Γιώργος Γαρίνης
Η γήρανση αποτελεί σύνθετη βιολογική διαδικασία που αφορά στο σταδιακό εκφυλισμό ζωτικών διεργασιών του κυττάρου ενώ παράλληλα σχετίζεται με αύξηση της συχνότητας εμφάνισης παθογένειας (π.χ. νευροεκφυλισμός, διαβήτης, καρκινογένεση, αθηροσκλήρωση, οστεοπόρωση κ.τ.λ.) με τη πάροδο του χρόνου. Μέχρι σήμερα, η πολυπλοκότητα του φαινόμενου της γήρανσης, η ανεπάρκεια επαρκών μέσων για την μελέτη της αλλά και η έλλειψη κατάλληλων οργανισμών-μοντέλων κατέστησαν αδύνατη την επιβεβαίωση οποιασδήποτε υπόθεσης που να εξηγεί ικανοποιητικά τόσο τη μοριακή βάση της γήρανσης όσο και τη ρύθμιση της μακροβιότητας στους ευκαρυωτικούς οργανισμούς, συμπεριλαμβανομένου και του ανθρώπου. Το ερευνητικό αντικείμενο του εργαστηρίου αφορά στη διαλεύκανση του ρόλου των γενετικών και περιβαλλοντικών παραγόντων στη διαδικασία της γήρανσης και της μακροβιότητας στους ευκαρυωτικούς οργανισμούς.
Ο κύριες ερευνητικές κατευθύνσεις του εργαστηρίου αφορούν:
α. στη κατανόηση των επιπτώσεων της σταδιακής συσσώρευσης των γενετικών βλαβών σε ζωτικές/βασικές λειτουργίες του ευκαρυωτικού κυττάρου (μεταγραφή και διπλασιασμός του DNA, λειτουργία επιλεγμένων οργανιδίων).
β. στη κατανόηση των μηχανισμών απόκρισης που εμπλέκονται στη συσσώρευση των γενετικών βλαβών στο DNA με την πάροδο του χρόνου.
γ. στο προσδιορισμό των συντηρημένων μοριακών μονοπατιών και γενετικών παραγόντων που ρυθμίζουν τη μακροβιότητα στους ευκαρυωτικούς οργανισμούς.
Goulielmaki E, Ioannidou A, Tsekrekou M, Stratigi K, Poutakidou IK, Gkirtzimanaki K, Aivaliotis M, Evangelou K, Topalis P, Altmüller J, Gorgoulis VG, Chatzinikolaou G, Garinis GA. (2020) Tissue-infiltrating macrophages mediate an exosome-based metabolic reprogramming upon DNA damage. Nat Commun. 11:42.
Chatzinikolaou G, Apostolou Z, Aid-Pavlidis T, Ioannidou A, Karakasilioti I, Papadopoulos GL, Aivaliotis M, Tsekrekou M, Strouboulis J, Kosteas T, Garinis GA. (2017) ERCC1-XPF cooperates with CTCF and cohesin to facilitate the developmental silencing of imprinted genes. Nat Cell Biol. 19:421-432.
Karakasilioti I, Kamileri I, Chatzinikolaou G, Kosteas T, Vergadi E, Robinson AR, Tsamardinos I, Rozgaja TA, Siakouli S, Tsatsanis Ch, Niedernhofer LJ, Garinis GA. (2013) DNA damage triggers a chronic auto-inflammatory response leading to fat depletion in NER progeria. Cell Metab. 18:403-415.
Kamileri I, Karakasilioti I, Sideri A, Kosteas T, Tatarakis A, Talianidis I, Garinis GA. Defective transcription initiation causes postnatal growth failure in a mouse model of NER progeria. (2012) Proc Natl Acad Sci U S A. 109:2995-3000.
Garinis GA, Uittenboogaard LM, van IJcken W, Breit TM, van Steeg H, Mullenders LHF, van der Horst GTJ, Hoeijmakers JHJ, Schumacher B. (2009) Persistent transcription-blocking DNA lesions trigger somatic growth attenuation associated with longevity. Nat Cell Biol. 11:604-615.
