Research Interests
Research Interests
The nucleus is “operations central” for eukaryotic cells. It houses genomic DNA and coordinates major cellular activities through the production of messenger RNA from DNA. The nucleus is surrounded by a nuclear envelope that provides security for the genomic DNA and regulates the flow of macromolecules to and from the cytoplasm. The Wallrath laboratory is researching mutations in genes encoding nuclear proteins that cause human disease. Curiously, these genes are expressed in all tissues of the body; however, the mutations cause tissue-specific defects. Mutations in the SNRNP200 gene can cause Retinitis Pigmentosa, a vision disorder that worsens with age. The SNRNP200 gene encodes an RNA helicase that is an essential component of the spliceosome, a large protein complex that removes introns and joins exons to make mature mRNAs. Mutations in the LMNA gene cause rare types of muscular dystrophy. The LMNA gene encodes lamins, filament-forming proteins that assemble into a meshwork on the inside of the nuclear envelope. The mechanisms by which mutations in these two genes cause disease and the identification of new targets for treatment are the focus of research.
Selected Publications
Mohar, M.P., Powers, B.A., Hinz, B., Bock, A.R., McCoy-Munger, H., Darr, Z., Shumaker, M.W., Wemmie, A.T., Saxena, A., and Wallrath, L.L. (2026) An unbiased drug screen in a Drosophila model of LMNA-muscular dystrophy identifies calcium channel blockers as potential treatments. Int. J. Mol. Sci. DOI: 10.3390/ijms27188367 PMCID: PMC13607455 PMID: 42794794
Mayer, S.K., Christensen, Q.H., McCoy-Munger, H., Mohar, N.P., Botero, V., Tomchik, S.M., Rong, Y., Drack, A.V., and Wallrath, L.L. (2026) N-acetyl cysteine alleviates retinal defects in Drosophila models of SNRNP200-associated retinitis pigmentosa. Hum. Mol. Genet. 35:ddag077. DOI: 10.1093/hmg/ddag077 PMCID: PMC13648025 PMID: 42593897
Mohar, N.P., Langland, C.J., Darr, Z., Viles, J., Moore, S.A., Darbro, B.W., Wallrath, L.L. (2025) A genetic variant in SMAD7 acts as a modifier of LMNA-associated muscular dystrophy, implicating SMAD signaling as a therapeutic target. Sci. Adv. 11:eads7903: DOI:10.1126/sciadv.ads7903 PMCID: PMC12007578 PMID: 40249815
Mohar, N.P., Cox, E.M., Adelizzi, E., Moore, S.A., Mathews, K.S., Darbro, B.W., and Wallrath, L.L. (2024) The influence of genetic variation in CCDC78 on LMNA-associated skeletal muscle disease. Int. J. Mol. Sci. 25(9):4930 DO1: 10.3390/ijms25094930 PMCID: PMC11084688 PMID: 38732148