Dr Zuzana Horejsi

Dr Zuzana Horejsi

MSc, PhD
Centre: Centre for Molecular Oncology
Lecturer
This email address is being protected from spambots. You need JavaScript enabled to view it.

My lab focuses on:

  • discovering functions of phosphorylation induced by damaged DNA in normal and cancer cells
  • investigating the role of different phosphorylation events in cancer development.

Research Details

DNA is continually exposed to damaging agents such as UV light or products of cellular metabolism. Exposure to these agents can result in damage leading to harmful DNA mutations. Such mutations can dis-regulate cellular division and development and subsequently trigger transformation of normal cells into cancer cells. Cells therefore have DNA damage repair mechanisms, which are essential for their survival and act as an anti-cancer barrier.

The DNA repair mechanisms are controlled and regulated by phosphorylation signalling, which can activate or deactivate phosphorylated proteins or create unique binding sites for other proteins. Mutations of kinases that carry out phosphorylation involved in DNA damage response are frequently found in tumours; drugs that inhibit their enzymatic activity are already used as cancer chemotherapeutics.

My lab aims to identify novel protein interactions dependent on phosphorylation between DNA damage response proteins. We also aim to identify kinases, responsible for the phosphorylation and discover their precise function in the DNA damage response.

We hope that our work will bring deeper understanding of the DNA damage response, its regulation and interplay with other cellular processes. Understanding how DNA damage repair is carried out and regulated is essential for identification and further development of new and more efficient cancer treatments.


PhD student Mr Patrick von Morgen: currently at the Institute of Molecular Genetics, Prague, Czech Republic.

Profile

  • 2016 I received Sir Henry Dale Fellowship and joined Barts Cancer Institute as a lecturer at the Centre of Molecular Oncology.
  • 2014 Senior Scientific Officer in the DNA Damage Response Laboratory, Clare Hall Laboratories, The Francis Crick Institute, London, UK. I continued on discovering new phosphorylation events important for regulation of the DNA Damage Response.
  • 2007 Postdoctoral Fellow in the DNA Damage Response Laboratory, Clare Hall Laboratories, London Research Institute, Cancer Research UK, London, UK, led by Dr Boulton. I have been studying the role of Casein Kinase 2 in DNA damage response and discovered a new phospho-bidning domain PIH-N.
  • PhD viva in 2006 at Charles University in Prague. The main part of my PhD work was done under supervision of Prof Bartek at the Department of Cell Cycle and Cancer, Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark. I was investigating the role of the DNA damage checkpoint in normal and cancer cell cycle.
  • MSc degree in 2001 at Charles University in Prague, Czech Republic. The thesis was carried out at Department of Molecular Virology, Institute of Molecular Genetics, Czech Academy of Sciences, Prague, Czech Republic, under supervision of Dr Dvorak. I was studying the role of transcription factor c-Myb in the development and differentiation of the red blood cells.

Funding

  • 2016 - 2021: Wellcome Trust, Sir Henry Dale Fellowship. "Identification of novel protein interactions within DNA damage pathways regulated by non-canonical and novel DNA damage kinases." £954,102

Key Publications

CK2-dependent PIH1D1 interactions define substrate specificity of the R2TP co-chaperone complex. Hořejší Z*, Stach L*, Flower TG, Joshi D, Flynn H, Skehel JM, O’Reilly NJ, Ogrodowicz RW, Smerdon SJ, Boulton SJ. Cell Rep 7: 19-26, 2014, PMID: 24656813. (*shared first authors)

CK2 phospho-dependent binding of R2TP complex to TEL2 is essential for mTOR and SMG1 stability. Hořejší Z, Takai H, Adelman CA, Collis SJ, Flynn H, Maslen S, Skehel JM, de Lange T, Boulton SJ. Mol. Cell 39: 839-50, 2010, PMID: 20864032.

Poly(ADP-ribose)-dependent regulation of DNA repair by the chromatin remodeling enzyme ALC1. Ahel D, Hořejší Z, Wiechens N, Polo SE, Garcia-Wilson E, Ahel I, Flynn H, Skehel M, West SC, Jackson SP, Owen-Hughes T, Boulton SJ. Science 325: 1240-3, 2009, PMID: 19661379.

DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Bartkova J, Hořejší Z, Koed K, Kramer A, Tort F, Zieger K, Guldberg P, Sehested M, Nesland JM, Lukas C, Orntoft T, Lukas J, Bartek J. Nature 434: 864-70, 2005, PMID: 15829956.

My lab focuses on:

  • discovering functions of phosphorylation induced by damaged DNA in normal and cancer cells
  • investigating the role of different phosphorylation events in cancer development.

News

The lab was formed this August and currently has one postdoc position available.

Please contact me if you are interested.

See other researchers working on:

Cell Signalling Genetics
This site uses cookies in order to function properly. By continuing to browse, you agree that we can save them on your device. Privacy Policy.