Lori Wallrath, PhD

Portrait
Professor of Biochemistry

Contact Information

Primary Office
3136 MERF
Iowa City, IA 52242
319-335-7920

Education

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

Education/Training Program Affiliations

Department of Biochemistry PhD, Interdisciplinary Graduate Program in Genetics, Interdisciplinary Graduate Program in Molecular Medicine, Interdisciplinary Graduate Program in Translational Biomedicine, Medical Scientist Training Program

Research Summary

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.

Publications

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. PMID: 27110666.

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. PMID: 26795490.

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. PMID: 25830653.

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. PMID: 25996830.

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. PMID: 24415761.

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. PMID: 23839987.

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. PMID: 23427149.

Wallrath, L. L., Elgin, S. C. (2012). Enforcing silencing: dynamic HP1 complexes in Neurospora. Nature structural & molecular biology, 19(5), 465-7. PMID: 22551706.

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. PMID: 22186027.

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. PMID: 21450447.

Wallrath, L., Vitalini, M. & Elgin, S. (2014). Heterochromatin: A critical part of the genome. J. Workman (Eds.) pp. 529-552. Chromatin, Chapter 14, Springer Publishing.

Barton, L. J., Pinto, B. S., Wallrath, L. L. & Geyer, P. K. (2013). The Drosophila nuclear lamina protein otefin is required for germline stem cell survival. Developmental cell, 25(6), 645-54. PMID: 23806619.

Gilbert, D. M., Wallrath, L. L. (2011). Chromatin and chromosomes. Molecular biology of the cell, 22(6), 717. PMID: 21406580.

Cryderman, D. E., Vitalini, M. W. & Wallrath, L. L. (2011). Heterochromatin protein 1a is required for an open chromatin structure. (Vols. 2). (2), pp. 95-99. Transcription. PMID: 21468237.

Dialynas, G., Speese, S., Budnik, V., Geyer, P. K. & Wallrath, L. L. (2010). The role of Drosophila Lamin C in muscle function and gene expression. (Vols. 137). (18), pp. 3067-77. Development (Cambridge, England). PMID: 20702563.

Hines, K. A., Cryderman, D. E., Flannery, K. M., Yang, H., Vitalini, M. W., Hazelrigg, T., Mizzen, C. A. & Wallrath, L. L. (2009). Domains of heterochromatin protein 1 required for Drosophila melanogaster heterochromatin spreading. (Vols. 182). (4), pp. 967-77. Genetics. PMID: 19487560.

Schulze, S. R., Curio-Penny, B., Speese, S., Dialynas, G., Cryderman, D. E., McDonough, C. W., Nalbant, D., Petersen, M., Budnik, V., Geyer, P. K. & Wallrath, L. L. (2009). A comparative study of Drosophila and human A-type lamins. (Vols. 4). (10), pp. e7564. PloS one. PMID: 19855837.

Wallrath, L. L., Nagy, P. L. & Geyer, P. K. (2008). Epigenetics of development and human disease. (Vols. 647). (2-Jan) Mutation research. PMID: 18983859.

Dialynas, G. K., Vitalini, M. W. & Wallrath, L. L. (2008). Linking Heterochromatin Protein 1 (HP1) to cancer progression. Mutation research, 647(2-Jan), 13-20. PMID: 18926834.

Wallrath, L. L., Elgin, S. C. (2008). Stimulating conversations between HP1a and histone demethylase dKDM4A. Molecular cell, 32(5), 601-2. PMID: 19061634.

Pinto, B. S., Wilmington, S. R., Hornick, E. E., Wallrath, L. L. & Geyer, P. K. (2008). Tissue-specific defects are caused by loss of the Drosophila MAN1 LEM domain protein. (Vols. 180). (1), pp. 133-45. Genetics. PMID: 18723885.

Yang, H., Pesavento, J. J., Starnes, T. W., Cryderman, D. E., Wallrath, L. L., Kelleher, N. L. & Mizzen, C. A. (2008). Preferential dimethylation of histone H4 lysine 20 by Suv4-20. (Vols. 283). (18), pp. 12085-92. The Journal of biological chemistry. PMID: 18296440.

Wallrath, L. L., Elgin, S. C. (2008). Stimulating conversations between HP1aand histone demethylase dKDM4A. Cell.

Moss, T. J., Wallrath, L. L. (2007). Connections between epigenetic gene silencing and human disease. Mutation research, 618(2-Jan), 163-74. PMID: 17306846.

Moss, T. J., Wallrath, L. L. (2007). Diverse roles of HP1-Hsalpha in chromatindynamics, transcriptional regulation and breast cancer metastasis. Developments in Metastasis.

Schulze, S. R., Wallrath, L. L. (2007). Genome regulation by chromatin structure: paradigms established in Drosophila melanogaster. Annual review of entomology, 52, 171-92. PMID: 16881818.

