Research Interests

Research Interests

HEALTH IMPACTS OF WILDFIRE SMOKE

The incidence and severity of wildfires are increasing due to climate change, and with them emerging threats to the population, both in the United States and worldwide. To be able to prepare and mitigate these threats we need a better understanding of the ramifications of wildfires. In addition to the fire itself, wildfires produces emission, that can affect an area >1000 times the burn extent, with potential far-reaching impacts on human health, the ecology, and economy. Wildfire emissions contain both particles, and gases that initiate many adverse reactions, such as genetic damage and inflammation. Our laboratory works at studying the cellular interactions with wildfire smoke that underlie disease effects, particularly cancer.

 

HUNTINGTON’S DISEASE

Huntington’s Disease (HD) is one of the longest studied hereditary diseases. The cause has long been known, it has been tracked down to an inherited defect in a single gene (huntingtin). There is also a good understanding of the process leading to this genetic mutation (trinucleotide repeat expansion), from work in the laboratories of Dr. C. McMurray and others. But how this mutated gene leads to the progressive breakdown of nerve cells in the brain is yet to be understood. In our study of the progression of HD, we have recently focused on metabolic effects that HD has in the brain. This altered metabolism has consequences on the oxidative load generated in the brain and might be an important link to neurodegeneration. This work has lead to our interest in one of the non-neuronal helper cells in the brain (the astrocytes), due to their important role in brain metabolism.

GENETIC DAMAGE

The genome codes the template for life, it stores this vast amount of information in strings of DNA. There are many intricate pathways that maintain the integrity of this information and repair DNA that is damaged. These pathways are a major area of scientific study. We are trying to develop tools to help elucidate the pathways that are activated after damage and understand the implications to the genome. These tools would allow us to target DNA damage (oxidation) to a single genetic site and pick out what proteins are part of the response.

INFRARED SPECTROSCOPY FOR BIO-IMAGING

The chemical features common to molecules in living cells have vibrational energies that are within the Infrared (IR) energy range and every biomolecule in a cell has a distinct absorption spectrum in the IR region. This means that if you could image a living cell across the IR spectrum you would, in theory, have a compilation reading of all it’s biomolecules, or a reading of the state of the cell. We are trying to develop and validate IR microscopy of cells and tissue, as a tool that could be used for the characterization of disease.

 

Selected Publications:

1.Polyzos, A. A., Cheong, A., Yoo, J. H., Blagec, L., Toprani, S. M., Nagel, Z. D., & McMurray, C. T. (2024). Base excision repair and double strand break repair cooperate to modulate the formation of unrepaired double strand breaks in mouse brain. Nat Commun, 15(1), 7726. doi:10.1038/s41467-024-51906-5

2.Laverde, E. E., Polyzos, A. A., Tsegay, P. P., Shaver, M., Hutcheson, J. D., Balakrishnan, L., . . . Liu, Y. (2022). Flap Endonuclease 1 Endonucleolytically Processes RNA to Resolve R-Loops through DNA Base Excision Repair. Genes (Basel), 14(1). doi:10.3390/genes14010098

3.Lovergne L, Ghosh D, Schuck R, Polyzos AA, Chen AD, Martin MC, Barnard ES, Brown JB, McMurray CT. An infrared spectral biomarker accurately predicts neurodegenerative disease class in the absence of overt symptoms. Sci Rep. 2021;11(1):15598. doi: 10.1038/s41598-021-93686-8. PubMed PMID: 34341363.

4.Wipf, P., Polyzos, A. A., & McMurray, C. T. (2021). A Double-Pronged Sword: XJB-5-131 Is a Suppressor of Somatic Instability and Toxicity in Huntington’s Disease. J Huntingtons Dis. doi:10.3233/JHD-210510

5.Polyzos AA, Lee DY, Datta R, Hauser M, Budworth H, Holt A, Mihalik S, Goldschmidt P, Frankel K, Trego K, Bennett MJ, Vockley J, Xu K, Gratton E, McMurray CT. Metabolic Reprogramming in Astrocytes Distinguishes Region-Specific Neuronal Susceptibility in Huntington Mice. Cell Metab. 2019;29(6):1258-73 e11. doi: 10.1016/j.cmet.2019.03.004. PubMed PMID: 30930170; PMCID: PMC6583797.

