David Ross, Ph.D.
Chair, Department of Pharmaceutical Sciences
Professor of Toxicology
Mailing address:
4200 E. 9th Ave, C238
Denver, CO 80262
Telephone:
Voice: 303-315-6077
Lab: 303-315-6078
Fax: 303-315-0274
E-Mail:David.Ross@uchsc.edu
Affiliation:
Member, University of Colorado Cancer Center
Training and Education:
B.Sc., University of Aston in Birmingham, England (Pharmacy, Honors)
Ph.D., 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
Recent research articles:
Inayat-Hussain, S. and Ross, D. The intrinsic pathway of hydroquinone-induced apoptosis occurs via both caspase dependent and caspase-independent mechanisms. Chem. Res.Toxicol. 3, 420-427, 2005
Dehn, D, Inayat-Hussain, S.. and Ross, D. RH1 Induces Cellular Damage in an NQO1-dependent Manner: Relationship Between DNA Cross-linking, Cell Cycle Perturbations and Apoptosis. J. Pharmacol. Expt. Ther. 313 771-779 2005.
Guo, W., Reigan, P., Siegel, D. Zirrolli, J., Gustafson, D. And Ross, D. Formation of 17-AAG hydroquinone by NAD(P)H:quinone oxidoreductase 1 (NQO1): Role of 17-AAG hydroquinone in Hsp90 inhibition. Cancer Research, 65, 10006-10015, 2005
Dehn, D.L., Siegel, D. Zafar, K.S., Reigan, P., Swann, E., Moody, C.J. and Ross, D. ES936, a mechanism based inhibitor of NQO1 exhibits activity against human pancreatic cancer in-vitro and in-vivo. Mol. Cancer Therapeutics 7, 1702-9, 2006
Zafar, K.S., Siegel, D. and Ross, D. A potential role for cyclized quinones derived from dopamine, DOPA and DOPAC in proteasomal inhibition. Mol. Pharmacol. E pub Jun 21st 2006.
Guo, W., Reigan, P., Siegel, D. Zirrolli, J., Gustafson, D. And Ross, D. The bioreduction of a series of benzoquinone anamycins by NQO1 to more potent Hsp90 inhibitors, the hydroquinone ansamycins. Mol. Pharmacol. In press 2006.
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.
Last updated: 6/25/07