Norwood, L. E., Moss, T. J., Margaryan, N. V., Cook, S. L., Wright, L., Seftor, E. A., Hendrix, M. J., Kirschmann, D. A. & Wallrath, L. L. (2006). A requirement for dimerization of HP1Hsalpha in suppression of breast cancer invasion. (Vols. 281). (27), pp. 18668-76. The Journal of biological chemistry. PMID: 16648629.

Wallrath, L. L., Geyer, P. K. (2006). TFIIIC boxes in the genome. Cell, 125(5), 829-31. PMID: 16751090.

Lomberk, G., Wallrath, L. & Urrutia, R. (2006). The Heterochromatin Protein 1 family. Genome biology, 7(7), 228. PMID: 17224041.

Schulze, S. R., Curio-Penny, B., Li, Y., Imani, R. A., Rydberg, L., Geyer, P. K. & Wallrath, L. L. (2005). Molecular genetic analysis of the nested Drosophila melanogaster lamin C gene. (Vols. 171). (1), pp. 185-96. Genetics. PMID: 15965247.

Cryderman, D. E., Grade, S. K., Li, Y., Fanti, L., Pimpinelli, S. & Wallrath, L. L. (2005). Role of Drosophila HP1 in euchromatic gene expression. (Vols. 232). (3), pp. 767-74. Developmental dynamics : an official publication of the American Association of Anatomists. PMID: 15704177.

Danzer, J. R., Wallrath, L. L. (2004). Mechanisms of HP1-mediated gene silencing in Drosophila. (Vols. 131). (15), pp. 3571-80. Development (Cambridge, England). PMID: 15215206.

Norwood, L. E., Grade, S. K., Cryderman, D. E., Hines, K. A., Furiasse, N., Toro, R., Li, Y., Dhasarathy, A., Kladde, M. P., Hendrix, M. J., Kirschmann, D. A. & Wallrath, L. L. (2004). Conserved properties of HP1(Hsalpha). (Vols. 336). (1), pp. 37-46. Gene. PMID: 15225874.

Norwood, L. E., Hines, K. A. & Wallrath, L. L. (2004). Deciphering the code ofsilence: Mechanisms of gene repression with connections to human disease. ChemTracts, 17, 308-324.

Stephens, G. E., Craig, C. A., Li, Y., Wallrath, L. L. & Elgin, S. C. (2004). Immunofluorescent staining of polytene chromosomes: exploiting genetic tools. pp. 372-93. Methods in enzymology. PMID: 14975319.

Wallrath, L. L., Danzer, J. R., Yazgan, O. & Geyer, P. K. (2004). Nuclear zones: amechanism for regulating gene expression by organizing the nucleus. Encyclopedia Biol. Chem, 3, 105-108.

Li, Y., Danzer, J. R., Alvarez, P., Belmont, A. S. & Wallrath, L. L. (2003). Effects of tethering HP1 to euchromatic regions of the Drosophila genome. (Vols. 130). (9), pp. 1817-24. Development (Cambridge, England). PMID: 12642487.

Eissenberg, J. C., Wallrath, L. L. (2003). Heterochromatin, position effects, and the genetic dissection of chromatin. Progress in nucleic acid research and molecular biology, 74, 275-99. PMID: 14510079.

Parnell, T. J., Grade, S. K., Geyer, P. K. & Wallrath, L. L. (2003). Position-effect variegation in human genetic disease. Encyclopedia of the Human Genome.

Li, Y., Kirschmann, D. A. & Wallrath, L. L. (2002). Does heterochromatin protein 1 always follow code?. (Vols. 99 Suppl 4). pp. 16462-9. Proceedings of the National Academy of Sciences of the United States of America. PMID: 12151603.

Kirschmann, D. A., Lininger, R. A., Gardner, L., Sefton, E. A., Odero, V. A., Ainsztein, A. M., Earnshaw, W. C., Wallrath, L. L. & Hendrix, M. (2000). Down-regulation of HP1Hsa expression is associated with the metastatic phenotype in breast cancer. (Vols. 60). pp. 3359-3363. Cancer Res.

Wallrath, L. L. (2000). Drosophila telomeric transgenes provide insights onmechanisms of gene silencing. Genetica, 109, 25-33. PMID: 11293791.

Henikoff, S., Eissenberg, J. C., Hilliker, A. J., Schmidt, E. R. & Wallrath, L. L. (2000). Reaching for new heitz. Genetica, 109, 7-8.

Sun, F. L., Cuaycong, M. H., Craig, C. A., Wallrath, L. L., Locke, J. & Elgin, S. (2000). The fourth chromosome of Drosophila melanogaster: Interspersedeuchromatic and heterochromatic domains. (Vols. 97). pp. 5340-5345. Proc. Natl. Sci USA.

Cryderman, D. E., Tang, H., Bell, C., Gilmour, D. S. & Wallrath, L. L. (1999). Heterochromatic silencing of Drosophila heat shock genes acts at the level of promoter potentiation. (Vols. 27). pp. 3364-3370. Nuc. Acids Res.

Cryderman, D. E., Morris, E. J., Biessmann, H., Elgin, S. & Wallrath, L. L. (1999). Silencing at Drosophila telomeres: nuclear organization and chromatinstructure play critical roles. (Vols. 18). pp. 3724-3735. EMBO J.