6.Polyzos AA, Wood NI, Williams P, Wipf P, Morton AJ, McMurray CT. XJB-5-131-mediated improvement in physiology and behaviour of the R6/2 mouse model of Huntington’s disease is age- and sex- dependent. PLoS One. 2018;13(4):e0194580. doi: 10.1371/journal.pone.0194580. PubMed PMID: 29630611.

7.Baumgartner A, Ferlatte Hartshorne C, Polyzos AA, Weier HG, Weier JF, O’Brien B. Full Karyotype Interphase Cell Analysis. J Histochem Cytochem. 2018:22155418771613. doi: 10.1369/0022155418771613. PubMed PMID: 29672206.

8.Polyzos AA, McMurray CT. Close encounters: Moving along bumps, breaks, and bubbles on expanded trinucleotide tracts. DNA Repair (Amst). 2017;56:144-55. doi: 10.1016/j.dnarep.2017.06.017. PubMed PMID: 28690053; PMCID: PMC5558859.

9.Polyzos AA, McMurray CT. The chicken or the egg: mitochondrial dysfunction as a cause or consequence of toxicity in Huntington’s disease. Mech Ageing Dev. 2016. doi: 10.1016/j.mad.2016.09.003. PubMed PMID: 27634555.

10.Polyzos A, Holt A, Brown C, Cosme C, Wipf P, Gomez-Marin A, Castro MR, Ayala-Pena S, McMurray CT. Mitochondrial targeting of XJB-5-131 attenuates or improves pathophysiology in HdhQ150 animals with well-developed disease phenotypes. Hum Mol Genet. 2016;25(9):1792-802. doi: 10.1093/hmg/ddw051. PubMed PMID: 26908614; PMCID: PMC4986333.

11.Weier JF, Hartshorne C, Nguyen HN, Baumgartner A, Polyzos AA, Lemke KH, Zeng H, Weier HU. Analysis of human invasive cytotrophoblasts using multicolor fluorescence in situ hybridization. Methods. 2013;64(2):160-8. doi: 10.1016/j.ymeth.2013.05.021. PubMed PMID: 23748112.

12.Park CC, Georgescu W, Polyzos A, Pham C, Ahmed KM, Zhang H, Costes SV. Rapid and automated multidimensional fluorescence microscopy profiling of 3D human breast cultures. Integr Biol (Camb). 2013;5(4):681-91. doi: 10.1039/c3ib20275e. PubMed PMID: 23407655; PMCID: PMC3641787.

13.O’Brien B, Zeng H, Polyzos AA, Lemke KH, Weier JF, Wang M, Zitzelsberger HF, Weier HU. Bioinformatics tools allow targeted selection of chromosome enumeration probes and aneuploidy detection. J Histochem Cytochem. 2013;61(2):134-47. doi: 10.1369/0022155412470955. PubMed PMID: 23204113; PMCID: PMC3636690.

14.Zeng H, Weier JF, Wang M, Kassabian HJ, Polyzos AA, Baumgartner A, O’Brien B, Weier HU. Bioinformatic Tools Identify Chromosome-Specific DNA Probes and Facilitate Risk Assessment by Detecting Aneusomies in Extra-embryonic Tissues. Curr Genomics. 2012;13(6):438-45. doi: 10.2174/138920212802510510. PubMed PMID: 23450259; PMCID: PMC3426778.

15.Neumaier T, Swenson J, Pham C, Polyzos A, Lo AT, Yang P, Dyball J, Asaithamby A, Chen DJ, Bissell MJ, Thalhammer S, Costes SV. Evidence for formation of DNA repair centers and dose-response nonlinearity in human cells. Proc Natl Acad Sci U S A. 2012;109(2):443-8. doi: 10.1073/pnas.1117849108. PubMed PMID: 22184222; PMCID: PMC3258602.

