Androniki Kretsovali

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Androniki Kretsovali

Emerita Research Director

Our lab investigates the mechanisms by which transcriptional, epigenetic and signal transduction factors regulate cell fate. We have recently focused our interest on Promyelocytic Leukemia Protein (PML) a multitasking protein and organizer of the PML-NBs in embryonic and neuronal stem cells. Specifically, we study:

1. The role of PML in mouse embryonic stem cells (ESC) pluripotency
Our previous work demonstrated that PML regulates ES cell–cycle progression and promotes both naïve and induced pluripotency. To elucidate the molecular pathways underlying these effects, we characterized the PML-dependent proteomic and SUMO-proteomic landscapes in ES cells.

2. The role of PML in the nervous system
In the nervous system, PML has been implicated in brain development, circadian rhythm regulation, synaptic plasticity, and the degradation of misfolded proteins. Despite these associations, its role in neuro-inflammation and neurodegeneration remains largely unexplored.

To investigate the contribution of PML to neural stem cell (NSC) physiology and stress responses, we analyzed E13.5 NSCs derived from wild-type and Pml⁻/⁻ mice. Functional assays were integrated with transcriptomic and proteomic analyses.

Given that PML-deficient NSCs display features reminiscent of neurodegeneration, we further explored a potential link between PML and Alzheimer’s disease (AD) pathology using both the 5XFAD transgenic mouse model and an acute neuroinflammation model induced by intracerebroventricular (ICV) injection of β-amyloid (Aβ).

Selected Publications
More Publications

Spanou S, Makatounakis T, Deligianni E, Papanikolaou S, Samiotaki M, Moretto F, Nikolaou C, Papamatheakis J, Kretsovali A. (2025) PML is crucial for neural stem cell differentiation, stress tolerance and mitochondrial integrity. Stem Cell Reports. 20:102598.

Spanou S, Makatounakis T, Filippopoulou C, Dougalis G, Stamatakis G, Nikolaou C, Samiotaki M, Chachami G, Papamatheakis J, Kretsovali A. (2025) Promyelocytic Leukemia Protein (PML) Regulates Stem Cell Pluripotency Through Novel Sumoylation Targets. Int J Mol Sci. 26:1145.

Vogiatzoglou AP, Spanou S, Sachini N, Drakos E, Nikolaou C, Makatounakis T, Kretsovali A, Papamatheakis J. (2023) Promyelocytic leukemia protein regulates angiogenesis and epithelial-mesenchymal transition to limit metastasis in MDA-MB-231 breast cancer cells. Mol Oncol. 17:2090-2108.

Vogiatzoglou AP, Moretto F, Makkou M, Papamatheakis J, Kretsovali A.(2022) Promyelocytic leukemia protein (PML) and stem cells: from cancer to pluripotency. Int J Dev Biol. 66:85-95.

Chanoumidou K, Hadjimichael C, Athanasouli P, Ahlenius H, Klonizakis A, Nikolaou C, Drakos E, Kostouros A, Stratidaki I, Grigoriou M, Kretsovali A. (2018)
Groucho related gene 5 (GRG5) is involved in embryonic and neural stem cell state decisions. Sci Rep. 8:13790.

Spanou S, Makatounakis T, Deligianni E, Papanikolaou S, Samiotaki M, Moretto F, Nikolaou C, Papamatheakis J, Kretsovali A.
PML is crucial for neural stem cell differentiation, stress tolerance and mitochondrial integrity. Stem Cell Reports. 2025 Sep 9;20(9):102598. doi: 10.1016/j.stemcr.2025.102598.

Vogiatzoglou AP, Spanou S, Sachini N, Drakos E, Nikolaou C, Makatounakis T, Kretsovali A, Papamatheakis J.
Promyelocytic leukemia protein regulates angiogenesis and epithelial-mesenchymal transition to limit metastasis in MDA-MB-231 breast cancer cells. Mol Oncol. 2023 Oct;17(10):2090-2108. doi: 10.1002/1878-0261.13501.

