Pictured (left to right): Sara Mayer (Genetics PhD student), Meg Ketterer (Research Associate), Lori Wallrath (PI), Sydney Walker (Biochemistry major, ICRU Fellow), Nick Shaw (Research Intern), Elana Burnholtz (Genetics PhD Rotation student), Ashley Goll (Biochemistry PhD rotation student), and Ben Hinz (Biomedical Engineering major, ICRU Fellow)
Not pictured: Jose Rios-Monterrosa (Medical student, Research Track)
Mutations in the human LMNA gene cause a collection of diseases called laminopathies, which includes muscular dystrophies, heart problems, adipose tissues disorders, and early onset aging syndromes. The LMNA gene encodes lamins, intermediate filaments that form a meshwork that lines the inner nuclear membrane. Lamins provide structural support for the nucleus and play roles in genome organization, gene expression, and DNA repair. The mechanisms by which mutant lamins cause disease phenotypes are not well understood and there are no therapies. Currently, members of the Wallrath laboratory are investigating the molecular basis of muscular dystrophies and have developed Drosophila (fruit fly) models, which provide ease of genetic and cytological analyses. Human muscle biopsy tissue is used to demonstrate disease relevance of the findings. Their studies have identified signaling pathways altered by mutant lamins, providing new avenues for potential therapies.
Earle, A., Kirby, T., Fedorchak, G., Isermann, P., Patel, J., Irubanti, S., Moore, S., Bonne, G., Wallrath, L. & Lammerding, J. (2020). Mutant lamins cause nuclear envelope rupture and DNA damage in skeletal muscle cells. Nature Materials, 19, 464-473. PMID: 31844279.
Bhide, S., Kalvakuri, S., Trujillo, A., Connor, M., Young, G., Cryderman, D., Chandran, S., Nikravesh, M., Wallrath, L. & Melkani, G. (2018). Increasing autophagy and blocking Nrf2 suppresses mutant lamin-induced heart defects and shortened life span. Aging Cell, 17(3), e12747. DOI: 10.1111/acel.12747.
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.
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