MENU

Richard A. Katz, PhD

About

Professor

Adjunct Professor, 
Fels Institute for Cancer Research and Molecular Biology,
 Temple University School of Medicine

Research Program

Katz Lab, 2015
PRR14 tehers heterochromatin to the nuclear lamina through Heterochromatin Protein 1 (HP1)
PRR14 binds anaphase chromosomes through HP1

 

Education, Training & Credentials

Educational Background

  • PhD, Microbiology, Columbia University, College of Physicians and Surgeons, New York, NY, 1983
  • BS, Biology, Summa cum laude, Syracuse University, Syracuse, NY, 1975
Research Profile

Research Program

Research Interests

Epigenetic Regulation in Cancer and Normal Cells

  • The role of the nuclear lamina in epigenetic control.
  • High throughput siRNA screening to identify epigenetic silencing factor networks.
  • Epigenetic plasticity of melanoma cells.
  • Epigenetic silencing as an antiviral response.
  • Functional analyses of candidate breast cancer genes identified by Genome-wide Association Studies (GWAS) and Differential Allelic-Specific Expression (DASE). 

Lab Overview

Role of the nuclear lamina in epigenetic control

The nuclear lamina is a protein meshwork found under the inner nuclear membrane of metazoan cells. Defects in the nuclear lamina are associated with a variety of diseases, including cancer. One function of the nuclear lamina is to organize epigenetically silent genes and heterochromatin at the inner nuclear periphery. Our siRNA-based epigenetic screening approach has identified a previously unstudied human protein, PRR14, that functions to tether heterochromatin to the nuclear lamina. Furthermore, PRR14 assembles in stepwise manner at mitotic exit, first binding to heterochromatin on anaphase chromosomes, followed by re-association with the nuclear lamina. We have proposed that PRR14 may thereby guide the reattachment of heterochromatin. We are currently using a variety of methods to further elucidate the detailed mechanisms and mitotic dynamics of heterochromatin-nuclear lamina interactions.

Identification of epigenetic silencing factor networks 

(in collaboration with J.P. Issa, Cancer Epigenetics Program)

A genome-wide, gene-by-gene siRNA-based knockdown screen has been developed to identify novel factors and networks that maintain epigenetic gene silencing in human cells. A human reporter cell system was devised whereby reactivation of an epigenetically silent green fluorescent protein (GFP) gene provides a high throughput readout. Such screens have the potential to identify novel cellular pathways that mark chromatin for epigenetic silencing, and thus reveal new targets for epigenetic therapy of cancer and other diseases. Recent studies have focused on the detailed characterization of several novel epigenetic silencing factors identified through this approach.

Epigenetic plasticity of melanoma cells

(in collaboration with A. Bellacosa, Cancer Epigenetics Program)

A prominent feature of  melanoma  is phenotypic and functional cellular heterogeneity.  We developed a system to study melanoma cell plasticity in culture, whereby genes that drive this process can be identified.  The biological relevance of these factors is then  assessed in human melanoma tissues. We thereby can detect candidate factors that can serve as novel targets for therapy, or as biomarkers.  We recently identified the human ID4 protein as a mediator of plasticity, and it was found to be highly expressed in melanoma tissues.

Epigenetic silencing as an antiviral response

(in collaboration with A.M. Skalka, Blood Cell Development and Function)

Integrated retroviral DNA is subject to epigenetic silencing in human cells. We previously showed that the human Daxx protein is an antiviral factor that binds to the incoming retroviral DNA-protein complex, and acts as an adapter to recruit epigenetic silencing factors.  These results have important implications for how human cells can respond to foreign viral DNA.

Functional analyses of candidate breast cancer genes identified by Genome-Wide Association Studies (GWAS) and Differential Allelic-Specific Expression (DASE)

(in collaboration with X. Chen, Cancer Epigenetics Program).

As part of our collaborative effort to characterize factors encoded by novel breast cancer genes, we have implemented the BioID method to identify functional binding partners.  BioID detects candidate binding partners in live cells, and our initial data sets are highly informative.   

