My laboratory is interested in DNA topoisomerases as targets for antineoplastic therapy.  Research efforts include both the molecular and clinical pharmacology of drugs that interact with topoisomerases.  We are interested in cellular and clinical mechanisms of resistance to topoisomerase I-targeting drugs such as the camptothecins, as well as strategies to modulate the effects of these drugs in patients.  This work led to the concept of sequential topoisomerase targeting in cancer patients, which we are currently investigating in patients with leukemia.  Other work in the laboratory led to the identification of a novel topoisomerase I-binding RING protein, which we named “topors.”  Topors functions as both a ubiquitin ligase and a small ubiquitin-related modifier (SUMO) ligase and may be involved in the drug-induced degradation of topoisomerase I that is associated with resistance to camptothecin.  Topors associates with promyelocytic leukemia nuclear bodies, which are implicated in carcinogenesis.  Additional data indicate that topors protein and mRNA expression are commonly diminished in cancer tissues versus matched normal tissues, suggesting that topors functions in the suppression of carcinogenesis.  Studies of topors biology are a major current focus of the laboratory. 

	Topors functions as an E3 ubiquitin ligase with specific E2 enzymes and ubiquitinates p53. Rajendra R, Malegaonkar D, Pungaliya P, Marshall H, Rasheed Z, Brownell J, Liu LF, Lutzker S, Saleem A, Rubin EH. J Biol Chem. 2004 Jul 9 [Epub ahead of print]
	Epothilones: mechanism of action and biologic activity. Goodin S, Kane MP, Rubin EH. J Clin Oncol. 2004 May 15;22(10):2015-25.
	The topoisomerase I- and p53-binding protein topors is differentially expressed in normal and malignant human tissues and may function as a tumor suppressor. Saleem A, Dutta J, Malegaonkar D, Rasheed F, Rasheed Z, Rajendra R, Marshall H, Luo M, Li H, Rubin EH. Oncogene. 2004 Jul 8;23(31):5293-300.
	Development of a bioanalytical liquid chromatography method for quantitation of 9-nitrocamptothecin in human plasma. Gounder MK, Sun SL, Sands H, Lin Y, Shih WJ, Gu Z, Charles-Williams S, Roychowdhury M, Rajendra R, Rubin EH. J Chromatogr B Analyt Technol Biomed Life Sci. 2004 Jan 5;799(1):63-72.