Department of Biochemistry
Iowa City, IA 52242-1109 USA
fax: (319) 335-9570
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Lori Wallrath, PhD
Lori Wallrath, Ph.D
Professor of Biochemistry
Carver College of Medicine
University of Iowa
375 Newton Rd, 3136 MERF
Iowa City, IA 52242
Phone: (319) 335-7920
Lab Phone: (319) 335-7916
Fax: (319) 384-4770
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 collaborates with DNA methyltransferase I (DNMT1) to silence tumor suppressor genes and transposable elements near centromeres. The Wallrath laboratory collaborates with the laboratories of Charles Brenner (Biochemistry) and Kai Tan (Internal Medicine) to determine the effects of DNMT1 inhibitors on the re-activation of tumor suppressor genes and the expression of transposable elements in human breast cancer cells.
Myopathic lamin mutations impair nuclear stability in cells and tissue and disrupt nucleo-cytoskeletal coupling.
Zwerger M, Jaalouk DE, Lombardi ML, Isermann P, Mauermann M, Dialynas G, Herrmann H, Wallrath LL, Lammerding J.
Hum Mol Genet. 2013 Mar 3.
LMNA variants cause cytoplasmic distribution of nuclear pore proteins in Drosophila and human muscle.
Dialynas G, Flannery KM, Zirbel LN, Nagy PL, Mathews KD, Moore SA, Wallrath LL.
Hum Mol Genet. 2012 Apr 1;21(7):1544-56. doi: 10.1093/hmg/ddr592. Epub 2011 Dec 20.
Cover Image (see inset)
Enforcing silencing: dynamic HP1 complexes in Neurospora.
Wallrath LL, Elgin SC.
Nat Struct Mol Biol. 2012 May 3;19(5):465-7. doi: 10.1038/nsmb.2291.
Nuclear organization: taking a position on gene expression.
Geyer PK, Vitalini MW, Wallrath LL.
Curr Opin Cell Biol. 2011 Jun;23(3):354-9. doi: 10.1016/j.ceb.2011.03.002. Epub 2011 Mar 28. Review.
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