Evi Goulielmaki, Anna Ioannidou, Maria Tsekrekou, Kalliopi Stratigi, Ioanna K. Poutakidou, Katerina Gkirtzimanaki, Michalis Aivaliotis, Konstantinos Evangelou, Pantelis Topalis, Janine Altmüller, Vassilis G. Gorgoulis, Georgia Chatzinikolaou and George A. Garinis' Tissue-infiltrating macrophages mediate an exosome-based metabolic reprogramming upon DNA damage. Nature Communications 2020 (in press).
Apostolou Z, Chatzinikolaou G, Stratigi K, Garinis GA. Nucleotide Excision Repair and Transcription-Associated Genome Instability. Bioessays. 2019 Apr;41(4):e1800201. doi: 10.1002/bies.201800201. Review.
Chatzinikolaou G, Apostolou Z, Aid-Pavlidis T, Ioannidou A, Karakasilioti I, Papadopoulos GL, Aivaliotis M, Tsekrekou M, Strouboulis J, Kosteas T, Garinis GA (2017). ERCC1-XPF cooperates with CTCF and cohesin to facilitate the developmental silencing of imprinted genes. Nat Cell Biol. 2017 May;19(5):421-432. doi: 10.1038/ncb3499. Epub 2017 Apr 3.
Garinis GA, Schwer B, Schumacher B (2017). Editorial: DNA Damage & Immunity. Mech Ageing Dev. pii: S0047-6374(17)30097-0. doi: 10.1016/j.mad.2017.04.006.
Stratigi K, Chatzidoukaki O, Garinis GA (2016). DNA damage-Induced Inflammation and Nuclear Architecture. Mech Ageing Dev. pii: S0047-6374(16)30175-0. doi: 10.1016/j.mad.2016.09.008.
Ioannidou A, Goulielmaki E, Garinis GA (2016). DNA Damage: From Chronic Inflammation to Age-Related Deterioration. Front Genet. 2016 Oct 25;7:187. eCollection 2016.
Oliverio M, Schmidt E, Mauer J, Baitzel C, Hansmeier N, Khani S, Konieczka S, Pradas-Juni M, Brodesser S, Van TM, Bartsch D, Brönneke HS, Heine M, Hilpert H, Tarcitano E, Garinis GA, Frommolt P, Heeren J, Mori MA, Brüning JC, Kornfeld JW. Dicer1-miR-328-Bace1 signalling controls brown adipose tissue differentiation and function. Nat Cell Biol. 2016 Mar;18(3):328-36. doi: 10.1038/ncb3316.
Visser WE, Bombardieri CR, Zevenbergen C, Barnhoorn S, Ottaviani A, van der Pluijm I, Brandt R, Kaptein E, van Heerebeek R, van Toor H, Garinis GA, Peeters RP, Medici M, van Ham W, Vermeij WP, de Waard MC, de Krijger RR, Boelen A, Kwakkel J, Kopchick JJ, List EO, Melis JP, Darras VM, Dollé ME, van der Horst GT, Hoeijmakers JH, Visser TJ. Tissue-Specific Suppression of Thyroid Hormone Signaling in Various Mouse Models of Aging. PLoS One. 2016 Mar 8;11(3):e0149941. doi: 10.1371/journal.pone.0149941.
Zacharioudaki E, Housden BE, Garinis G, Stojnic R, Delidakis C, Bray SJ. Genes implicated in stem cell identity and temporal programme are directly targeted by Notch in neuroblast tumours. Development. 2016 Jan 15;143(2):219-31. doi: 10.1242/dev.126326.
Chatzinikolaou G, Karakasilioti I, Garinis GA. DNA Damage and Innate Immunity: Links & Trade-offs. Trends Immunol. 2014 Jul 8. pii: S1471-4906(14)00107-0. doi: 10.1016/j.it.2014.06.003.
Karakasilioti I, Garinis GA. Tissue-specific aging: a tale of functional asymmetry. Aging (Albany NY). 2014 Jan 30.
