Kleopas A. Kleopa

Professor

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Current Position

Senior Neurologist, Head of Neurology Clinic E, The Cyprus Institute of Neurology & Genetics

Program Coordinator MSc/PhD Neuroscience

Course Coodrinator of NEURO101: Cellular and Molecular Neurosccience, Cyprus School of Molecular Medicine

E-mail: kleopa@cing.ac.cy

Education

MD, University of Würzburg Medical School, Germany, 1993
Doctoral Thesis with magna cum laude, Medical Faculty of the University of Würzburg, 1994
Training in Neurology in Würzburg,Germany and in Philadelphia, Drexel University USA , 1994-1999
Neuromuscular fellowship and postdoctoral research fellowship, University of Pennsylvania, USA, 1999-2002

Research Interests

The main contribution of Prof. Kleopa’s research has been the elucidation of the mechanisms causing various neurological disorders using novel experimental models, with main focus on inherited neuropathy and leukodystrophy. Furthermore, he has pioneered world-wide in the last several years the cell-targeted gene therapy approach to treat demyelinating neurological diseases. A central objective of his research has been the investigation of the cellular and molecular mechanisms that lead to the manifestation of chronic or transient encephalopathy in patients with inherited mutations in the gap junction protein connexin32 (Cx32), causing X-linked Charcot-Marie-Tooth Disease (CMT1X). Through a series of publications, he has clarified the repertoire of Schwann cell and oligodendroglial gap junction protein expression, their anatomic and functional relationship and possible interactions in health and disease. He showed that Cx32 mutations cause loss of function in CNS and PNS. Based on these results he has developed gene therapy approaches to replace connexin genes specifically in myelinating glial cells. He has pioneered gene therapy methods using both lentiviral and AAV vectors for cell-targeted expression based on cell-specific promoters. Importantly, in a ground-breaking work, his team has recently demonstrated that the clinically translatable approach of lumbar intrathecal viral vector delivery can lead to widespread expression of the delivered genes throughout the peripheral nervous system.


A further line of research in Dr. Kleopa’s lab has been the study of glial connexin pathology in acquired demyelination, examining multiple sclerosis (MS) postmortem human brain samples as well as experimental encephalomyelitis (EAE) mouse models. His team has shown widespread glial connexin pathology with loss of gap junctions in oligodendrocytes in white and gray matter lesions as well as in normal appearing MS brain with associated astrogliosis and disconnection of astrocytes from oligodendrocytes. These changes correlate with inflammation and disease progression. He has also contributed to several other important research findings including the cellular and molecular mechanisms in autoimmune encephalopathies and neuromyotonia, as well as in chemotherapy-induced neurotoxicity. He has also participated in research into therapeutic, epidemiological, immunological and genetic aspects of myasthenia gravis, motor neuron disease, and other neuromuscular and neurological disorders. 


Prof. Kleopa has published more than 80 original peer-reviewed scientific papers in international journals cited in PubMed and more than 16 book chapters. His published work has received more than 4000 citations to date (H-index 29). In most of these papers he was the leading author. Many of his research papers have been published in prestigious high-impact international interdisciplinary or neuroscience journals.

 

 

Biography

Prof. Kleopa completed his medical studies at the University of Wuerzburg, Germany in 1987-1993, and obtained his doctoral degree from the same University in 1994 with magna cum laude. He completed his Neurology residency at Drexel University in Philadelphia, USA in 1999, followed by a 2-year fellowship in neuromuscular disorders and electromyography at the University of Pennsylvania. He was appointed as clinical instructor in Neurology at the Faculty of the Hospital of the University of Pennsylvania in in 2001. He was recruitment at the Cyprus Institute of Neurology and Genetics in 2002, where he was appointed Senior Consultant Neurologist. He established specialized clinics in Neurology and electromyography as well as an externally funded Neuroscience Research Lab. He became head of Neurology Clinic E and Neuroscience Lab in 2007. He is a Professor at the Cyprus School of Molecular Medicine (CSMM) since its establishment in 2012 and serves as Coordinator of the Neuroscience MSc/PhD Program since it was started in 2015. He is also teaches the Cellular and Molecular Neuroscience Course. He supervises MSc and PhD students for their research projects in the lab, and teaches also medical students and neurology residents and fellows in the clinic.


Prof. Kleopa has been the principal investigator in at least 20 successful research projects with total external funding from national and international sources exceeding 2 million Euros in the last 17 years. He has established collaborations with leading scientists in top rank academic institutions in Europe and the USA. He is a member of numerous professional societies and associations. 