Kokotidou C, Tsitouroudi F, Nistikakis G, Vasila M, Papanikolopoulou K, Kretsovali A, Mitraki A.
Adenovirus Fibers as Ultra-Stable Vehicles for Intracellular Nanoparticle and Protein Delivery. Biomolecules. 2022 Feb 15;12(2):308. doi: 10.3390/biom12020308.

Vogiatzoglou AP, Moretto F, Makkou M, Papamatheakis J, Kretsovali A.
Promyelocytic leukemia protein (PML) and stem cells: from cancer to pluripotency. Int J Dev Biol. 2022;66(1-2-3):85-95. doi: 10.1387/ijdb.210154av.

Kokotidou C, Jonnalagadda SVR, Orr AA, Vrentzos G, Kretsovali A, Tamamis P, Mitraki AA.
Designer Amyloid Cell-Penetrating Peptides for Potential Use as Gene Transfer Vehicles. Biomolecules. 2019 Dec 18;10(1):7. doi: 10.3390/biom10010007. PMID: 31861408

Sachini N, Arampatzi P, Klonizakis A, Nikolaou C, Makatounakis T, Lam EW, Kretsovali A, Papamatheakis J.
Promyelocytic leukemia protein (PML) controls breast cancer cell proliferation by modulating Forkhead transcription factors. Mol Oncol. 2019 Jun;13(6):1369-1387. doi: 10.1002/1878-0261.12486. Epub 2019 May 16. PMID: 30927552

Chanoumidou K, Hadjimichael C, Athanasouli P, Ahlenius H, Klonizakis A, Nikolaou C, Drakos E, Kostouros A, Stratidaki I, Grigoriou M, Kretsovali A.
Groucho related gene 5 (GRG5) is involved in embryonic and neural stem cell state decisions. Sci Rep. 2018 Sep 13;8(1):13790.

Hadjimichael C, Chanoumidou K, Nikolaou C, Klonizakis A, Theodosi GI, Makatounakis T, Papamatheakis J, Kretsovali A.
Promyelocytic Leukemia Protein Is an Essential Regulator of Stem Cell Pluripotency and Somatic Cell Reprogramming. Stem Cell Reports. 2017 May 9;8(5):1366-1378

Hadjimichael C, Nikolaou C, Papamatheakis J, Kretsovali A.
MicroRNAs for Fine-Tuning of Mouse Embryonic Stem Cell Fate Decision through Regulation of TGF-β Signaling. Stem Cell Reports. 2016 Mar 8;6(3):292-301. doi: 10.1016/j.stemcr.2016.01.004. Epub 2016 Feb 11.

Hadjimichael C, Chanoumidou K, Papadopoulou N, Arampatzi P, Papamatheakis J, Kretsovali A.
Common stemness regulators of embryonic and cancer stem cells.World J Stem Cells. 2015 Oct 26;7(9):1150-84

Kretsovali A, Hadjimichael C, Charmpilas N.
Histone deacetylase inhibitors in cell pluripotency, differentiation, and reprogramming. Stem Cells Int. 2012, 2012:184154

Karantzali E, Lekakis V, Ioannou M, Hadjimichael C, Papamatheakis J, Kretsovali A.
Sall1 regulates embryonic stem cell differentiation in association with Nanog. J.Biol. Chem. 2011 Jan 14;286(2):1037-45

Schulz H, Kolde R, Adler P, Aksoy I, Anastassiadis K, Bader M, Billon N, Boeuf H, Bourillot PY, Buchholz F, Dani C, Doss MX, Forrester L, Gitton M, Henrique D, Hescheler J, Himmelbauer H, Hübner N, Karantzali E, Kretsovali A, Lubitz S, Pradier L, Rai M, Reimand J, Rolletschek A, Sachinidis A, Savatier P, Stewart F, Storm MP, Trouillas M, Vilo J, Welham MJ, Winkler J, Wobus AM, Hatzopoulos AK; Functional Genomics in Embryonic Stem Cells Consortium.
The FunGenES database: a genomics resource for mouse embryonic stem cell differentiation.
PLoS One. 2009 Sep 3;4(9):e6804.

