University of Iowa
Department of Biochemistry
4-403 BSB
Iowa City, IA 52242-1109 USA phone: 877-846-8569
or 319-335-7932
fax: (319) 335-9570
biochem@uiowa.edu

Department of Biochemistry

Professor of Biochemistry, PhD

Lab Web Site

Office: 3136 MERF
Phone: (319) 335-7920
Fax: (319) 384-4770
lori-wallrath@uiowa.edu

Lori L. Wallrath
375 Newton Rd
Biochemistry/Univ. of Iowa
Iowa City, IA 52242

Research Interests

The research in our laboratory is centered on connections between gene regulation/chromatin structure and disease. In the nucleus, genomic DNA is packaged into chromatin. Our research efforts are directed towards Heterochromatin Protein 1 (HP1), an evolutionarily conserved protein that plays a role in chromatin packaging and gene silencing. We are using the fruit fly Drosophila melanogaster as a model organism to study the mechanisms of gene silencing by HP1. Our results demonstrate that association of HP1 to a genomic site is sufficient to nucleate silent chromatin and cause alterations in chromatin structure.

We are also investigating the role of human HP1 in breast cancer invasion/metastasis through collaboration with Dr. Dawn Kirschmann of the Dr. Mary Hendrix laboratory (Northwestern University). HP1 is significantly down-regulated in highly/invasive metastatic breast cancer cells, compared with poorly invasive/non-metastatic breast cancer cells. Experiments are underway to identify genes regulated by HP1 and proteins that interact with HP1 in breast cancer cells. These data will shed light on the role of HP1 as a breast cancer metastatsis suppressor.

Figure 1. HP1 localization in the nucleus of a salivary gland cell.

In collaboration with the laboratory of Dr. Pamela Geyer (Department of Biochemistry, University of Iowa) we are studying the role of nuclear envelope proteins in gene regulation. In humans, mutations in Lamin A/C (encoding a nuclear envelope associated protein) give rise to diseases known as laminopathies, which include Emery Dreifuss muscular dystrophy, cardiomopathy and progeria (early onset aging). Most laminopathies have tissue-specific disease phenotypes, yet mutant Lamin A/C is expressed in almost all cells. Using tissue-specific expression tools available exclusively in Drosophila, we are determining the molecular basis of phenotypes associated with laminopathies.

Recent Publications

Moss, T.J. and Wallrath, L.L. (2007) Connections between epigenetic gene silencing and disease. Mutation Research 618:163-174.

Schulze, S.R., and Wallrath, L.L. (2007) Gene regulation by chromatin structure: Paradigms established in Drosophila melanogaster. Annu. Rev. Entomol. 52:171-192.

Wallrath, L.L., and Geyer, P.K. (2006) TFIIIC in the genome. Cell 125:829-831.

Norwood, L.E., Moss, T.J., Margaryan, N., Cook, S.L., Wright, L., Seftor, E.A., Hendrix, M.J.C., Kirschmann, D.A., and Wallrath, L.L. (2006) A requirement for dimerization of HP1 Hsa in suppression of breast cancer invasion. J. Biol. Chem. 281:18668-18676.

Schulze, S.R., Curio-Penny, B., Li, Y., Imani, R.A., Rydberg, L., Geyer, P.K., and Wallrath, L.L. (2005) Molecular genetic analysis of the nested Drosophila melanogaster Lamin C gene. Genetics 171:185-196.

Norwood, L.E., Hines, K.A., and Wallrath, L.L. (2005) Deciphering the code of silence: Mechanisms of gene repression with connections to human disease. Chemtracts-Biochemistry and Molecular Biology 17:308-324.

Cryderman, D.E., Grade, S.K., Li, Y., Fanti, L., Pimpinelli, S., and Wallrath, L.L. (2005) Role of Drosophila HP1 in euchromatic gene expression. Dev. Dyn. 232:767-774.

Stephens, G.E., Craig, C.A., Li, Y., Wallrath, L.L., and Elgin, S.C. (2004) Immunoflluorescent staining of polytene chromosomes: exploiting genetic tools. Methods Enzymol. 376:372-393.

Wallrath, L.L., Danzer, J.R., Yazgan, O. and P.K. Geyer (2004) Nuclear organization, chromatin structure and gene silencing, In Encyclopedia of Biological Chemistry (W.J. Lennarz & M.D. Lane, eds), Elsevier, Oxford, Vol 3: pp. 105-108.

Danzer, J.R., and Wallrath, L.L. (2004) Mechanisms of HP1-mediated gene silencing in Drosophila. Development 131:3571-3580.

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., and Wallrath, L.L. (2004) Conserved properties of HP1 (Hsalpha). Gene 336:37-46.

Parnell, T.J., Grade, S.K., Geyer, P.K. and Wallrath, L.L. (2003). Position-effect variegation in human genetic disease, in Cooper D (Ed.), Encyclopedia of the Human Genome. John Wiley & Sons, Ltd, p. 642-646 (Volume 4).

Eissenberg, J.C., and Wallrath, L.L. (2003) Heterochromatin, position effects, and the genetic dissection of chromatin. Prog. Nucleic Acid Res. Mol. Biol. 74:275-299.

Li, Y, Kirschmann, D.A. and Wallrath, L.L. (2002) Does heterochromatin protein 1 always follow code? Proc. Natl. Acad. USA 99:16462-16469.

Affiliations

Biochemistry Department
Molecular and Cellular Biology Program