Dr. Yalowich’s lab focuses on the mechanisms of action and resistance to DNA topoisomerase II (topo II)-targeted agents, such as the anticancer agent etoposide (VP-16). Recent work has characterized alternative RNA processing of topo IIα pre-mRNA that results in decreased expression of full-length topo II in acquired resistance to VP-16. Strategies to circumvent resistance involve CRISPR/Cas9 gene editing to restore proper RNA splicing function in resistant cells. A second project involves the role of micro-RNAs as determinants of drug resistance. Finally, the use of nutritional antioxidants (such as vitamin C) is under investigation as a strategy to prevent cancer-causing effects of topo II-targeted agents, which can arise in patients years after therapy is complete.
- PhD, 1980, State University of New York at Buffalo, Biochemical Pharmacology
- BA, 1974, Lehigh University, Chemistry-Biology
- 2017-present: Secretary-Treasurer; Division for Cancer Pharmacology; American Society for Pharmacology and Experimental Therapeutics
- 2016-present: Editorial Board; Journal of Pharmacology and Experimential Therapeutics
- 2015-present: Editorial Board; Cancer Biology and Therapy
- 2015-2017: Chair; Division of Pharmacology, College of Pharmacy, The Ohio State University
- 2012-2016: Chair; Molecular Targets for Cancer Intervention [ZRG BMCT-C (01)] study section, National Cancer Institute (NCI/NIH)
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- Li L, Okumu A, Dellos-Nolan S, Li Z, Karmahapatra S, English A, Yalowich JC, Wozniak DJ, Mitton-Fry MJ. Synthesis and anti-staphylococcal activity of novel bacterial topoisomerase inhibitors with a 5-amino-1,3-dioxane linker moiety. Bioorg Med Chem Lett. 2018 Aug 01;28(14):2477-2480.
- Woodard JL, Huntsman AC, Patel PA, Chai HB, Kanagasabai R, Karmahapatra S, Young AN, Ren Y, Cole MS, Herrera D, Yalowich JC, Kinghorn AD, Burdette JE, Fuchs JR. Synthesis and antiproliferative activity of derivatives of the phyllanthusmin class of arylnaphthalene lignan lactones. Bioorg Med Chem. 2018 05 15;26(9):2354-2364.
- Kanagasabai R, Karmahapatra S, Kientz CA, Yu Y, Hernandez VA, Kania EE, Yalowich JC, Elton TS. The Novel C-terminal Truncated 90-kDa Isoform of Topoisomerase IIα (TOP2α/90) Is a Determinant of Etoposide Resistance in K562 Leukemia Cells via Heterodimerization with the TOP2α/170 Isoform. Mol Pharmacol. 2018 May;93(5):515-525.
- Kanagasabai R, Serdar L, Karmahapatra S, Kientz CA, Ellis J, Ritke MK, Elton TS, Yalowich JC. Alternative RNA Processing of Topoisomerase IIα in Etoposide-Resistant Human Leukemia K562 Cells: Intron Retention Results in a Novel C-Terminal Truncated 90-kDa Isoform. J Pharmacol Exp Ther. 2017 Jan;360(1):152-163.
- Nagre N, Wang S, Kellett T, Kanagasabai R, Deng J, Nishi M, Shilo K, Oeckler RA, Yalowich JC, Takeshima H, Christman J, Hubmayr RD, Zhao X. TRIM72 modulates caveolar endocytosis in repair of lung cells. Am J Physiol Lung Cell Mol Physiol. 2016 Mar 01;310(5):L452-64.
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