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.
Myopathic lamin mutations cause reductive stress and activate the Nrf2/Keap-1 pathway.
Dialynas G, Shrestha OK, Ponce JM, Zwerger M, Thiemann DA, Young GH, Moore SA, Yu L, Lammerding J, Wallrath LL.
PLoS Genet. 2015 May 21;11(5):e1005231. doi: 10.1371/journal.pgen.1005231. eCollection 2015 May.
Human heterochromatin protein 1α promotes nucleosome associations that drive chromatin condensation.
Azzaz AM, Vitalini MW, Thomas AS, Price JP, Blacketer MJ, Cryderman DE, Zirbel LN, Woodcock CL, Elcock AH, Wallrath LL, Shogren-Knaak MA.
J Biol Chem. 2014 Mar 7;289(10):6850-61. doi: 10.1074/jbc.M113.512137. Epub 2014 Jan 10.
PMID: 24415761 Free PMC Article