Richard A. Katz, PhD
Lab Phone: 215-728-3668
Our research focuses on the epigenetic control of gene expression. Epigenetics is the study of inherited changes in gene expression or cell phenotype that are independent of DNA sequence, but rather, are controlled by modifications to chromatin. The most dramatic example of epigenetic control is the specialization of cells that occurs during embryonic development and adult cell differentiation, whereby the DNA in each cell is largely identical, but specific genes sets are switched on or off. These on-off gene states are “memorized” through many cell divisions. Errors in this process can lead to a variety of diseases, including cancer. “Epigenetic gene silencing” refers to the heritable shut-off of genes. The two major mechanisms that underlie epigenetic silencing are DNA methylation and histone modifications, and hundreds of factors participate in initiating and maintaining these modifications on chromatin. Inappropriate gene silencing can lead to cancer and other diseases, but unlike gene inactivation due to mutations, epigenetic gene silencing is reversible. One goal of our research is to identify networks and novel cellular factors that maintain epigenetic gene silencing, such that new therapies can be devised to reactivate critical genes. Furthermore, as epigenetic mechanisms control cellular identity and plasticity, we are investigating strategies whereby cancer cells can be returned to a normal state.
The projects being carried out in our laboratory are aimed at identifying epigenetic silencing factor networks, and their relevance to cancer and other diseases. We are working in the following areas: 1. High throughput siRNA screening to identify silencing factor networks. 2. The role of the nuclear lamina in epigenetic control. 3. Epigenetic plasticity of cancer cells. 4. Epigenetic silencing as an antiviral response. 5. Dietary compounds that influence epigenetic processes.Description of research projects
- Poleshko, A., Mansfield, K.M., Burlingame, C.C., Andrake, M.D., Shah, N.R. *Katz, R.A. The human protein PRR14 tethers heterochromatin to the nuclear lamina during interphase and mitotic exit. Cell Reports, in press, 2013.
- Shalginskikh, N., Poleshko, A., Skalka, A.M., *Katz, R.A. Retroviral DNA methylation and epigenetic repression are mediated by the antiviral host protein Daxx. J. Virol. 87:2137-2150, 2013. (SPOTLIGHT Article of Significant Interest Selected by the Editors)
- Poleshko, A., Shalginskikh N., *Katz, R.A. Identification of epigenetic silencing factors by siRNA screening. Epigenomics: From Chromatin Biology to Therapeutics. Cambridge University Press, K Appasani, Editor., 2012.
- Poleshko, A., Einarson, M.B., Adams, P.D., Zhang, R., Skalka, A.M., *Katz. R.A. Identification of a functional network of human epigenetic silencing factors, J. Biol. Chem. 285:422-33, 2010.