Wallrath, Lori - University of Iowa - Department of Biochemistry

个人简介

Education BS, Microbiology, Michigan State University PhD, Genetics, Michigan State University Post Doctoral Fellow, Chromatin Structure and Gene Expression, Washington University in St. Louis

研究领域

Research in the Wallrath laboratory is focused the role of chromatin packaging, gene expression and nuclear organization, with respect to human disease. The three dimensional organization of the genome within the nucleus is important for proper gene regulation. Lamins are intermediate filament proteins that line the inner side of the nuclear envelope providing structural support for the nucleus and regulating gene expression through connections made with chromatin. Mutations in lamins cause a collection of diseases called laminopathies that include musculear dystrophy, cardiomyopathy and early onset aging. It is unclear how mutant lamins cause disease. To address this issue, the laboratory has generated a Drosophila (fruit fly) model for muscle laminopathies. Flies expressing mutant lamins exhibit muscular dystrophy and die due to loss of muscle function. This model is currently being used to understand how mutant lamins misregulate genes and cause altered signaling in biological pathways. Eukaryotic genomes are packaged with histones and non-histone chromosomal proteins that collectively regulate gene expression. Heterochromatin Protein 1 (HP1) is a non-histone protein that collaboratorates with DNA methyltransferase I (DNMT1) to silence tumor suppressor genes. In collaboration with the laboratories of Charles Brenner (Biochemistry) and Kai Tan (Internal Medicine), experiments are underway to determine the effects of novel DNMT1 inhibitors on the re-activation of tumor suppressor genes in human breast cancer cells.

近期论文

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Wallrath, L. L., Bohnekamp, J. & Magin, T. M. (2016). Cross talk between the cytoplasm and nucleus during development and disease.. Current opinion in genetics & development, 37, 129-36. DOI: 10.1016/j.gde.2016.03.007. Bohnekamp, J., Cryderman, D. E., Thiemann, D. A., Magin, T. M. & Wallrath, L. L. (2016). Using Drosophila for Studies of Intermediate Filaments.. Methods in enzymology, 568, 707-26. DOI: 10.1016/bs.mie.2015.08.028. Dialynas, G., Shrestha, O. K., Ponce, J. M., Zwerger, M., Thiemann, D. A., Young, G. H., Moore, S. A., Yu, L., Lammerding, J. & Wallrath, L. L. (2015). Myopathic lamin mutations cause reductive stress and activate the nrf2/keap-1 pathway.. PLoS genetics, 11(5), e1005231. DOI: 10.1371/journal.pgen.1005231. Bohnekamp, J., Cryderman, D. E., Paululat, A., Baccam, G. C., Wallrath, L. L. & Magin, T. M. (2015). A Drosophila Model of Epidermolysis Bullosa Simplex.. The Journal of investigative dermatology, 135(8), 2031-9. DOI: 10.1038/jid.2015.129. Azzaz, A., Vitalini, M., Thomas, A., Price, J., Blacketer, M., Cryderman, D., Zirbel, L., Woodcock, C., Elcock, A., Wallrath, L. & Shogren-Knaak, M. (2014). Human heterochromatin protein 1a promotes nucleosome associations that drive chromatin condensation. J Biol Chem, 289(10), 6850-61. DOI: 10.1074/jbc.M113.512137. Zwerger, M., Jaalouk, D. E., Lombardi, M. L., Isermann, P., Mauermann, M., Dialynas, G., Herrmann, H., Wallrath, L. L. & Lammerding, J. (2013). Myopathic lamin mutations impair nuclear stability in cells and tissue and disrupt nucleo-cytoskeletal coupling. Human molecular genetics, 22(12), 2335-49. Fagan, R. L., Cryderman, D. E., Kopelovich, L., Wallrath, L. L. & Brenner, C. (2013). Laccaic Acid A is a Direct, DNA-Competitive Inhibitor of DNA Methyltransferase 1. The Journal of biological chemistry. Dialynas, G., Flannery, K. M., Zirbel, L. N., Nagy, P. L., Mathews, K. D., Moore, S. A. & Wallrath, L. L. (2012). LMNA variants cause cytoplasmic distribution of nuclear pore proteins in Drosophila and human muscle. (Vols. 21). (7), pp. 1544-56. Human molecular genetics. Wallrath, L. L., Elgin, S. C. (2012). Enforcing silencing: dynamic HP1 complexes in Neurospora. Nature structural & molecular biology, 19(5), 465-7. Geyer, P. K., Vitalini, M. W. & Wallrath, L. L. (2011). Nuclear organization: taking a position on gene expression. Current opinion in cell biology, 23(3), 354-9.