Education:
BS 1964 Chemistry - Case Institute of Technology, Cleveland, Ohio
MS 1967 Chemistry - Univeristy of Southern California
PhD 1970 Chemistry - University of Southern California
Postdoctoral Research Fellowship:
1970-1973 University of Wisconsin
Started at USC: 1976
Research Topics: Cancer Cell Biology, Protein Chemistry/Enzymology, DNA & RNA
Research Description
The work in this laboratory is directed at understanding the mechanisms by which cytotoxic anti-cancer drugs interact with their intracellular targets and the molecular factors and events determining response of tumors to drugs. Innate drug sensitivity of tumors as well as acquired resistance may be due to quantitative and qualitative changes in the expression of genes of target enzymes and activating enzymes. We have developed methods for quantitating gene expression by PCR and for rapid mutation detection by RNA conformational analysis. The latter technique is being used to investigate the role of mutations in acquired drug resistance. By using quantitative PCR, we have shown substantial variation among tumors in the degree of expression of genes of drug-targeted enzymes such as thymidylate synthase. Studies are under way to identify factors that alter the normal expression of these genes in cancer cells.
We are also studying RNA splicing as a potential target of anti-cancer drugs. Splicing requires RNA molecules to be in a native conformation stabilized by specific base-pairing and tertiary interactions. We are testing the hypothesis that the widely used anti-cancer drug 5-fluorouracil, which has base-pairing properties different than those of uracil, is an inhibitor of mRNA precursor splicing. The effects of this compound on RNA conformation, kinetics of splicing, spliceosome assembly, and gene expression are being evaluated.
Selected Publications
Theisen J, Danenberg K, Ott K, Becker K, Danenberg P, Stein HJ, Siewert JR. - Predictors of response and survival for neoadjuvant treated patients with esophageal adenocarcinoma. - Dis Esophagus [ 2008 ] Apr 22; . PubMed
Gutschow CA, Vallbohmer D, Stolte M, Oh D, Danenberg K, Danenberg P, Schneider PM, Holscher AH. - Adenocarcinoma developing in de novo Barrett's mucosa in the remnant esophagus after esophagectomy: clinical and molecular assessment. - Dis Esophagus [ 2008 ] 21(3):E6-8 . PubMed
Mori R, Wang Q, Quek ML, Tarabolous C, Cheung E, Ye W, Groshen S, Hawes D, Togo S, Shimada H, Danenberg KD, Danenberg PV, Pinski JK. - Prognostic value of the androgen receptor and its coactivators in patients with D1 prostate cancer. - Anticancer Res [ 2008 ] Jan-Feb;28(1B):425-30 . PubMed
Kuramochi H, Hayashi K, Uchida K, Nakajima G, Hatori T, Danenberg KD, Danenberg PV, Yamamoto M. - High intratumoral dihydropyrimidine dehydrogenase mRNA levels in pancreatic cancer associated with a high rate of response to S-1. - Cancer Chemother Pharmacol [ 2008 ] Feb 29; . PubMed
Kobayashi H, Sugihara K, Uetake H, Higuchi T, Yasuno M, Enomoto M, Kuramochi H, Lenz HJ, Danenberg KD, Danenberg PV. - Messenger RNA expression of vascular endothelial growth factor and its receptors in primary colorectal cancer and corresponding liver metastasis. - Ann Surg Oncol [ 2008 ] Apr;15(4):1232-8 . PubMed
Banki F, Mason RJ, Hagen JA, Demeester SR, Lipham JC, Danenberg K, Danenberg P, Demeester TR. - Plasma DNA: a molecular marker of surgical insult and postoperative recovery in esophageal cancer. - Eur Surg Res [ 2008 ] 40(3):273-8 . PubMed
Kuramochi H, Tanaka K, Oh D, Lehman BJ, Dunst CM, Yang DY, De Meester SR, Hagen JA, Danenberg KD, De Meester TR, Danenberg PV. - Thymidylate synthase polymorphisms and mRNA expression are independent chemotherapy predictive markers in esophageal adenocarcinoma patients. - Int J Oncol [ 2008 ] Jan;32(1):201-8 . PubMed
Azuma M, Shi M, Danenberg KD, Gardner H, Barrett C, Jacques CJ, Sherod A, Iqbal S, El-Khoueiry A, Yang D, Zhang W, Danenberg PV, Lenz HJ. - Serum lactate dehydrogenase levels and glycolysis significantly correlate with tumor VEGFA and VEGFR expression in metastatic CRC patients. - Pharmacogenomics [ 2007 ] Dec;8(12):1705-13 . PubMed
Vallbohmer D, Marjoram P, Kuramochi H, Shimizu D, Jung H, DeMeester SR, Oh D, Chandrasoma PT, Danenberg KD, DeMeester TR, Danenberg PV, Peters JH. - Towards the molecular characterization of disease: comparison of molecular and histological analysis of esophageal epithelia. - J Gastrointest Surg [ 2007 ] Sep;11(9):1095-104 . PubMed
Vallbohmer D, Yang DY, Kuramochi H, Shimizu D, Danenberg KD, Lindebjerg J, Nielsen JN, Jakobsen A, Danenberg PV. - DPD is a molecular determinant of capecitabine efficacy in colorectal cancer. - Int J Oncol [ 2007 ] Aug;31(2):413-8 . PubMed
