Douglas Spitz

2011-2014

2000-2006

1993-2000

1989-1992

1987-1989

1984-1987

1979-1984

1974-1978

• free radicals and oxidative stress in biology and medicine;
• the differential metabolic oxidative stress associated with glucose deprivation-induced cytotoxicity in human cancer versus normal cells as well as the relationship of this metabolic stress to cancer biology and the design of new therapeutic interventions;
• the study of phenotypic changes associated with oxidative stress-resistant mammalian cell lines, nitric oxide toxicology, molecular mechanisms of resistance to oxidative stress in cancer biology, redox regulation of the cell cycle, redox regulation of signal transduction, radiation biology, and redox regulation of gene expression; and,
• the overall goal of my research is to use a basic science understanding of mechanisms associated with free radical biology to elucidate novel methods for manipulating clinically significant outcomes in areas of medicine relevant to cancer biology and degenerative diseases associated with aging.

Coleman MC, Olivier AK, Jacobus JA, Mapuskar KA, Mao G, Martin SM, Riley DP, Gius D, and Spitz DR: Superoxide mediates acute liver injury in irradiated mice lacking Sirtuin 3. Antioxidants and Redox Signaling 2014; 20(9):1423-35. PMID:23919724.

Spitz DR and Hauer-Jensen M: Ionizing radiation-induced responses: where free radical chemistry meets redox biology and medicine. Antioxid Redox Signal. 2014; 20(9):1407-9. PMID:24354361.

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-senior authors).

Jacobus JA, Duda CG, Coleman MC, Martin SM, Mapuskar K, Mao G, Smith BJ, Aykin-Burns N, Guida P, Gius D, Domann FE, Knudson CM, and Spitz DR: Low dose radiation-induced enhancement of thymic lymphomagenesis in Lck-Bax mice is dependent on LET and gender. Radiat Res. 2013; 180(2):156-65. PMID:23819597.

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: 22041456159.

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. PMID: 22100505.

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. PMID: 21844013.

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.

Aykin-Burns N, Slane BG, Liu ATY, Owens KM, O’Malley MS, Smith BJ, Domann FE, and Spitz DR: Sensitivity to low dose/low LET ionizing radiation in mammalian cells harboring mutations in succinate dehydrogenase subunit C is governed by mitochondrial derived reactive oxygen species. Radiat. Res. 2011; 175(2):150-8. PMID: 21268708.

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. *- denotes Co-first Authors.

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. PMID: 18937644.

Dayal D, Martin SM, Limoli CL, Spitz DR. Hydrogen peroxide mediates the radiation-induced mutator phenotype in mammalian cells. Biochem J 2008; 413(1):185-191. PMID: 18352860.

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.

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.