Karantzal E, Schulz H, Hummel O, Hubner N, Hatzopoulos A, Kretsovali A.
Histone deacetylase inhibition accelerates the early events of stem cell differentiation: transcriptomic and epigenetic analysis. Genome Biol. 2008 Apr 4; 9 ( 4 ): R65 . [Epub ahead of print] PMID: 18394158 [PubMed - as supplied by publisher]

Gialitakis M, Kretsovali A, Spilianakis C, Kravariti L, Mages J, Hoffmann R, Hatzopoulos AK, Papamatheakis J.
Coordinated changes of histone modifications and HDAC mobilization regulate the induction of MHC class II genes by Trichostatin A. Nucleic Acids Res. 2006 Feb 1; 34 ( 3 ): 765-72. Print 2006. PMID: 16452299 [PubMed - indexed for MEDLINE]

Biel M, Kretsovali A, Karatzali E, Papamatheakis J, Giannis A.
Design, synthesis, and biological evaluation of a small-molecule inhibitor of the histone acetyltransferase Gcn5.
Angew Chem Int Ed Engl. 2004 Jul 26;43(30):3974-6. No abstract available.
PMID: 15274229 [PubMed - indexed for MEDLINE]

Muhlethaler-Mottet A, Krawczyk M, Masternak K, Spilianakis C, Kretsovali A, Papamatheakis J, Reith W.
The S box of major histocompatibility complex class II promoters is a key determinant for recruitment of the transcriptional co-activator CIITA.
J Biol Chem. 2004 Sep 24;279(39):40529-35. Epub 2004 Jul 22.
PMID: 15271997 [PubMed - indexed for MEDLINE]

Spilianakis C, Kretsovali A, Agalioti T, Makatounakis T, Thanos D, Papamatheakis J.
CIITA regulates transcription onset viaSer5-phosphorylation of RNA Pol II.
EMBO J. 2003 Oct 1;22(19):5125-36.
PMID: 14517250 [PubMed - indexed for MEDLINE]

Tzortzakaki E, Spilianakis C, Zika E, Kretsovali A, Papamatheakis J.
Steroid receptor coactivator 1 links the steroid and interferon gamma response pathways.
Mol Endocrinol. 2003 Dec;17(12):2509-18. Epub 2003 Aug 21.
PMID: 12933903 [PubMed - indexed for MEDLINE]

Mamalaki A, Gritzapis AD, Kretsovali A, Belimezi M, Papamatheakis J, Perez SA, Papamichail M, Baxevanis CN.
In vitro and in vivo antitumor activity of a mouse CTL hybridoma expressing chimeric receptors bearing the single chain Fv from HER-2/neu- specific antibody and the gamma-chain from Fc(epsilon) RI.
Cancer Immunol Immunother. 2003 Aug;52(8):513-22. Epub 2003 Apr 25.
PMID: 12715240 [PubMed - indexed for MEDLINE]

Gritzapis AD, Mamalaki A, Kretsovali A, Papamatheakis J, Belimezi M, Perez SA, Baxevanis CN, Papamichail M.
Redirecting mouse T hybridoma against human breast and ovarian carcinomas: in vivo activity against HER-2/neu expressing cancer cells.
Br J Cancer. 2003 Apr 22;88(8):1292-300.
PMID: 12698199 [PubMed - indexed for MEDLINE]

Karetsou Z, Kretsovali A, Murphy C, Tsolas O, Papamarcaki T.
Prothymosin alpha interacts with the CREB-binding protein and potentiates transcription.
EMBO Rep. 2002 Apr;3(4):361-6. Epub 2002 Mar 15.
PMID: 11897665 [PubMed - indexed for MEDLINE]

Kretsovali A, Spilianakis C, Dimakopoulos A, Makatounakis T, Papamatheakis J.
Self-association of class II transactivator correlates with its intracellular localization and transactivation.
J Biol Chem. 2001 Aug 24;276(34):32191-7. Epub 2001 Jun 18.
PMID: 11413136 [PubMed - indexed for MEDLINE]

Spilianakis C, Papamatheakis J, Kretsovali A.
Acetylation by PCAF enhances CIITA nuclear accumulation and transactivation of major histocompatibility complex class II genes.
Mol Cell Biol. 2000 Nov;20(22):8489-98.
PMID: 11046145 [PubMed - indexed for MEDLINE]

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