*, Fath MA*: Ketogenic diets enhance oxidative stress and radio-chemo-therapy responses in lung cancer xenografts. Clin Cancer Res. 2013; 19(14):3905-13. PMID:23743570 (*co-corresponding authors)
  • Coleman MC, Olivier AK, Jacobus JA, Mapuskar KA, Mao G, Martin SM, Riley DP, Gius D, Spitz DR: Superoxide Mediates Acute Liver Injury in Irradiated Mice Lacking Sirtuin 3. Antioxid Redox Signal. 2014; 20(9):1423-35.  PMID:23919724
  • Li L, Fath MA, Scarbrough PM, Watson WH, and Spitz DR: Combined inhibition of glycolysis, the pentose cycle, and thioredoxin metabolism selectively increases cytotoxicity and oxidative stress in human breast and prostate cancer Redox. Biol. 2015; 4:127-35. doi: 10.1016/j.redox.2014.12.001. PMID: 25560241
  • Du J, Cieslak JA 3rd, Welsh JL, Sibenaller ZA, Allen BG, Wagner BA, Kalen AL, Doskey CM, Strother RK, Button AM, Mott SL, Smith B, Tsai S, Mezhir J, Goswami PC, Spitz DR, Buettner GR, Cullen JJ: Pharmacological ascorbate radiosensitizes pancreatic cancer. Cancer Res. 2015; 75(16):3314-26. doi: 10.1158/0008-5472.CAN-14-1707. PMID: 26081808
  • Rodman SN, Spence JM, Ronnfeldt TJ, Zhu Y, Solst SR, O'Neill RA, Allen BG, Guan X, Spitz DR, Fath MA. Enhancement of radiation response in breast cancer stem cells by inhibition of thioredoxin- and glutathione-dependent metabolism. Radiat Res. 2016; 186(4):385-395. PMID: 27643875.
  • 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).
  • Sciegienka SJ, Solst SR, Falls KC, Schoenfeld JD, Klinger AR, Ross NL, Rodman SN, Spitz DR, Fath MA: D-penicillamine combined with inhibitors of hydroperoxide metabolism enhances lung and breast cancer cell responses to radiation and carboplatin via H2O2-mediated oxidative stress. Free Radical Biol. Med. 2017; 108:354-361. doi: 10.1016/j.freeradbiomed.2017.04.001. PMID: 28389407
  • Zahra A, Fath MA, Opat E, Mapuskar KA, Bhatia SK, Ma DC, Rodman SN, Snyders TP, Chenard CA, Eichenberger-Gilmore JM, Bodeker KL, Ahmann L, Smith BJ, Vollstedt SA, Brown HA, Abu Hejleh T, Clamon GH, Berg DJ, Szweda LI, Spitz DR, Buatti JM, and Allen BG. Consuming a ketogenic diet while receiving radiation and chemotherapy for locally advanced lung and pancreatic cancer: the University of Iowa experience of two phase I clinical trials. Radiat. Res. 2017; 187(6):743-754. doi: 10.1667/RR14668.1. PMID: 28437190
  • Brandt KE, Falls KC, Schoenfeld JD, Rodman SN, Gu Z, Zhan F, Cullen JJ, Wagner BA, Buettner GR, Allen BG, Berg DJ, Spitz DR, and Fath MA: Augmentation of intracellular iron using iron sucrose enhances the toxicity of pharmacological ascorbate in colon cancer cells. Redox Biol. 2018; 14:82-87. doi: 10.1016/j.redox.2017.08.017. PMID: 28886484
  • Mapuskar KA, Flippo KH, Schoenfeld JD, Riley DP, Strack S, Abu Hejleh T, Furqan M, Monga V, Domann FE, Buatti JM, Goswami PC, Spitz DR, and Allen BG: Mitochondrial superoxide increases age-associated susceptibility of human dermal fibroblasts to radiation and chemotherapy. Cancer Res. 2017; 77(18):5054-5067. doi: 10.1158/0008-5472.CAN-17-0106. PMID: 28765155.
  • Schoenfeld JD, Sibenaller ZA, Mapuskar KA, Monga V, Milhem M, Spitz DR, Allen BG: Redox active metals mediate the increased efficacy of pharmacological ascorbate in combination with gemcitabine or radiation in pre-clinical sarcoma models. Redox Biol 2018; 14:417-422. doi: 10.1016/j.redox.2017.09.012. PMID: 29069637
  • Rashmi R, Huang X, Floberg J, Elhammali AE, McCormick ML, Patti GJ, Spitz DR, and Schwarz JK: Radiation-resistant cervical cancers are sensitive to inhibition of glycolysis and redox metabolism. Cancer Res. (in press 2018)
  • Heer CD, Davis AB, Riffe DB, Wagner BA, Falls KC, Allen BG, Buettner GR, Beardsley RA, Riley DP, and Spitz DR: Superoxide dismutase mimetic GC4419 enhances the oxidation of pharmacological ascorbate and its anticancer effects in an H2O2-dependent manner. Antioxidants (in press 2018).

Complete publications | Google Scholar | Pubmed

Honors, Awards and Organizations

  • 1987 Young Investigator Travel Award - Radiation Research Society
  • 1990 Young Investigator Award - International Society for Free Radical Research/The Oxygen Society.
  • 2001 Editorial Board - Free Radical Biology and Medicine
  • 2006-2010 Member NCI/NIH Radiation Therapeutics and Biology Study Section
  • 2008 Leader - Free Radical Metabolism and Imaging Program, Holden Comprehensive Cancer Center, The University of Iowa
  • 2008 Director of Radiation and Free Radical Research Core Laboratory, Holden Comprehensive Cancer Center, The University of Iowa
  • 2008 Director Free Radical and Radiation Biology Program, Department of Radiation Oncology, The University of Iowa
  • 2008-present   Editorial Board – Cancer Letters
  • 2013-present   Editorial Board – Radiation Research
  • 2013-present   Editorial Board – Cancer Research
  • 2014-present Tumor Cell Biology Study Section 

Education

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