Prof. Achilleas Gravanis

B8: Foundation for Research and Technology Hellas​,  Greece
Institute of Molecular Biology and Biotechnology

Position
Professor of Pharmacology, Medical School University of Crete, Collaborating Researcher, Institute of Molecular Biology & Biotechnology, Foundation of Research & Technology-Hellas, Affiliated Research Professor, Center of Drug Discovery Northeastern University.

Background
Developing agonists of Neurotrophin Receptors, with neuroprotective and neurogenic properties.
Neurotrophins (NT), like Nerve Growth Factor (NGF), are important factors for the development and maintenance of nervous tissue. Their decline has been associated to various neurodegenerative disorders and to brain aging. Despite the demonstrated beneficial effects, the therapeutic usefulness of neurotrophins is compromised by their polypeptide nature and their restricted penetrance to the blood-brain barrier. We are developing synthetic small molecules, with neuroprotective and neurogenic properties, shown to interact and signal through neurotrophin receptors (microneurotrophins), The efficacy of synthetic microneurotrophins as neuroprotective and neurogenic agents in vivo is tested in animal models of neurodegenerative disorders and brain trauma.

3D Scaffolds hosting neural stem cells: developing Neuroimplants and Neurobiosensors. 
Neural stem cells (NSC) emerge as new therapeutic agents with potential applications in neuronal injury and repair. In responding tothis challenge we develop3D micro/nano scaffolds for hosting NSC 3D cultures, as an advantageous platform to study the biology and neurochemistry of NSC proliferation, differentiation, neuritogenesis and synaptogenesis in vitro. The functionality of the neuronal networks developed onto 3D scaffolds is tested using a combination of state-of-the-art technologies, including two-photo imaging, advanced electrophysiology, functional genomics and proteomics.  The 3D NSC scaffolds are tested in two applications: i) 3D neuroimplants, for effectively bridging interrupted spinal cord, using animal models, ii) 3D neurobiosensors for screening for new neurogenic compounds.

Role in EuroNeurotrophin
Main Supervisor ESR 11 and ESR 12, WP2 Leader
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Key Publications

• Bonetto G, Charalampopoulos I, Gravanis A, Karagogeos D. (2017) The novel synthetic microneurotrophin BNN27 protects mature oligodendrocytes against cuprizone-induced death, through the NGF receptor TrkA. Glia, 65:1376-1394
• Pitsikas N, Gravanis A. (2017) The novel DHEA derivative, BNN27 counteracted delay-dependent and scopolamine-induced recognition memory deficits in rats. Neurobiology of Learning & Memory, 6;140:145-153
• Gravanis A, Pediaditakis I, Charalampopoulos I. (2017) Synthetic microneurotrophins in therapeutics of neurodegeneration. Oncotarget. 2017 /oncotarget.14667 (Invited Editorial)
• Pediaditakis I, Kourgiantaki A, Prousis KC, Potamitis C, Xanthopoulos KP, Zervou M, Calogeropoulou T, Charalampopoulos I, Gravanis A. (2016). BNN27, a 17-Spiroepoxy Steroid Derivative, Interacts With and Activates p75 Neurotrophin Receptor, Rescuing Cerebellar Granule Neurons from Apoptosis. Front Pharmacol. 7:512-530.
• Pediaditakis I, Efstathopoulos P, Prousis KC, Zervou M, Arévalo JC, Alexaki VI, Nikoletopoulou V, Karagianni E, Potamitis C, Tavernarakis N, Chavakis T, Margioris AN, Venihaki M, Calogeropoulou T, Charalampopoulos I, Gravanis A. (2016) Selective and differential interactions of BNN27, a novel C17-spiroepoxy steroid  derivative, with TrkA receptors, regulating neuronal survival and differentiation. Neuropharmacology. 11:266-282
• Simitzi C, Efstathopoulos P, Kourgiantaki A, Ranella A, Charalampopoulos I, Fotakis C, Athanassakis I, Stratakis E, Gravanis A. (2015) Laser fabricated discontinuous anisotropic microconical substrates as a new model scaffold to control the directionality of neuronal network outgrowth. Biomaterials. 67:115-128
• Pediaditakis I, Iliopoulos I, Theologidis I, Delivanoglou N, Margioris AN, Charalampopoulos I, Gravanis A. (2015) Dehydroepiandrosterone: an ancestral ligand of neurotrophin receptors. Endocrinology. 156:16-23
• Lazaridis I, Charalampopoulos I, Alexaki VI, Avlonitis N, Pediaditakis I, Efstathopoulos P, Calogeropoulou T, Castanas E, Gravanis A. (2011) Neurosteroids interacts with nerve growth factor (NGF) receptors, preventing neuronal apoptosis. PLoS Biol 9(4):e1001051.
• Calogeropoulou T, Avlonitis N,  Minas V, Pantzou A, Alexi X, Charalampopoulos I, Zervou M, Vergou V, Lazaridis I, Alexis MN, Gravanis A. (2009). Novel dehydroepiandrosterone derivatives with anti-apoptotic, neuroprotective activity.  J Med Chem, 52:6569-6587
• Charalampopoulos I, Remboutsika M, Margioris A, Gravanis A. (2008) Neurosteroids as endogenous modulators of neurogenesis and neuronal survival. Trends Endocrinol Metab 19:300-307
• Charalampopoulos I, Tsatsanis C, Dermitzaki E, Alexaki VI, Castanas E, Margioris AN, Gravanis A. (2004) Dehydroepiandrosterone and allopregnanolone protect sympathoadrenal medulla cells against apoptosis via antiapoptotic Bcl-2 proteins. PNAS. 101:8209-8214