Thomas Rosenquist, PhD (Research Associate Professor)
Ph.D., University of Wisconsin-Madison
Postdoctoral, University of California, San Francisco
Many cancers are preventable in that they are induced by environmental chemicals. Biomarkers of such exposures are needed to guide public health decisions. We are building on groundbreaking work with the plant carcinogen, aristolochic acid to develop a platform that links damaged DNA bases (adducts) to mutational signatures found in tissue DNA. Specific DNA-adducts, such as those from aristolochic acid and many other chemicals, can be long-lived and serve as excellent biomarkers of exposure. Also, DNA-adducts can leave specific patterns of mutations that are duplicated and maintained in cellular DNA for the lifetime of an individual. Such mutational signatures can provide a diagnostic record of a person’s exposure to mutagenic agents and are evidence of the pathological consequences of those exposures. We are collaborating with University of Minnesota in this approach, called “adductomics” that allow mass-spectroscopic identification and quantification of all the DNA adducts in a patient DNA sample. We have also developed next-gen sequencing analysis to identify the DNA mutations present in single cells of the tissue from which the DNA originated. The goal is to link mutational signatures of unknown etiology to the DNA damage that lead to their generation, and thus to the exposures responsible.
Aristolochic acid and its effect on different cancers in uro-oncology
Rebhan K, Ertl IE, Shariat SF, Grollman AP, Rosenquist T Current Opinion in Urology (2020)
Cell Opin Urol, (2020) 30(5):689-695, PMID: 32701724
Supervised mutational sigs predict etiological factors in cancer and reveal the tissue dependence of mutational processes.
Afsari B, Zhang YF, Li L, Kuo A, Danilova L, Favorov A, Rosenquist T, Grollman AP, Kinzler KW, Vogelstein B, Tomasetti C
eLife (2021) 10:e61082
Non-invasive detection of urothelial cancer through the analysis of driver gene mutations and aneuploidy.
Springer S, Chen C-H, Del Carmen Rodriguez Pena M, Li L, Douville C, Wang Y, Cohen J, Taheri D, Afsari B, Silliman N, Schaefer J, Ptak J, Dobbyn L, Papoli M, Kinde I, Tregnago AC, Bezerra SM, VandenBussche C, Fujita K, Ertoy D, Cunha IW, Yu L, Bivalacqua TJ, Grollman AP, Diaz Jr LA, Karchin R, Danilova L, Huang C-Y, Shun C-T, Turesky RJ, Yun BH, Rosenquist TA, Pu Y-S , Hruban R, Tomasetti C, Papadopoulos N, Kinzler KW, Vogelstein B, Dickman KG, Netto G J.
eLife, (2018) Mar 20;7. PMID: 29557778
Targeted and untargeted detection of DNA adducts of aromatic amine carcinogens in human bladder by ultra-performance liquid chromatography-high-resolution mass spectrometry.
Guo J, Villalta PW, Weight CJ, Bonala R, Johnson F, Rosenquist TA, Turesky RJ.
Chem Res Toxicol. Dec 17;31(12):1382-1397 (2018), PMID:30387604
Method for biomonitoring DNA adducts in exfoliated urinary cells by mass spectrometry.
Yun BH, Bellamri M, Rosenquist TA, Turesky RJ.
Anal Chem. Aug 21;90(16):9943-9950 (2018), PMID:30001485
Human liver-kidney model elucidates the mechanisms of aristolochic acidnephrotoxicity.
Chang S-Y, Weber EJ, Sidorenko VS, Chapron A, Yeung CK, Gao C, Mao Q, Shen D, Wang J, Rosenquist TA, Dickman KG, Neumann T, Grollman AP, Kelly EJ, Himmelfarb J, Eaton DL
JCI Insights 2(22) (2017) PMID: 29202460
A rapid throughput method to extract DNA from formalin-fixed paraffin-embedded tissues for biomonitoring carcinogenic DNA adducts.
Yun BH, Xiao S, Yao L, Krishnamachari S, Rosenquist TA, Dickman KG, Grollman AP, Murugan P, Weight CJ, Turesky RJ.
Chem Res Toxicol 30(12):2130-2139 (2017). PMID: 29120619
Tissues by Ultraperformance Liquid Chromatography-Tandem Mass Spectrometry.
Guo J, Yun BH, Upadhyaya P, Yao L, Krishnamachari S, Rosenquist TA, Grollman AP, Turesky RJ.
Anal Chem. May 3;88(9):4780-7 (2016). PMID:27043225
Multiclass Carcinogeneic DNA Adduct Quantification in formalin-Fixed Paraffin-Embedded Tissues by Ultraperformance Liquid Chromatography-Tandem Mass Spectrometry.Guo J, Yun BH, Upadhyaya P, Yao L, Krishnamachari S, Rosenquist TA, Grollman AP, Turesky RJ.
Anal Chem 88(9):4780-4787(2016). PMID: 27043225
Mutational signature of aristolochic acid: Clue to the recognition of a global disease.
Rosenquist TA, Grollman AP.
DNA Repair 44:205-211(2016). PMID: 27237586
Genome-wide quantification of rare somatic mutations in normal human tissues using massively parallel sequencing.
Hoang ML, Kinde I, Tomasetti C, McMahon KW, Rosenquist TA, Grollman AP, Kinzler KW, Vogelstein B, Papadopoulos N.
Proc Natl Acad Sci (2016). PMID: 27528664
Aristolochic acid in the etiology of renal cell carcinoma.
Hoang ML, Chen CH, Chen P-C, Roberts NJ, Dickman KG, Yun BH, Turesky RJ, Pu Y-S, Vogelstein B, Papadopoulos N, Grollman AP, Kinzler KW, Rosenquist TA.
Cancer Epidemiol Biomarkers Prev 113(35):9846-9851, (2016). PMID: 27555084