Karakasilioti I, Kamileri I, Chatzinikolaou G, Kosteas T, Vergadi E, Robinson AR, Tsamardinos I, Rozgaja TA, Siakouli S, Tsatsanis Ch, Niedernhofer LJ, Garinis GA. DNA damage triggers a chronic auto-inflammatory response leading to fat depletion in NER progeria. Cell Metab. 2013 Sep 3;18(3):403-15. doi: 10.1016/j.cmet.2013.08.011.
Charlton JJ, Chatzidakis I, Tsoukatou D, Boumpas DT, Garinis GA, Mamalaki C. Programmed Death-1 Shapes Memory Phenotype CD8 T Cell Subsets in a Cell-Intrinsic Manner. J Immunol. 2013 May 17.
Kamileri I, Karakasilioti I, Garinis G. Nucleotide Excision Repair: New Tricks with Old Bricks. Trends Genet. 2012 Nov;28(11):566-73. doi: 10.1016/j.tig.2012.06.004.
Tilstra J, Robinson A, Wang J, Gregg S, Clauson C, Reay D, Nasto L, Croix C, Usas A, Vo N, Huard J, Clemens P, Stolz D, Guttridge D, Watkins SC, Garinis GA, Wang Y, Niedernhoffer L, Robbins P. NF-κB inhibition delays DNA damage-induced senescence and aging in mice. J Clin Invest. 2012 Jun 18. pii: 45785. doi: 10.1172/JCI45785.
Kamileri I, Karakasilioti I, Sideri A, Kosteas T, Tatarakis A, Talianidis I and Garinis GA. Defective transcription initiation causes postnatal growth failure in a mouse model of NER progeria. Proceedings of the National Academy of Sciences, USA 2012 Feb 21;109(8):2995-3000.
Gregg SQ, Gutierrez V, Robinson AR, Woodell T, Nakao A, Ross MA, Michalopoulos GK, Rigatti L, Rothermel CE, Kamileri I, Garinis G, Stolz DB, Niedernhofer LJ. A mouse model of accelerated liver aging due to a defect in DNA repair. Hepatology 2012 Feb;55(2):609-21.
Garinis GA, Schumacher B. Transcription-blocking DNA damage in aging and longevity. Cell Cycle 2009 Jul 15;8(14):2134-5.
Garinis GA, Uittenboogaard LM, van IJcken W, Breit TM, van Steeg H, Mullenders LHF, van der Horst GTJ, Hoeijmakers JHJ and Schumacher B. Persistent DNA damage suppresses the IGF-1R and GHR growth axis directly and cell-autonomously. Nat Cell Biol. 2009 May;11(5):604-15.
Schumacher B, Hoeijmakers JH, Garinis GA. Sealing the gap between nuclear DNA damage and longevity. Mol Cell Endocrinol. 2009 Feb 5;299(1):112-7.
Garinis GA, Gijsbertus van der Horst, Hoeijmakers JH. DNA damage and aging: new-age ideas for an age-old problem. Nature Cell Biology 2008 Nov;10(11):1241-7.
Schumacher B, van der Pluijm I, Moorhouse MJ, Theodore Kosteas, Rasile Robinson A, Suh Y, Breit TM, van Steeg H, Niedernhofer LJ, van Ijcken W, Bartke A, Spindler SR, Hoeijmakers JHJ, van der Horst GTJ and Garinis GA. Delayed and accelerated aging share common longevity assurance mechanisms. PLoS Genetics 2008 Aug 15;4(8):e1000161.
Garinis GA. Nucleotide excision repair deficiencies and the somatotropic axis in aging. Hormones (Athens). 2008 Jan-Mar;7(1):9-16.
Schumacher B, Garinis GA. and Hoeijmakers JA. Age to Survive: DNA damage and aging. Trends Genet. 2008 Feb; 24 (2): 77-85.
Garinis GA, Patil CK, Schgumacher B. The molecular basis of aging": the Boehringer Ingelheim Fonds 95th International Titisee Conference. Mech Ageing Dev. 2007 Jul-Aug;128(7-8):469-75.
