Aaron Mehus

Role of Arsenic in the Development of Urothelial Cancer:

Arsenic is naturally occurring in groundwater and concentrations routinely exceed government standards in rural private wells. Urothelial cancer (UC) has the 4th highest incidence rate in men of all cancer types in North Dakota and there is a strong association between arsenic exposure and development of UC. Around 25% of diagnosed UC cases are muscle invasive (MIUC) which have poor prognosis and develop chemoresistance, especially if tumors are associated with squamous differentiation. Our lab has transformed normal urothelial cells (UROtsa) into tumorigenic cells by environmentally relevant exposures to arsenite (As3+). We have isolated several As3+-transformed UROtsa cell lines (As-T). These As-T cells all form subcutaneous tumors in immunocompromised mice that histologically resemble MIUC with squamous differentiation. My research is focused on gaining a better understanding of what drives squamous differentiation in MIUC with the ultimate goal in identifying less invasive diagnostics and more effective therapies for this cancer type.

1. Al-Marsoummi S, Mehus AA, Garrett SH, Sens DA, Somji S. The Effect of Retinoic Acid on Arsenite-Transformed Malignant UROtsa Bladder Cancer Cells: In Vitro Model of Basal Muscle-Invasive Bladder Cancer. Cancers. 2024; 16(6):1178. https://doi.org/10.3390/cancers16061178
2. Al-Marsoummi S, Mehus AA, Shrestha S, Rice R, Rossow B, Somji S, Garrett SH, Sens DA. Proteasomes Are Critical for Maintenance of CD133+CD24+ Kidney Progenitor Cells. International Journal of Molecular Sciences. 2023; 24(17):13303. https://doi.org/10.3390/ijms241713303
3. Mehus, A.A.; Jones, M.; Trahan, M.; Kinnunen, K.; Berwald, K.; Lindner, B.; Al-Marsoummi, S.; Zhou, X.D.; Garrett, S.H.; Sens, D.A.; Sens, M.A.; Somji, S. Pevonedistat Inhibits SOX2 Expression and Sphere Formation but Also Drives the Induction of Terminal Differentiation Markers and Apoptosis within Arsenite-Transformed Urothelial Cells. Int. J. Mol. Sci. 2023, 24, 9149. https://doi.org/10.3390/ijms24119149
4. Rust BM, Picklo MJ, Yan L, Mehus AA, Zeng H. Time-Restricted Feeding Modifies the Fecal Lipidome and the Gut Microbiota. Nutrients. 2023; 15(7):1562. https://doi.org/10.3390/nu15071562
5. Mehus AA, Bergum N, Knutson P, Shrestha S, Kalonick M, Zhou X, Garrett SH, Sens DA, Sens MA, Somji S. Chronic Arsenic Exposure Upregulates the Expression of Basal Transcriptional Factors and Increases Invasiveness of the Non-Muscle Invasive Papillary Bladder Cancer Line RT4. Int J Mol Sci. 2022 Oct 14;23(20):12313. doi: 10.3390/ijms232012313. PMID: 36293167; PMCID: PMC9604142.
6. Mehus AA, Rust B, Idso JP, Hanson B, Zeng H, Yan L, Bukowski MR, Picklo MJ. Time-restricted feeding mice a high-fat diet induces a unique lipidomic profile. J Nutr Biochem. 2021 Feb;88:108531. doi: 10.1016/j.jnutbio.2020.108531. Epub 2020 Oct 22. PMID: 33098972.
7. Blommel K, Knudsen CS, Wegner K, Shrestha S, Singhal SK, Mehus AA, Garrett SH, Singhal S, Zhou X, Voels B, Sens DA, Somji S. Meta-analysis of gene expression profiling reveals novel basal gene signatures in MCF-10A cells transformed with cadmium. Oncotarget. 2020 Sep 29;11(39):3601-3617. doi: 10.18632/oncotarget.27734. PMID: 33062196; PMCID: PMC7533076.