 

People

Valentina Medvedeva, MS

Graduate Student

Room: W422
215-728-3669

Trinity Pellegrin, BS

Scientific Technician I

Room: W422
215-728-3669

Alison Biester

FCCC High School Immersion Program, Germantown Friends School

Room: W422
215-728-3669

Adam Maynard

Undergraduate Summer Fellow, Rennsselaer Polytechnic Institute

Room: W422
215-728-3669

Jessica Goldshteyn

Drexel Post-Baccalaureate Student (Volunteer)

Room: W422
215-728-3669

Kelly Dunlevy

Student Assistant, Chestnut Hill College

Room: W422
215-728-3669

Jason Wasserman

Student Assistant, Chestnut Hill College

Room: W422
215-728-3669

Laboratory Alumni/ae

Caroline Burlingame
Laurie-Ann Davis
Rushaniya Fazliyeva
Katelyn M. Mansfield
Shayan Patel
Yuval Peretz, PhD
Andrey Poleshko, PhD
Neil Shah
Natalia Shalginskikh, PhD
Publications

Selected Publications

Peretz, Y., Wu, H., Patel, S., Bellacosa, A., Katz, R.A. Inhibitor of DNA Binding 4 (ID4) is highly expressed in human melanoma tissues and may function to restrict normal differentiation of melanoma cells. PLoS One 10:e0116839, 2015. PMCID: PMC4314081

Poleshko, A., Kossenkov, A.V., Shalginskikh, N., Pecherskaya, A., Einarson, M.B., Skalka, A.M., Katz, R.A. Human factors and pathways essential for mediating epigenetic gene silencing. Epigenetics 9:1280-1289, 2014.  Selected for Cover Art.  PMCID: PMC4169020

Poleshko, A., Katz, R.A. Specifying peripheral heterochromatin during nuclear lamina reassembly. Nucleus 5:32-39, 2014. PMCID: PMC4028353

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 Rep. 5:292-301, 2013. PMCID: PMC3867587

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.  Selected by the Editors as an "Article of Significant Interest".  PMCID: PMC3571491

Poleshko, A., Shalginskikh, N., Katz, R.A.*  Functional networks of human epigenetic factors.  In: Epigenomics: From Chromatin Biology to Therapeutics (Appasani, K., ed.),  pp. 30-46.  Cambridge University Press, 2012.

Poleshko, A., Einarson, M.B., Shalginskikh, N., Zhang, R., Adams, P.D., Skalka, A.M., Katz, R.A. Identification of a functional network of human epigenetic silencing factors. J. Biol. Chem. 285:422-433, 2010. PMCID: PMC2804189

Frescas, D., Guardavaccaro, D., Kuchay, S.M., Kato, H., Poleshko, A., Basrur, V., Elenitoba-Johnson, K.S., Katz, R.A., Pagano, M. KDM2A represses transcription of centromeric satellite repeats and maintains the heterochromatic state. Cell Cycle 7:3539-3547, 2008. PMCID: PMC2636745

Poleshko, A., Palagin, I., Zhang, R., Boimel, P., Castagna, C., Adams, P.D., Skalka, A.M., Katz, R.A. Identification of cellular proteins that maintain retroviral epigenetic silencing: evidence for an antiviral response. J. Virol. 82:2313-2323, 2008. PMCID: PMC2258957

Katz, R.A., Jack-Scott, E., Narezkina, A., Palagin, I., Boimel, P., Kulkosky, J., Nicolas, E., Greger, J.G., Skalka, A.M. High-frequency epigenetic repression and silencing of retroviruses can be antagonized by histone deacetylase inhibitors and transcriptional activators, but uniform reactivation in cell clones is restricted by additional mechanisms. J. Virol. 81:2592-2604, 2007. PMCID: PMC1866008

Greger, J.G., Katz, R.A., Ishov, A.M., Maul, G.G., Skalka, A.M. The cellular protein daxx interacts with avian sarcoma virus integrase and viral DNA to repress viral transcription. J. Virol. 79:4610-4618, 2005. PMCID: PMC1069566

Additional Publications

My NCBI