Biographical Sketch

Dr. Laimins received his BS degree in physics from Case Western Reserve University. He went on to the University of Chicago where in 1981 he obtained his PhD degree in biophysics and theoretical biology studying ion transport in bacteria. Dr. Laimins performed his postdoctoral work on gene expression at the National Cancer Institute under the direction of Dr. George Khoury. Dr. Laimins joined the faculty of Northwestern in 1994.

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Research Description

Molecular biology of human papillomaviruses (cervical cancer; viral pathogenesis; transformation; cell cycle progression; epithelial differentiation: gene expression)

Research Abstract

My laboratory studies the molecular biology of human papillomaviruses (HPV) and their association with cervical cancer. Our efforts are divided into two main categories. The first is examination of how the viral oncoproteins E6 and E7 contribute to the development of malignancy and the second is studies on the mechanisms controlling the viral life cycle in differentiating epithelia. More than 100 distinct types of human papillomavirus have been identified and approximately one-third specifically target squamous epithelial cells in the genital tract. Of these genital papillomaviruses, a subset including types 16,18 and 31 have been shown to be the etiological agents of most cervical cancers. One of our goals is to understand why infection by specific HPV types contributes to the development of malignancy. For these studies we have examined the interaction of the oncoproteins E6 and E7 with cellular proteins. In particular, E6 binds the p53 protein and facilitates its degradation by a ubiquitin-mediated pathway. It also activates telomerase as well as associates with PDZ-domain containing proteins. E7 binds the retinoblastoma gene product and alters its cell cycle regulatory properties. E7 also binds to histone deacetylases and modifies their functions. The interactions of the E6 and E7 proteins with these cellular proteins are being examined at both the biochemical and genetic level. Our second major area of study involves the examination of the papillomavirus life cycle. The production of papillomaviruses is closely linked to epithelial differentiation and progeny viruses are replicated in terminally differentiated epithelial cells. We have used organotypic tissue culture systems to faithfully reproduce the differentiation program of epithelial cells in the laboratory. Using this system, the viral life cycle has been duplicated.  We are studying the mechanisms that regulate viral DNA replication, cell entry, immune evasion and gene expression. These studies should provide insight into viral pathogenesis as well as the mechanisms regulating epithelial differentiation.

Publications

Longworth, M. and Laimins, L. A. The binding of histone deacetylases and the integrity of zinc finger-like motifs of the E7 protein are essential for the life cycle of human papillomavirus type 31 J. Virol.78: 3533-3541, 2004.

Lee, C. and L.A. Laimins The role of the PDZ domain-binding motif of the oncoprotein E6 in the productive life cycle of human papillomavirus type 31. J. Virol. 2004. 78: 12366-12377.2004.

Spink, K.M. and Laimins, L. A.  Induction of the human papillomavirus type 31 late promoter requires differentiation but not DNA amplification. .J.Virol. 2005. 79:4918-4926. 2005.

Wilson, R., Fehrmann, F.and Laimins L.A.  The role of the E1^E4 protein in the differentiation-dependent life cycle of human papillomavirus type 31.J.Virol. 79:6732-6740. 2005.