Douglas Spitz- Professor

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
Tel: 319-335-8001
Fax:319-335-8039
email:douglas-spitz@uiowa.edu

 

 

 

 

 

 

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 increase 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 recently received R21 support from the NCI to initiate clinical trials using ketogenic diets to enhance cancer therapy based on these basic science observations. Recently 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 Biosciences Graduate Program and the Free Radical and Radiation Biology Graduate Program at the University of Iowa as well as the director of the Radiation and Free Radical Research Core Laboratory and the Free Radical Cancer Biology Program in the Holden Comprehensive Cancer Center. He is also the chairman of the Carver College of Medicine Research Committee at the University of Iowa that reviews 50 pilot grants/year from young investigators. He is also the PI of an NCI funded T32 Training Program in Free Radical and Radiation Biology, an NCI RO1 grant, an NCI R21 grant, and a DOE grant.

Example Publications | Full CV

  • Lee YJ, Galoforo SS, Berns CM, Chen JC, Davis BH, Sim JE, Corry PM, and Spitz DR: Glucose deprivation-induced cytotoxicity and alterations in mitogen-activated protein kinase activation are mediated by oxidative stress in multidrug- resistant human breast carcinoma cells. J Biol Chem 1998; 273:5294-5299. PMID: 9478987.

  • 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.
  • Goswami PC, Sheren J, Albee LD, Parsian AJ, Sim JE, Ridnour LA, Higashikubo R, Hunt CR, and Spitz DR: Cell cycle coupled variation in Topoisomerase IIα mRNA is regulated by the 3’-untranslated region: possible role of redox sensitive protein binding in mRNA stability. J Biol Chem 2000; 275:38384-38392. PMID: 10986283.
  • 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; 280:4254-4263. PMID: 15561720.
  • 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.
  • 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: 184559877.
  • 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 J2009; 418:29-37. PMID: 18937644.
  • 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. PMID: 20129246.
  • 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.
  • 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. PMID: 22081025.
  • 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. PMID: 21482679.
  •  He C, Murthy S, McCormick ML, Spitz DR, Ryan AJ, and Carter AB: Mitochondrial Cu,Zn-Superoxide Dismutase Mediates Pulmonary Fibrosis by Augmenting H2O2 Generation. J Biol Chem. 2011; 286(17):15597-607.  PMID: 21393238 [PubMed - in process]
  • 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. PMID: 22041456.

 

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
  • 2005 Leader - Free Radical Cancer Biology Program, Holden Comprehensive Cancer Center, The University of Iowa
  • 2005 Director of Radiation and Free Radical Research Core Laboratory, Holden Comprehensive Cancer Center, The University of Iowa
  • 2006 Member NCI/NIH Radiation Therapeutics and Biology Study Section
  • 2008 Director Free Radical and Radiation Biology Program, Department of Radiation Oncology, The University of Iowa
  • 2008-present   Editorial Board – Cancer Letters


Education

  • PhD, 1984, Radiation Biology, Minor-Biochemistry, University of Iowa, Iowa City, Iowa

  • B.A., Biology/Sociology, 1978, Grinnell College, Grinnell, Iowa