Gorgels T, van der Pluijm I, Brandt RMC, Garinis GA , van Steeg H, van den Aardweg G, Jansen GH, Ruijter JM, Bergen A, van Norren D, Hoeijmakers JH, van der Horst GTJ. Retinal degeneration and ionizing radiation hypersensitivity in a mouse model for Cockayne syndrome. Mol Cell Biol. 2007 Feb;27(4):1433-41.
Hanada K, Vermeij M, Garinis GA, de Waard MC, Kunen MGS, Maas A, Duncker DJ, Meijers C, Kanaar R, Essers J. Reduction of Fibulin-4 expression affects elastic fibre development and results in aortic valve abnormalities and aneurysm. Circ Res. 2007 Mar 16;100(5):738-46.
Niedernhofer LJ, Garinis GA, Raams A, Appeldoorn E, Lalai AS, Odijk H, Oostendorp R, Ahmad A, Robinson AR, Nair P, Calder R. Brent, van Leeuwen W, Theil AF, Vermeulen W, van der Horst GTJ, Meinecke P, Kleijer WJ, Vijg J, Jaspers NGJ, Hoeijmakers JHJ. A New Progeria Links the DNA Damage Response with Life Span Regulators. Nature. 2006 Dec 21;444(7122):1038-43.
van der Pluijm I, Garinis GA, Brandt RMC, Gorgels TGMF, Wijnhoven SW, Diderich KEM, Mitchell JR, van Oostrom C, Beems R, Niedernhofer LJ, Velasco S, Friedberg EC, Tanaka K, van Steeg H, Hoeijmakers JHJ and van der Horst GTJ. Impaired Genome Maintenance Suppresses the GH/IGF1 Axis in Cockayne Syndrome Mice. PLoS Biol. 2006 Dec 12;5(1):e2.
Kurek D, Garinis GA, van Doorninck JH, van der Wees J, Grosveld FG. Transcriptome analysis reveals aberrant Gata3-dependent sig nalling pathways in murine epidermis and hair follicles. Development. 2007 Jan;134(2):261-72.
van de Ven M, Andressoo JO, Holcomb VB, Hasty P, Suh Y, van Steeg H, Garinis GA, Hoeijmakers JH, Mitchell JR. Extended longevity mechanisms in short-lived progeroid mice: identification of a preservative stress response associated with successful aging. Mech Ageing Dev. 2007 Jan;128(1):58-63.
Jans J, Garinis GA, Schul W, van Oudenaren A, Moorhouse M, Smid M, Sert Y, van der Velde A, Rijksen Y, de Gruijl FR, van der Spek PJ, Yasui A, Hoeijmakers JHJ, Leenen P, van der Horst GTJ. Differential role of basal keratinocytes in UV-induced immunosuppression and skin cancer. Mol Cell Biol. 2006 Nov;26(22):8515-26.
Garinis GA, Judith J and van der Horst GTJ. Photolyases: capturing the light to battle skin cancer. Future Oncol. 2006 Apr; 2(2): 191-9. Review.
Garinis GA, Mitchell JR, Moorhouse MJ, Hanada K, de Waard H, Vandeputte D, Jans J, Brand K, Smid M, van der Spek PJ, Hoeijmakers JH, Kanaar R, van der Horst GT. Transcriptome analysis reveals cyclobutane pyrimidine dimers as a major source of UV-induced DNA breaks. EMBO J. 2005; 16; 24(22): 3952-62.
Sklavounou-Andrikopoulou A, Chrysomali E, Iakovou M, Garinis GA, Karameris A. Elevated serum levels of the apoptosis related molecules TNF-alpha, Fas/Apo-1 and Bcl-2 in oral lichen planus. J Oral Pathol Med. 2004; 33(7): 386-90.
Menounos PG, Garinis GA, Patrinos GP. Glucose-6-phosphate dehydrogenase deficiency does not result from mutations in the promoter region of the G6PD gene. J Clin Lab Anal. 2003; 17(3): 90-2.
