Frank J. Rauscher III, Ph.D.

Title
Professor, Deputy Director
Department
The Wistar Institute
Institution
Wistar Institute of Anatomy and Biology
Address
3601 Spruce Street
City, State, Zip
Philadelphia, PA 19104
Phone
(215) 898-0995
E-mail
rauscher[at]wistar.org
Website
http://www.wistar.org/our-science/scientists/frank-j-rauscher-iii-phd
Research Field
Molecular Biology
Award Year
1991

Research

Research in the lab has been focusing on proteins such as HP1 that directly recognize modified histone tails and lead to gene silencing. HP1 recognizes histone H3 that is modified by methylation at Lysine 9 and this is required for gene silencing. HP1 expression is lost during the progression of breast cancers to metastatic potential. Reversing HP1 mediated gene silencing must be overcome in order to re-program gene expression in both cancer and normal cells. The lab has been interested in how this can be accomplished in mammalian stem cells and in cancer stem cells. Heterochromatin protein 1 (HP1) in Drosophila is required for stable epigenetic gene silencing classically observed as position effect variegation of a transgene integrated adjacent to constitutive heterochromatin. However, mammalian HP1 proteins may be euchromatic, can be deposited on active genes by specific corepressors and anchored there by histone H3 containing the lysine 9-methylation mark. Little is known about the physical properties of chromatin that contains euchromatic genes that are silenced via HP1 recruitment. Another project on cancer-related gene silencing concerns the SNAIL zinc-finger proteins that repress E-Cadherin (and other genes) during the Epithelial-Mesenchymal Transition (EMT) de-differentiation pathway, which occurs during metastatic progression. The lab cloned and characterized a novel co-repressor for the SNAIL and showed that it is required for E-Cadherin repression. The protein is a novel member of the LIM domain family and exists both in the cytoplasm and the nucleus. Current studies are underway to define the genomic binding sites and associated proteins. To this end the lab recently discovered that the LIM protein associates directly with an enzyme, which displays arginine, methyltransferase activity and that this enzyme is required for silencing.