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University of Colorado Denver

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David Ross, PhD

Chair, Department of Pharmaceutical Sciences, Professor of Toxicology

Mailing address:

University of Colorado School of Pharmacy
Mail Stop C238
12850 E. Montview Blvd. V20-2132A
Aurora, CO 80045

Office Location:

Pharmacy and Pharmaceutical Sciences Building (V20)
Second Floor
Room 2132A

Lab Location:

Pharmacy and Pharmaceutical Sciences Building (V20)
Second Floor
Room 2470A/D

Contact:

Affiliation:

  • Member, University of Colorado Cancer Center

Training and Education:

  • BSc, University of Aston in Birmingham, England (Pharmacy, Honors)
  • PhD, University of Aston in Birmingham, England (Pharmaceutical Chemistry)
  • MRPS, Member of the Royal Pharmaceutical Society 1979- ; DABT, Diplomate of the American Board of Toxicology, 1993

Research Interests:

Quinones, quinone reductases (NQO1 and 2), selective toxicity of antitumor agents, drug development, targeting of antitumor agents, pharmacogenetics, pharmacogenomics.
My laboratory is focused on understanding mechanisms underlying the toxicity of quinones. We then apply that knowledge to a number of different projects in antitumor drug development, environmental toxicology and neurodegeneration. Current projects include:

  1. Targeting the elevated levels of  NQO1 in human tumors for the development of quinone based alkylating agents and Hsp90 inhibitors.
  2. Utilizing the unique biochemistry of pancreatic tumors to develop novel quinone based therapies.  
  3. Understanding the contribution of dopamine derived quinones to proteasomal inhibition and protein aggregation in Parkinson’s disease.
  4. Defining the role of benzene derived quinones and NQO1 polymorphisms in benzene induced leukemia.

Teaching:

  • Professional/Graduate Program: toxicology, drug metabolism, pharmacogenetics, molecular targets in cancer

Some Recent Publications:

  • Reigan, P., Colucci, M.A., Siegel, D., Chilloux, A., Moody, C.J. and Ross, D. Development of indolequinone mechansism based inhibitors of NADPH:quinone oxidoreductase 1 (NQO1). NQO1 inhibition and growth inhibitory activity  in human pancreatic MIA PaCa-2 cancer cells. Biochemistry,  46, 5941-5950, 2007
  • Colucci, M.A., Reigan, P.,  Siegel, D., Chilloux, A., Ross, D  and Moody, C.J. The synthesis and evaluation of 3-aryloxymethyl-1,2-dimethylindole-4,7-diones as mechanism based inhibitors of NADPH:quinone oxidoreductase 1 (NQO1). J. Med. Chem 50, 5780-5789, 2007.  
  • Guo, W., Reigan, P. Siegel, D. and Ross, D. Enzymatic reduction and glutathione conjugation of benzoquinone ansamycin Hsp90 inhibitors. Relevance for toxicity and mechanism of action. Drug Metab. Disp., 36 2050-7 2008
  • Yan, C., Kepa, J.K. Siegel, D., Stratford, I.J. and Ross, D. Dissecting the role of multiple reductases in bioactivation and cytotoxicity of RH1  Mol. Pharmacol.  74, 1657-1665 2008. 
  • Yan, C., Shieh, B., Reigan, P., Zhang, Z., Colucci, M.A., Chilloux, A., Newsome, J.J., Siegel, D., Chan, D., Moody, C.J. and Ross, D. Potent activity of indolequinones against human pancreatic cancer. Identification of thioredoxin reductase as a potential target.  Mol. Pharmacol. 76 1-9, 2009
  • Zhou, H., Kepa, J.K., Siegel, D., Miura, S., Hiraki, Y. and Ross, D.  The benzene metabolite hydroquinone upregulates chodromodulin 1 and inhibits tube formation in human bone marrow endothelial cells. Mol. Pharmacol., 76, 579-87, 2009.
  • Zhou, H., Dehn, D., Kepa, J.K.Siegel, D., Scott, D.E. Tan, W. and Ross, D. NQO1-compromised human bone marrow endothelial cells exhibit decreased adhesion molecule expression and CD34+ hematopoietic cell adhesion. J. Pharmacol. Exptl. Ther. 334, 1-9 2010.

  • Ross D. and Zhou H. Relationships between metabolic and non metabolic susceptibility factors in benzene toxicity. Chem.Biol. Interact. 184, 222-228, 2010

Recent Reviews:

  • Ross, D. NQO1 Genecard. Atlas Genet. Cytogenet. Oncol. Haematol.,  Jan 2002,  update, 2004
    URL http://www.infobiogen.fr/services/chromcancer/Genes/NQO1ID375.html
  • Ross D. and Siegel D. NAD(PH:quinone oxidoreductase 1 (NQO1, DT-diaphorase). Functions and pharmacogenetics. In Methods in Enzymology, Qunones and Quinone Enzymes Part B,  382, 115-143, 2004.
  • Ross D. Quinone reductases. Multitasking in the metabolic world. Drug Metabolism Reviews 36 639-654, 2004.
  • Ross, D. Functions and distribution of NQO1 in human bone marrow: Potential clues to benzene toxicity. Chem. Biol. Interact.  153/4, 137-146, 2005
  • Vasiliou, V., Ross, D. and Nebert, D.W. Update of the NAD(P)H:quinone oxidoreductase (NQO) gene family. Human Genomics,  2  (5), 1-7, 2006.