Richard A. Katz, PhD

Link to

This Fox Chase professor participates in the Undergraduate Summer Research Fellowship
Learn more about Research Volunteering.

Professor

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

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.   

 

  • Link to /sites/default/files/styles/slider_desktop/public/images/slide/katz_Slide_01.jpg?itok=cXjr2y9j

    Katz Lab, 2015

  • Link to /sites/default/files/styles/slider_desktop/public/images/slide/katz_Slide_02.png?itok=MA97ksNX

    PRR14 tehers heterochromatin to the nuclear lamina through Heterochromatin Protein 1 (HP1)

  • Link to /sites/default/files/styles/slider_desktop/public/images/slide/katz_Slide03.png?itok=O9F7DOhD

    PRR14 binds anaphase chromosomes through HP1

     

    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

    People

    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). 

    Misc

    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

    Selected Publications

    Dunlevy K.L., Medvedeva V., Wilson J.E., Hoque M., Pellegrin T., Maynard A., Kremp M.M., Wasserman J.S., Poleshko A., Katz R.A., The prr14 heterochromatin tether encodes modular domains that mediate and regulate nuclear lamina targeting. J Cell Sci. 133(10)2020. PMC7272351. https://www.ncbi.nlm.nih.gov/pubmed/32317397.

    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 ... Expand

    Additional Publications

    The following ratings and reviews are based on verified feedback collected from independently administered patient experience surveys. The ratings and comments submitted by patients reflect their own views and opinions. Patient identities are withheld to ensure confidentiality and privacy. Learn more about our Patient Experience Ratings.

    Ratings Breakdown

    Loading ...

    Patient comments

    Loading ...

    This Fox Chase professor participates in the Undergraduate Summer Research Fellowship
    Learn more about Research Volunteering.