PROJECT
SUPERVISORS
Project Supervisor
Antonis Kirmizis
Background
I am a tenured professor of Epigenetics at the Department of Biological Sciences at the University of Cyprus (UCY). My scientific career began with pursuing undergraduate studies in Biology at Lawrence University, USA. While working on my undergraduate thesis project, I developed an interest to understand the molecular mechanisms that control gene transcription. To explore this, I joined the lab of Prof. Farnham at the McArdle Cancer Institute of the University of Wisconsin-Madison, USA, where, as part of my PhD project, I investigated the function of newly identified cancer-associated chromatin factors in transcription
At the time when I graduated, the impact of chromatin structure in genome regulation was gaining ground. Having decided to follow the academic route, I joined the lab of Prof Kouzarides at Cambridge University UK, as a Marie-Curie postdoctoral fellow, to investigate how chromatin modifications and their associated enzymes regulate gene expression. With my extensive background in chromatin, transcription and cancer biology, I established a research group at UCY in 2010 with the aim to further our knowledge on epigenetic regulation and its impact in cancer.
Research
The overall aim of our group is to understand how epigenetic mechanisms, such as those involving histone modifications, control genome functions. We are driven by the fact that dysregulation of these epigenetic mechanisms is linked to cancer and therefore, unravelling these mechanisms will potentially lead towards new therapies. To accomplish this, we employ interdisciplinary methods including molecular, biochemical, and genetic techniques coupled to omics approaches. Initially our group was one of the first to define the cellular role of histone N-terminal acetylation and of its associated enzyme Naa40 in transcription and carcinogenesis.
In recent years, we found that Naa40 controls the transcription of key metabolic genes, thus fuelling our interest in how epigenetic mechanisms and cellular metabolism cross-regulate each other. Following this interest, we recently demonstrated that histone acetylation can serve as an acetate reservoir, contributing carbon atoms directly to other metabolic processes like lipid synthesis. As part of NUCLEAR we aim to explore further this moonlighting role of histone modifications and determine the importance of this function in carcinogenesis.
Publications
Hyperacetylated histone H4 is a source of carbon contributing to lipid synthesis.
Charidemou E, Noberini R, Ghirardi C, Georgiou P, Marcou P, Theophanous A, Strati K, Keun H, Behrends V, Bonaldi T, Kirmizis A. EMBO Journal, 43(7):1187-1213, 2024. doi: 10.1038/s44318-024-00053-0
Cellular effects of NAT-mediated histone N-terminal acetylation.
Constantinou M, Klavaris A, Koufaris C, Kirmizis A. J Cell Science, 136(7):jcs260801, 2023. doi: 10.1242/jcs.260801
Histone acetyltransferase NAA40 modulates acetyl-coA levels and lipid synthesis.
Charidemou E, Tsiarli M, Theofanous A, Yilmaz V, Pitsouli C, Strati K, Griffin JL, Kirmizis A. BMC Biology, 20(1):22, 2022. doi: 10.1186/s12915-021-01225-8
Histone acetyltransferase NAA40 links one-carbon metabolism to chemoresistance.
Demetriadou C, Raoukka A, Charidemou E, Mylonas C, Michael C, Parekh S, Koufaris C, Skourides P, Papageorgis P, Tessarz P, Kirmizis A. Oncogene, 41(4):571-585, 2022. doi: 10.1038/s41388-021-02113-9
NAA40 contributes to colorectal cancer growth by controlling PRMT5 expression.
Demetriadou C, Pavlou D, Mpekris F, Achilleos C, Stylianopoulos T, Zaravinos A, Papageorgis P, Kirmizis A. Cell Death & Disease, 10(3):236, 2019. doi: 10.1038/s41419-019-1487-3