8. Mehus AA, Bergum N, Knutson P, Shrestha S, Zhou XD, Garrett SH, Sens DA, Sens MA, Somji S. Activation of PPARγ and inhibition of cell proliferation reduces key proteins associated with the basal subtype of bladder cancer in As3+-transformed UROtsa cells. PLoS One. 2020 Aug 21;15(8):e0237976. doi: 10.1371/journal.pone.0237976. PMID: 32822399; PMCID: PMC7444546.
9. Lin Yan, Sneha Sundaram, Aaron A. Mehus, Matthew J. Picklo. Time-restricted feeding attenuates high-fat diet-enhanced spontaneous metastasis of Lewis lung carcinoma in mice. Anticancer Res. 2019 Apr;39(4):1739-1748. doi: 10.21873/anticanres.13280.
10. Aaron A. Mehus, Aaron M. Dickey, Timothy P.L. Smith, Kathleen M. Yeater, and Matthew J. Picklo. Next-Generation Sequencing Identifies Polyunsaturated Fatty Acid Responsive Genes in the Juvenile Rat Cerebellum. Nutrients. 2019 Feb 15;11(2). pii: E407. doi: 10.3390/nu11020407.
11. Petr Žá?ek, Aaron A. Mehus, LuAnn Johnson, Michael Bukowski, Susan Raatz, Joseph Idso, and Matthew Picklo. Dietary Saturated Fatty Acid Type Impacts Obesity-Induced Metabolic Dysfunction and Plasma Lipidomic Signatures in Mice. J Nutr Biochem. 2019 Feb;64:32-44. doi: 10.1016/j.jnutbio.2018.10.005. Epub 2018 Oct 21.
12. Sneha Sundaram, Petr Žá?ek, Michael Bukowski, Aaron Mehus, Lin Yan, Matthew Picklo. Lipidomic Impacts of an Obesogenic Diet Upon Lewis Lung Carcinoma in Mice. Front Oncol. 2018 May 11;8:134. doi: 10.3389/fonc.2018.00134. eCollection 2018.
13. Aaron A. Mehus and Matthew J. Picklo. Brain and Hepatic Mt mRNA Is Reduced in Response to Mild Energy Restriction and n-3 Polyunsaturated Fatty Acid Deficiency in Juvenile Rats. Nutrients. 2017 Oct 19;9(10). pii: E1145. doi: 10.3390/nu9101145. PMID: 29048374
14. Shabb JB, Muhonen WW, Mehus AA. Quantitation of Human Metallothionein Isoforms in Cells, Tissues, and Cerebrospinal Fluid by Mass Spectrometry. Methods Enzymol. 2017;586:413-431. doi: 10.1016/bs.mie.2016.11.004. Epub 2016 Dec 7.
15. Mehus AA, Anderson RH, Roux KJ. BioID Identification of Lamin-Associated Proteins. Methods Enzymol. 2016;569:3-22. doi: 10.1016/bs.mie.2015.08.008. Epub 2015 Sep 26. PMID: 26778550
16. Mehus AA, Reed RJ, Lee VST, Littau SR, Hu C, Lutz EA, Burgess JL. Comparison of Acute Health Effects from Exposures to Diesel and Biodiesel Fuel Emissions. Journal of Occupational and Environmental Medicine. 2015 Jul;57(7):705-12. doi: 10.1097/JOM.0000000000000473. PMID: 26147538.
17. Mehus AA, Muhonen WW, Garrett SH, Somji S, Sens MA, Sens DA, Shabb JB. Quantitation of Human Metallothionein Isoforms: A Family of Small, Highly Conserved, Cysteine-rich Proteins. Mol Cell Proteomics. 2014 Apr;13(4):1020-33. doi: 10.1074/mcp.M113.033373. Epub 2014 Feb 3.
18. Somji S, Cao L, Mehus A, Zhou XD, Sens MA, Dunlevy JR, Garrett SH, Zheng Y, Larson JL, Sens DA. Comparison of expression patterns of keratin 6, 7, 16, 17, and 19 within multiple independent isolates of As(+3)- and Cd (+2)-induced bladder cancer : keratin 6, 7, 16, 17, and 19 in bladder cancer. Cell Biol Toxicol. 2011 Dec;27(6):381-96. doi: 10.1007/s10565-010-9169-z. Epub 2011 Sep 17.
19. Somji S, Zhou XD, Mehus A, Sens MA, Garrett SH, Lutz KL, Dunlevy JR, Zheng Y, Sens DA. Variation of keratin 7 expression and other phenotypic characteristics of independent isolates of cadmium transformed human urothelial cells (UROtsa). Chem Res Toxicol. 2010 Feb 15;23(2):348-56.

B.S., Mayville State University, Biology

MS, University of North Dakota, Biochemistry and Molecular Biology

Ph.D., University of North Dakota, Biochemistry and Molecular Biology