Cartwright, I. L., Cryderman, D. E., Gilmour, D. S., Pile, L. A., Wallrath, L. L., Weber, J. A. & Elgin, S. (1998). Analysis of Drosophila chromatin structurein vivo. pp. 462-496. Methods Enzymology.

Cryderman, D. E., Cuaycong, M. H., Elgin, S. & Wallrath, L. L. (1998). Characterization of sequences associated with position effect variegation atpericentric sites in Drosophila heterochromatin. (Vols. 107). pp. 277-285. Chromosoma.

Wallrath, L. L., Swede, M. J. & Elgin, S. (1998). Mapping chromatinstructure in Drosophila. pp. 59-77. Practical Approach: Chromatin.

Wallrath, L. L. (1998). Unfolding the mysteries of heterochromatin. Curr. Opin. Genet. Dev, 8, 147-153. PMID: 9610404.

Wallrath, L. L., Guntur, V. P., Rosman, L. E. & Elgin, S. (1996). DNArepresentation of variegating heterochromatic P-element inserts in diploid and polytene tissue of Drosophila melanogaster. (Vols. 104). pp. 519-527. Chromosoma.

Wallrath, L. L., Elgin, S. C. (1995). Position effect variegation in Drosophilais associated with an altered chromatin structure. (Vols. 9). pp. 1263-1277. Genes Dev.

Lu, Q., Wallrath, L. L. & Elgin, S. (1995). The role of the nucleosome of thehsp26 promoter. (Vols. 14). pp. 4738-4746. EMBO J.

Wallrath, L. L., Lu, Q., Granok, H. & Elgin, S. (1994). Architecturalvariations of inducible eukaryotic promoters: present and remodeling chromatinstructures. BioEssays, 16, 1-6. PMID: 8166669.

Lu, Q., Wallrath, L. L., Emanuel, P. A., Elgin, S. & Gilmour, D. S. (1994). Insensitivity of the preset hsp26 chromatin structure to a TATA box mutation inDrosophila. (Vols. 269). pp. 15906-15911. J. Biol. Gehm.

Lu, Q., Wallrath, L. L. & Elgin, S. (1994). Nucleosome positioning and generegulation. J. Cell. Biochem, 55, 83-92. PMID: 8083303.

Lu, Q., Wallrath, L. L., Granok, H. & Elgin, S. (1993). Distinct roles of(CT)n.(GA)n repeats and heat shock elements in chromatin structure andtranscriptional activation of the Drosophila hsp26 gene. (Vols. 13). pp. 2802-2814. Mol. Cell. Biol.

Shaffer, C. D., Wallrath, L. L. & Elgin, S. (1993). Regulating genes bypackaging domains: bits of heterochromatin in euchromatin?. Trends Genet, 9, 35-37. PMID: 8456498.

Elgin, S., Granok, H., Lu, Q. & Wallrath, L. L. (1993). The role of chromatinstructure in regulating gene expression: the hsp26 gene of Drosophilamelanogaster. Cold Spring Harbor Symp. Quant. Bio, LVII, 83-86. PMID: 7956096.

Lu, Q., Wallrath, L. L. & Elgin, S. (1993). Using Drosophila P-elementmediated germline transformation to examine the chromatin structure and expression of in vitro modified genes. pp. 333-357. Methods in Molecular Genetics.

Lu, Q., Wallrath, L. L., Allan, B. D., Glaser, R. L., Lis, J. T. & Elgin, S. (1992). A promoter sequence containing (CT)n.(GA)n repeats is critical for the formation ofthe DNase I hypersensitive sites in the Drosophila hsp26 gene. (Vols. 225). pp. 985-998. J. Mol. Biol.

Wallrath, L. L., Friedman, T. B. (1992). Combinative oligonucleotide-directeddeletions as a strategy for surveying the regulatory region of a gene. (Vols. 12). pp. 214-216. Biotechniques.

Friedman, T. B., Burnett, J. B., Lootens, J. B., Steinman, R. & Wallrath, L. L. (1992). The urate oxidase gene of Drosophila pseudoobscura and Drosophila melanogaster: evolutionary changes of sequence and regulation. (Vols. 34). pp. 62-77. J. Mol. Evol.

Wallrath, L. L., Friedman, T. B. (1991). Species differences in the temporalpattern of Drosophila UO expression are attributed to trans-acting regulatory changes. (Vols. 88). pp. 5489-5493. Proc. Natl. Acad. Sci USA.

Wallrath, L. L., Burnett, J. B. & Friedman, T. B. (1990). Molecularcharacterization of the Drosophila melanogaster urate oxidase gene: an ecdysonerepressiblegene expressed only in the Malpighian tubules. (Vols. 10). pp. 5114-5127. Mol. Cell. Biol.

Geyer, P. K., Wallrath, L. L. Heterochromatin: not just for silencing anymore: report of the Eighth International Conference on Drosophila Heterochromatin. Fly, 1(4), 251-6. PMID: 18820453.