Faculty / Research
Thomas Rosenquist, PhDResearch Assistant Professor
Ph.D., University of Wisconsin-Madison
Postdoctoral, University of California, San Francisco
Genetic Analysis of Mammalian Oxidative DNA Damage Repair
We are using mouse genetics to investigate the links between DNA damage and carcinogenesis, and degenerative diseases.
Aristolochic acid (AA) is a plant-derived nephrotoxin and carcinogen found in herbal remedies using Aristolochia throughout the world. Aristolochic acid nephropathy (AAN) is a renal disorder, marked by proximal tubule atrophy and interstitial fibrosis, that leads to end-stage renal disease in approximately 5% of people exposed to AA. About half of these people also develop cancer of the upper urinary tract. AA is also thought to be the environmental component of Balkan Endemic Nephropathy (BEN) affecting rural farmers in the Danube River Basin. While direct damage of DNA with AA-DNA adducts has been shown to pro-mutagenic and leads to cancer, the mechanism of AA-induced nephrotoxicity is not clear.
Working with Dr. Arthur Grollman’s group we have developed mouse models of AAN and are working on the genetic factors underlying sensitivity to AA nephrotoxicity and DNA damage. The goal is to relate the genetic factors found in the mouse to human genetic predisposition to AA-sensitivity.
Grollman AP, Shibutani S, Moriya M, Miller F, Wu L, Moll U, Suzuki N, Fernandes A, Rosenquist T, Medverec Z, Jakovina K, Brdar B, Slade N, Turesky RJ, Goodenough AK, Rieger R, Vukelić M, Jelaković B. (2007) Aristolochic acid and the etiology of endemic (Balkan) nephropathy. PNAS (USA) 104(29):12129-34.
Huang F, Clifton J, Yang X, Rosenquist T, Hixson D, Kovac S, Josic D. SELDI-TOF as a method for biomarker discovery in the urine of aristolochic-acid-treated mice. (2009) Electrophoresis. 30(7):1168-74.
Shibutani S, Bonala RR, Rosenquist T, Rieger R, Suzuki N, Johnson F, Miller F, Grollman AP. (2009) Detoxification of aristolochic acid I by O-demethylation; less nephrotoxicity and genotoxicity of aristolochic acid Ia in rodents. Int J Cancer. 2009 Dec 28 [Epub ahead of print]
Rosenquist TA, Einolf HJ, Dickman KG, Wang L, Smith A, Grollman AP. (2010) Cytochrome P450 1A2 detoxicates aristolochic acid in the mouse. Drug Metab Dispos. 2010 Feb 17. [Epub ahead of print]