Jack Yalowich, PhD
Professional Interests
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.
Education
- 1980, PhD, University at Buffalo, State University of New York
- 1974, BA, Lehigh University
Honors
- 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)
- See more honors
Journal Articles
Hernandez VA, Carvajal-Moreno J, Papa JL, Shkolnikov N, Li J, Ozer HG, Yalowich JC, Elton TS. CRISPR/Cas9 Genome Editing of the Human Topoisomerase II Intron 19 5' Splice Site Circumvents Etoposide Resistance in Human Leukemia K562 Cells. Mol Pharmacol. 2021 Mar;99(3):226-241. doi: 10.1124/molpharm.120.000173. Epub 2021 Jan 14. PMID: 33446509; PMCID: PMC7919865.
Lu Y, Papa JL, Nolan S, English A, Seffernick JT, Shkolnikov N, Powell J, Lindert S, Wozniak DJ, Yalowich J, Mitton-Fry MJ. Dioxane-Linked Amide Derivatives as Novel Bacterial Topoisomerase Inhibitors against Gram-Positive Staphylococcus aureus. ACS Med Chem Lett. 2020 Oct 19;11(12):2446-2454. doi: 10.1021/acsmedchemlett.0c00428. PMID: 33335666; PMCID: PMC7734797.
Okumu A, Lu Y, Dellos-Nolan S, Papa JL, Koci B, Cockroft NT, Gallucci J, Wozniak DJ, Yalowich JC, Mitton-Fry MJ. Novel bacterial topoisomerase inhibitors derived from isomannide. Eur J Med Chem. 2020 Aug 1;199:112324. doi: 10.1016/j.ejmech.2020.112324. Epub 2020 Apr 28. PMID: 32402932.
Kania EE, Carvajal-Moreno J, Hernandez VA, English A, Papa JL, Shkolnikov N, Ozer HG, Yilmaz AS, Yalowich JC, Elton TS. hsa-miR-9-3p and hsa-miR-9-5p as Post-Transcriptional Modulators of DNA Topoisomerase II in Human Leukemia K562 Cells with Acquired Resistance to Etoposide. Mol Pharmacol. 2020 Mar;97(3):159-170. doi: 10.1124/mol.119.118315. Epub 2019 Dec 13. PMID: 31836624; PMCID: PMC6978698.
Elton TS, Ozer HG, Yalowich JC. Effects of DNA topoisomerase IIα splice variants on acquired drug resistance. Cancer Drug Resist. 2020;3(2):161-170. doi: 10.20517/cdr.2019.117. Epub 2020 Feb 27. PMID: 32566920; PMCID: PMC7304410.
Li L, Okumu AA, Nolan S, English A, Vibhute S, Lu Y, Hervert-Thomas K, Seffernick JT, Azap L, Cole SL, Shinabarger D, Koeth LM, Lindert S, Yalowich JC, Wozniak DJ, Mitton-Fry MJ. 1,3-Dioxane-Linked Bacterial Topoisomerase Inhibitors with Enhanced Antibacterial Activity and Reduced hERG Inhibition. ACS Infect Dis. 2019 Jul 12;5(7):1115-1128. doi: 10.1021/acsinfecdis.8b00375. Epub 2019 May 9. PMID: 31041863.
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 1;28(14):2477-2480. doi: 10.1016/j.bmcl.2018.06.003. Epub 2018 Jun 1. PMID: 29871847.
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 May 15;26(9):2354-2364. doi: 10.1016/j.bmc.2018.03.033. Epub 2018 Mar 23. PMID: 29656990; PMCID: PMC5962029.
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 is a Determinant of Etoposide Resistance in K562 Leukemia Cells via Heterodimerization with Isoform. Mol Pharmacol. 2018 May;93(5):515-525. doi: 10.1124/mol.117.111567. Epub 2018 Mar 7. PMID: 29514855.
Karmahapatra S, Kientz C, Shetty S, Yalowich JC, Rakotondraibe LH. Capsicodendrin from Cinnamosma fragrans Exhibits Antiproliferative and Cytotoxic Activity in Human Leukemia Cells: Modulation by Glutathione. J Nat Prod. 2018 Mar 23;81(3):625-629. doi: 10.1021/acs.jnatprod.7b00887. Epub 2018 Feb 6. PMID: 29406734.