 

 

Awards

Prof. Kleopa has received many prestigious National and International Awards for his academic achievements including: scholarships to attend Medical School by the Cyprus Government as well as by the German Academic exchange Service (DAAD) (1987-1993), Distinction in Neuroscience and Participation in an Erasmus Winter School (1990), Neurology Teaching Award (1999), a Bursary Award of the EFNS (2003) and a Fellowship Award of the Peripheral Nerve Society (2009). 
In 2015 he received the European Academy of Neurology (EAN) Investigator Award from the Scientific Subspecialty Panel on Neuropathies for his research on gene therapy for inherited neuropathies. He is a selected Member of the European Science Foundation College of Reviewers (2010-2019), and has served as invited reviewer for several research funding organization as well as peer reviewed journals. 
In November 2017 he received the National Distinguished Researcher Award from the Research Promotion Foundation of Cyprus.

 

Selected publications in the last 5 years:

  1. Schiza N, Georgiou E, Kagiava A, Médard JJ, Richter J, Tryfonos C, Sargiannidou I, Heslegrave AJ, Rossor AM, Zetterberg H, Reilly MM, Christodoulou C, Chrast R, Kleopa KA. Gene replacement therapy in a model of Charcot-Marie-Tooth 4C neuropathy. Brain. 2019 May 1;142(5):1227-1241. doi: 10.1093/brain/awz064.
  2.  Papaneophytou CP, Georgiou E, Karaiskos C, Sargiannidou I, Markoullis K, Freidin MM, Abrams CK, Kleopa KA. Regulatory role of oligodendrocyte gap junctions in inflammatory demyelination. Glia. 2018 Dec;66(12):2589-2603. doi: 10.1002/glia.23513. Epub 2018 Oct 16.
  3.  Kagiava A, Kleopa KA. Intrathecal Delivery of Viral Vectors for Gene Therapy. Methods Mol Biol. 2018;1791:277-285. doi: 10.1007/978-1-4939-7862-5_22
  4.  Kagiava A, Karaiskos C, Richter J, Tryfonos C, Lapathitis G, Sargiannidou I, Christodoulou C, Kleopa KA.Intrathecal gene therapy in mouse models expressing CMT1X mutations. Hum Mol Genet. 2018 Apr 15;27(8):1460-1473. doi: 10.1093/hmg/ddy056.
  5. Georgiou E, Sidiropoulou K, Richter J, Papaneophytou C, Sargiannidou I, Kagiava A, von Jonquieres G, Christodoulou C, Klugmann M, Kleopa KA (2017) Gene therapy targeting oligodendrocytes provides therapeutic benefit in a leukodystrophy model, Brain, 140:599-616.
  6. Kyriakoudi S, Sargiannidou I, Kagiava A, Olympiou M, Kleopa KA (2017) Golgi-retained Cx32 mutants interfere with gene addition therapy for CMT1X. Hum Mol Genet. 2017 26:1622-163
  7. Olympiou M, Sargiannidou I, Markoullis K, Karaiskos C, Kagiava A, Kyriakoudi S, Abrams CK, Kleopa KA (2016). Systemic inflammation disrupts oligodendrocyte gap junctions and induces ER stress in a model of CNS manifestations of X-linked Charcot-Marie-Tooth disease. Acta Neuropathol Commun. Sep 1;4(1):95.
  8. Kagiava A, Sargiannidou I, Theophilidis G, Karaiskos C, Richter J, Bashiardes S, Schiza N, Nearchou M, Christodoulou C, Scherer SS, Kleopa KA (2016) Intrathecal gene therapy rescues a model of demyelinating peripheral neuropathy. Proc Natl Acad Sci U S A, 113 (17):e2421-9.
  9. Sargiannidou I, Kagiava A, Bashiardes S, Richter J, Christodoulou C, Scherer SS, Kleopa KA (2015) Intraneural GJB1 gene delivery improves nerve pathology in a model of CMT1X. Annals of Neurology, 78:303-316.
  10. Kagiava A, Theophilidis G, Sargiannidou I, Kyriacou K, Kleopa KA (2015). Oxaliplatin-induced neurotoxicity is mediated through gap junction channels and hemichannels and can be prevented by octanol. Neuropharmacology, 97:289-305.
  11. Markoullis K, Sargiannidou I, Schiza N, Roncaroli F, Reynolds R, Kleopa KA (2014) Oligodendrocyte gap junction loss and disconnection from reactive astrocytes in multiple sclerosis grey matter. J Neuropathol Exp Neurol, 73(9):865-79.
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