Dr. Michael Leichter, Marie Curie Post-Doctoral Fellow
Dr. Marija Marko, Marie Curie Post-Doctoral Fellow
Christina Papadopoulou, Ph.D. student
Georgios Boukakis, Ph.D. student
Aggeliki Korillou, Ph.D. student (in collaboration with Chemical Carcinogenesis Program)
Research objectives
The research activities of the program refer to the mechanisms underlying the regulation of gene expression at the post-transcriptional level, in mammals. In particular, mRNA processing is known to require the assembly of nascent pre-mRNA into dynamic, multi-component structures with the participation of a large number of RNA-binding proteins (RBPs), as well as of the spliceosomal U-snRNP complexes. The importance of post-transcriptional events in cell physiology is underlined by the finding of a large number of human genetic defects caused by inaccurate mRNA processing. The focus of our work has been on selected members of these components, namely the heterogeneous nuclear ribonucleoproteins (hnRNPs), and/or proteins with the dual ability to bind RNA and ssDNA.
Research is conducted on two inter-connected levels:
understanding basic regulatory processes of mRNA maturation
unraveling the nature and extent of participation of specific RBP proteins in human pathophysiology.
Research Highlights
Recent and current research activities refer to:
Deciphering novel macromolecular assemblies involved in coupling transcription to RNA processing
Defining novel networks of protein-RNA interactionsinvolved in post- transcriptional regulation of gene expression
Identifying the participation of specific RNA-binding proteins (RBPs) in malignant transformation and autoimmunity
Applying systems biology analysis to define the subset of mRNA target
molecules associated with selected RNA-binding proteins
Figure 1: Heat shock treatment induces major changes in the cellular localization of the RNA-binding proteins HuR and hnRNP A1.
FFigure 2: Comparison of the relative expression levels of the hnRNP A/B proteins in paired tumour and normal lung biopsies.
Recent Competitive Research Grants
European Union Funding:
- "Macromolecular assemblies involved in regulated gene expression: structural/functional characteristics, interplay and novel functions" Marie Curie Host Development for Transfer of Knowledge (TOK-Dev. 2004-2008). Coordinated by A. Guialis, RNA Processing Lab. and shared with A. Pintzas, Signal Mediated Gene Expression Lab and MN Alexis, Molecular Endocrinology Lab.
Participation in National Funding:
"Functional detection of diagnostic and therapeutic genes for the management of tumors of the lung and colon"
GSRT- PENED 03-ED 0264 (2006-2009)- IBEB/EIE and "Fleming "
"Mechanism of action of anticancer compounds in the cellular apoptotic process and their potential as chemotherapeutic agents"
GSRT-PENED 03-ED 0322 (2006-2009)- IBEB/EIE and "Democritos"
"Investigating the potential of applying hnRNP A2/B1 as a new marker in the early detection of lung cancer"
Ministry of Health- KESY (2006-2009) -IBEB/EIE and "Sotiria" Hospital
Recent Publications (2007 - )
A fraction of the transcription factor TAF15 participates in interactions with a subset of the spliceosomal U1 snRNP complex
M. Leichter, M. Marko, V. Ganou, M. Patrinou-Georgoula, L. Tora and A. Guialis
Submitted
Deregulated expression of hnRNP A/B proteins in human non-small cell lung cancer: parallel assessment of protein and mRNA levels in paired tumour/non-tumour tissues.
G. Boukakis, M. Patrinou-Georgoula, M. Lekarakou, C. Valavanis and A. Guialis
BMC Cancer (2010) 10, 434-446
hnRNP M interacts with PSF and p54nrb and co-localizes within defined nuclear structures
M. Marko, M. Leichter, M. Patrinou-Georgoula and A. Guialis
Exper. Cell Res. (2010) 316, 390-400
Extensive association of HuR with hnRNP proteins within immunoselected hnRNP and mRNP complexes
Ch. Papadopoulou, M. Patrinou-Georgoula and A. Guialis
Biochim. Biophys. Acta (2010)1804, 692-703.
Human U1 snRNA forms a new chromatin-associated snRNP with TAF15.
L. Jobert, N. Pinzon, E. Van Herreweghe, B.E. Jady, A. Guialis, T. Kiss and L. Tora
EMBO Rep. (2009) 10, 494-500.
Cell death induced by N-methyl-N-Nitrosourea, a model SN1 methylating agent, in two lung cancer cell lines of human origin
A. Koryllou, M.Patrinou-Georgoula, C. Troungos and V. Pletsa
Apoptosis (2009) 14, 1121-1133.
Overexpression of hnRNPA2/B1 in bronchoscopic specimens: a potential early detection marker in lung cancer
S. Katsimpoula, M. Patrinou-Georgoula, N. Makrilia, K. Dimakou , A. Guialis , K. Dimakou, D. Orfanidou and KN Syrigos
Anticancer Res., 2009, 29, 1373-1382
Comparative qualitative and quantitative analysis of scleroderma (systemic sclerosis) serologic immunoassays
L. Picha, I. Pakas, A. Guialis, H.M. Moutsopoulos and P.G. Vlachoyiannopoulos
J. Autoimmun. (2008) 31, 166-174
Multiple specificities of autoantibodies against hnRNP A/B proteins in systemic rheumatic diseases and hnRNP L as an associated novel autoantigen
S. Siapka, M. Patrinou-Georgoula, P.G. Vlachoyiannopoulos and A. Guialis
Autoimmunity (2007) 40, 223-233