Garinis GA, Manolis EN, Spanakis NE, Patrinos GP, Peros G, Menounos PG. Related Articles, Links Abstract High frequency of concomitant nm23-H1 and E-cadherin transcriptional inactivation in primary non-inheriting colorectal carcinomas. J Mol Med. 2003; 81(4): 256-63.
Garinis GA, Spanakis NE, Menounos PG, Manolis EN, Peros G. Transcriptional impairment of beta-catenin/E-cadherin complex is not associated with beta-catenin mutations in colorectal carcinomas. Br J Cancer. 2003; 88(2): 206-9. *Corresponding author.
Garinis GA, Menounos PG, Spanakis NE, Papadopoulos K, Karavitis G, Parassi I, Christeli E, Patrinos GP, Manolis EN, Peros G. Hypermethylation-associated transcriptional silencing of E-cadherin in primary sporadic colorectal carcinomas. J Pathol. 2002; 198(4): 442-9.
Garinis GA, Patrinos GP, Spanakis NE, Menounos PG. DNA hypermethylation: when tumour suppressor genes go silent. Hum Genet. 2002; 111(2): 115-27.
Spanakis NE, Garinis GA, Alexopoulos EC, Patrinos GP, Menounos PG, Sklavounou A, Manolis EN, Gorgoulis VG, Valis D. Cytokine serum levels in patients with chronic HCV infection. J Clin Lab Anal. 2002; 16(1): 40-6.
Garinis GA, Gorgoulis VG, Mariatos G, Zacharatos P, Kotsinas A, Liloglou T, Foukas P, Kanavaros P, Kastrinakis NG, Vassilakopoulos T, Vogiatzi T, Field JK, Kittas C. Association of allelic loss at the FHIT locus and p53 alterations with tumour kinetics and chromosomal instability in non-small cell lung carcinomas (NSCLCs). J Pathol. 2001; 193(1): 55-65.
Gorgoulis VG, Zacharatos P, Kotsinas A, Mariatos G, Liloglou T, Vogiatzi T, Foukas P, Rassidakis G, Garinis G, Ioannides T, Zoumpourlis V, Bramis J, Michail PO, Asimacopoulos PJ, Field JK Kittas C. Altered expression of the cell cycle regulatory molecules pRb, p53 and MDM2 exert a synergetic effect on tumor growth and chromosomal instability in non-small cell lung carcinomas (NSCLCs). Mol Med. 2000; 6(3): 208-37.
Menounos P, Zervas C, Garinis G, Doukas C, Kolokithopoulos D, Tegos C, Patrinos GP. Molecular heterogeneity of the glucose-6-phosphate dehydrogenase deficiency in the Hellenic population. Hum Hered. 2000; 50(4): 237-41.
Garinis G, Patrinos GP, Menounos P, Spanakis N, Gorgoulis VG, Theodorou V, Ioannidis T, Karameris A, Valis D. Evaluation of a minipool reverse transcription-PCR screening method for the detection of hepatitis C virus infection in hemodialysis patients. Clin Chem. 2000;46(4):583-4.
Patrinos GP, Garinis G, Kounelis S, Kouri E, Menounos P. A novel 23-bp deletion in exon 5 of the p53 tumor suppressor gene. J Mol Med. 1999; 77(9):686-9.
Spanakis NE, Gorgoulis V, Mariatos G, Zacharatos P, Kotsinas A, Garinis G, Trigidou R, Karameris A, Tsimara-Papastamatiou H, Kouloukousa M, Manolis EN, Kittas C. Aberrant p16 expression is correlated with hemizygous deletions at the 9p21-22-chromosome region in non-small cell lung carcinomas. Anticancer Res. 1999; 19(3A): 1893-9.
Garinis G, Spanakis N, Theodorou V, Gorgoulis V, Manolis E, Karameris A, Valis D. Comparison of the enzyme-linked immunosorbant assay III, recombinant immunoblot third generation assay, and polymerase chain reaction method in the detection of hepatitis C virus infection in haemodialysis patients. J Clin Lab Anal. 1999; 13(3):122-5.