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Douglas D. Thomas, Ph.D.Joanna Burdette

Associate Professor
Department of Medicinal Chemistry and Pharmacognosy

University of Illinois at Chicago
College of Pharmacy
900 S. Ashland Avenue (M/C 870)
Chicago IL 60607

Office: 4352 MBRB
Office Phone: 312-996-6156
Lab: 4356-60/4331/3350 MBRB
Lab Phone:
Fax Number: 312-996-7107
E-mail address: ddthomas@uic.edu
Lab website: http://thomaslab.publish.uic.edu/

Education:

Washington State University, Pullman, WA, B.S. in Zoology, 1987-1992
Louisiana State University Health Sciences Center, New Orleans, LA, Ph.D. in Pathology, 1994-2000
National Institutes of Health, National Cancer Institute, Bethesda, MD, Post-Doctoral in Radiation Biology, 2001-2007

Research Interests:

Initially, our investigations focused on understanding the chemical biology and signaling properties of the free radical nitric oxide (•NO).  Since its initial discovery as “endothelium-derived relaxing factor” in the 1980s, the understanding of •NO in biological systems has become vastly more complex.  It is now known to be involved in numerous physiological functions ranging from smooth muscle relaxation and immune defenses to antioxidant activity and neuronal transmission.  In addition to its many physiologic functions, •NO signaling is central to the etiology and progression of countless chronic diseases including cancer. 

More specifically, the overarching goal of my research program is to elucidate novel biochemical and signaling properties of •NO and explain their contributions to the pathophysiology of cancer.  Although there are numerous and well-studied means of •NO signaling, our findings have uncovered a novel mechanism of •NO signaling by revealing that the interactions of •NO with cellular iron pools can have dramatic effects on cell biology.  Our research examines the cross-talk between •NO and iron signaling within the cell in an effort to elucidate mechanisms that underlie phenotypic outcomes. 

Identification of •NO as an endogenously produced epigenetic regulatory molecule is the most significant finding to emerge from our studies.  Post-translational modifications of histone lysine residues are an important epigenetic regulator of chromatin structure and gene transcription.  Recently completed studies by our group revealed 3 novel and distinct mechanisms whereby •NO can affect post-translational histone modifications: direct inhibition of histone demethylase activity, reduction in iron cofactor availability, and changes in the expression of histone modifying enzymes.  These results have the potential to fundamentally change the way we view this diatomic radical.  Since evidence is continually emerging that demonstrates •NO is an important regulator in numerous tumor types, and iron is ubiquitous, our research is helping establish a coherent biochemical link between •NO, iron, epigenetic modifications, and tumor pathophysiology. 

My current program, funded by R01 GM094175, focuses on three main areas that will expand our understanding of •NO chemical biology and cancer etiology:

  1. Mechanisms of epigenetic regulation by •NO (DNA and Histone)
  2. The reaction of •NO with iron and the consequences of dinitrosyliron complex formation
  3. The relationship between hypoxia and •NO-driven tumor cell behavior

Select Publications:

  1. Hickok J.R.; Vasudevan D.; Antholine W.E.; Thomas D.D., Nitric Oxide Modifies Global Histone Methylation by Inhibiting Jumonji C Domain-containing Demethylases. J Biol Chem. 2013 May 31;288(22):16004-15. PMID: 23546878 [abstract]
  2. Hickok, J.R.; Vasudevan, D.; Jablonski, K.; Thomas, D.D., Oxygen dependence of nitric oxide-mediated signaling. Redox Biology Vol.1 January 14th, 2013 [abstract]
  3. Thomas, D.D., In: G.C.K. Roberts (ed.), Oxidative Stress. Encyclopedia of Biophysics, Springer-Verlag Berlin Heidelberg, pp. 1813-1818, 2013.
  4. Hickok, J. R.; Vasudevan, D.; Thatcher, G. R.; Thomas, D. D., Is S-nitrosocysteine a true surrogate for nitric oxide? Antioxid Redox Signal. 2012 [abstract]
  5. Hickok, J. R.; Sahni, S.; Shen, H.; Arvind, A.; Antoniou, C.; Fung, L. W.; Thomas, D. D., Dinitrosyliron complexes are the most abundant nitric oxide-derived cellular adduct: biological parameters of assembly and disappearance. Free Radic Biol Med 2011, 51, (8), 1558-66. [abstract]
  6. Hickok, J. R.; Sahni, S.; Mikhed, Y.; Thomas, D. D., Nitric oxide suppresses tumor cell migration through N-Myc downstream-regulated gene-1 (NDRG1) expression: role of chelatable iron. J Biol Chem 2011, 286, (48), 41413-24. [abstract]
  7. Hickok, J. R.; Thomas, D. D., Nitric oxide and cancer therapy: the emperor has NO clothes. Curr Pharm Des 2010, 16, (4), 381-91. [abstract]
  8. Thomas, D. D.; Ridnour, L. A.; Isenberg, J. S.; Flores-Santana, W.; Switzer, C. H.; Donzelli, S.; Hussain, P.; Vecoli, C.; Paolocci, N.; Ambs, S.; Colton, C. A.; Harris, C. C.; Roberts, D. D.; Wink, D. A., The chemical biology of nitric oxide: implications in cellular signaling. Free Radic Biol Med 2008, 45, (1), 18-31. [abstract]
  9. Thomas, D. D.; Ridnour, L. A.; Espey, M. G.; Donzelli, S.; Ambs, S.; Hussain, S. P.; Harris, C. C.; DeGraff, W.; Roberts, D. D.; Mitchell, J. B.; Wink, D. A., Superoxide fluxes limit nitric oxide-induced signaling. J Biol Chem 2006, 281, (36), 25984-93. [abstract]
  10. Thomas, D. D.; Espey, M. G.; Pociask, D. A.; Ridnour, L. A.; Donzelli, S.; Wink, D. A., Asbestos redirects nitric oxide signaling through rapid catalytic conversion to nitrite. Cancer Res 2006, 66, (24), 11600-4. [abstract]
  11. Thomas, D. D.; Espey, M. G.; Ridnour, L. A.; Hofseth, L. J.; Mancardi, D.; Harris, C. C.; Wink, D. A., Hypoxic inducible factor 1alpha, extracellular signal-regulated kinase, and p53 are regulated by distinct threshold concentrations of nitric oxide. Proc Natl Acad Sci U S A 2004, 101, (24), 8894-9. [abstract]
  12. Thomas, D. D.; Espey, M. G.; Vitek, M. P.; Miranda, K. M.; Wink, D. A., Protein nitration is mediated by heme and free metals through Fenton-type chemistry: an alternative to the NO/O2- reaction. Proc Natl Acad Sci U S A 2002, 99, (20), 12691-6. [abstract]
  13. Thomas, D. D.; Liu, X.; Kantrow, S. P.; Lancaster, J. R., Jr., The biological lifetime of nitric oxide: implications for the perivascular dynamics of NO and O2. Proc Natl Acad Sci U S A 2001, 98, (1), 355-60. [abstract]
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