16.Hsu JH, Zeng H, Lemke KH, Polyzos AA, Weier JF, Wang M, Lawin-O’Brien AR, Weier HU, O’Brien B. Chromosome-specific DNA repeats: rapid identification in silico and validation using fluorescence in situ hybridization. Int J Mol Sci. 2012;14(1):57-71. doi: 10.3390/ijms14010057. PubMed PMID: 23344021; PMCID: PMC3565251.

17.Tang J, Enderling H, Becker-Weimann S, Pham C, Polyzos A, Chen CY, Costes SV. Phenotypic transition maps of 3D breast acini obtained by imaging-guided agent-based modeling. Integr Biol (Camb). 2011;3(4):408-21. doi: 10.1039/c0ib00092b. PubMed PMID: 21373705; PMCID: PMC4009383.

18.Marchetti F, Rowan-Carroll A, Williams A, Polyzos A, Berndt-Weis ML, Yauk CL. Sidestream tobacco smoke is a male germ cell mutagen. Proc Natl Acad Sci U S A. 2011;108(31):12811-4. doi: 10.1073/pnas.1106896108. PubMed PMID: 21768363; PMCID: PMC3150936.

19.Chiolo I, Minoda A, Colmenares SU, Polyzos A, Costes SV, Karpen GH. Double-strand breaks in heterochromatin move outside of a dynamic HP1a domain to complete recombinational repair. Cell. 2011;144(5):732-44. doi: 10.1016/j.cell.2011.02.012. PubMed PMID: 21353298; PMCID: PMC3417143.

20.Polyzos, A., Schmid, T. E., Pina-Guzman, B., Quintanilla-Vega, B., & Marchetti, F. (2009). Differential sensitivity of male germ cells to mainstream and sidestream tobacco smoke in the mouse. Toxicol Appl Pharmacol, 237(3), 298-305. doi:10.1016/j.taap.2009.03.019

21.Leland S, Nagarajan P, Polyzos A, Thomas S, Samaan G, Donnell R, Marchetti F, Venkatachalam S. Heterozygosity for a Bub1 mutation causes female-specific germ cell aneuploidy in mice. Proc Natl Acad Sci U S A. 2009;106(31):12776-81. doi: 10.1073/pnas.0903075106. PubMed PMID: 19617567; PMCID: PMC2722367.

22.Yauk CL, Polyzos A, Rowan-Carroll A, Kortubash I, Williams A, Kovalchuk O. Tandem repeat mutation, global DNA methylation, and regulation of DNA methyltransferases in cultured mouse embryonic fibroblast cells chronically exposed to chemicals with different modes of action. Environ Mol Mutagen. 2008;49(1):26-35. doi: 10.1002/em.20359. PubMed PMID: 18172875.

23.Yauk C, Polyzos A, Rowan-Carroll A, Somers CM, Godschalk RW, Van Schooten FJ, Berndt ML, Pogribny IP, Koturbash I, Williams A, Douglas GR, Kovalchuk O. Germ-line mutations, DNA damage, and global hypermethylation in mice exposed to particulate air pollution in an urban/industrial location. Proc Natl Acad Sci U S A. 2008;105(2):605-10. doi: 10.1073/pnas.0705896105. PubMed PMID: 18195365; PMCID: PMC2206583.

24.Polyzos A, Parfett C, Healy C, Douglas GR, Yauk CL. Instability of expanded simple tandem repeats is induced in cell culture by a variety of agents: N-Nitroso-N-ethylurea, benzo(a)pyrene, etoposide and okadaic acid. Mutat Res. 2006;598(1-2):73-84. doi: 10.1016/j.mrfmmm.2006.01.016. PubMed PMID: 16516931.

25.Polyzos A, Parfett C, Healy C, Douglas G, Yauk C. A single-molecule PCR approach to the measurement of induced expanded simple tandem repeat instability in vitro. Mutat Res. 2006;594(1-2):93-100. doi: 10.1016/j.mrfmmm.2005.08.010. PubMed PMID: 16310811.

 

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