Genetic and Molecular Basis of Neurodevelopmental Disorders

Gaia Novarino’s research aims to identify and study genes underlying inherited forms of epilepsy associated with intellectual disability and/or autism. Epilepsy disorders affect millions of people, many of which are children, often refractory to treatments. Epilepsy often presents with intellectual disability and/or autism, suggesting the existence of common molecular mechanisms underlying these syndromes. The causes of epilepsy remain unknown for the majority of cases. Of these, a significant number have a genetic basis and many causative genes remain to be identified. With DNA sequencing being more accessible, the genomes of many patients can be analyzed and more disease-causing genes will be recognized.

Even though we predict that each identified gene may represent only a tiny fraction of the total genes involved in the epilepsies, studying the mechanisms underlying rare inherited forms of seizure syndromes can be extremely helpful. For instance, similarities among the function of genes implicated in epilepsy may point to a smaller number of pathways that are affected among seizure syndromes. The expectation that specific epileptogenic mechanisms may converge into major mechanistic classes predicts that information from rare inherited epilepsies will contribute to the development of broad-spectrum antiepileptic treatments. For this reason, along with a continued search for novel genes, studying the function of epilepsy-causing genes at the system, cellular and molecular levels will provide the framework for the development of effective pharmacological therapies as well as the background for the identification of new pathological genetic variants. In addition, understanding the mechanisms underlying these forms of epilepsy will significantly advance our understanding of the human brain.

Contact

Gaia Novarino
Institute of Science and Technology Austria (IST Austria)
Am Campus 1
A – 3400 Klosterneuburg

Phone: +43 (0)2243 9000-5901
E-mail: gaia.novarino@remove-this.ist.ac.at

CV and Publication List

Novarino Lab website

Assistant

Rita Six

Phone: +43 (0)2243 9000-1165
E-mail: rita.six@remove-this.ist.ac.at

Team

  • Marco Benevento, Predoctoral Visiting Scientist
  • Alberto Coll Manzano, Technician
  • Federica Rachele Danti, PhD Student
  • Elena Deliu, Postdoc
  • Christoph Dotter, PhD Student
  • Jasmin Morandell, PhD Student
  • Roberto Sacco, Postdoc
  • Dora Tarlungeanu, PhD Student
  • Eva Maria Reinthaler, Postdoc

Selected Publications

  • Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder. Tarlungeanu, Dora, Deliu, Elena, Dotter, Christoph P, Kara, Majdi, Janiesch, Philipp C, Scalise, Mariafrancesca, Galluccio, Michele, Tesulov, Mateja, Morelli, Emanuela, Sönmez, Fatma M, Bilgüvar, Kaya, Ohgaki, Ryuichi, Kanai, Yoshikatsu, Johansen, Anide, Esharif, Seham, Ben-Omran, Tawfeg I M, Topcu, Meral F, Schlessinger, Avner, Indiveri, Cesare, Duncan, Kent E, Caglayan, Ahmet O, Günel, Murat, Gleeson, Joseph G, Novarino, Gaia: Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder. In: Cell. Cell Press, 6, 2016,1481-1494.
  • Loss-of-function variants of SETD5 cause intellectual disability and the core phenotype of microdeletion 3p25.3 syndrome. Kuechler A, Zink AM, Wieland T, Lüdecke HJ, Cremer K, Salviati L, Magini P, Najafi K, Zweier C, Czeschik JC, Aretz S, Endele S, Tamburrino F, Pinato C, Clementi M, Gundlach J, Maylahn C, Mazzanti L, Wohlleber E, Schwarzmayr T, Kariminejad R, Schlessinger A, Wieczorek D, Strom TM, Novarino G, Engels H. Eur J Hum Genet. 2015 Jun;23(6):753-60. doi: 10.1038/ejhg.2014.165. Epub 2014 Aug 20.
  • Off-target effect of doublecortin family shRNA on neuronal migration associated with endogenous microRNA dysregulation. Baek ST, Kerjan G, Bielas SL, Lee JE, Fenstermaker AG, Novarino G, Gleeson JG. Neuron. 2014 Jun 18;82(6):1255-62. doi: 10.1016/j.neuron.2014.04.036.
  • Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders. Novarino G, Fenstermaker AG, Zaki MS, Hofree M, Silhavy JL, Heiberg AD, Abdellateef M, Rosti B, Scott E, Mansour L, Masri A, Kayserili H, Al-Aama JY, Abdel-Salam GM, Karminejad A, Kara M, Kara B, Bozorgmehri B, Ben-Omran T, Mojahedi F, Mahmoud IG, Bouslam N, Bouhouche A, Benomar A, Hanein S, Raymond L, Forlani S, Mascaro M, Selim L, Shehata N, Al-Allawi N, Bindu PS, Azam M, Gunel M, Caglayan A, Bilguvar K, Tolun A, Issa MY, Schroth J, Spencer EG, Rosti RO, Akizu N, Vaux KK, Johansen A, Koh AA, Megahed H, Durr A, Brice A, Stevanin G, Gabriel SB, Ideker T, Gleeson JG. Science. 2014 Jan 31;343(6170):506-11. doi: 10.1126/science.1247363.
  • The sacred disease: the puzzling genetics of epileptic disorders.Novarino G, Baek ST, Gleeson JG.
    Neuron. 2013 Oct 2;80(1):9-11. doi: 10.1016/j.neuron.2013.09.019. Epub 2013 Oct 2.
  • Mutations in the BCKD-kinase lead to a potentially treatable form of autism with epilepsy. Novarino G*, El-Fishawy P, Kayserili H, Meguid NA. , Scott ES., Schroth J, Silhavy JL., Kara M, Khalil RO., Ben-Omran T, Ercan-Sencicek A.G, Hashish AF., Sanders SJ., Gupta AR., Hashem HS., Matern D, Gabriel S, Sweetman L, Rahimi Y, Harris RA., State MW and Gleeson JG.*, Science 2012 Oct 19;338(6105): 394-397. (*Corresponding authors)
  • Exome Sequencing Can Improve Diagnosis and Alter Patient Management. Dixon-Salazar TJ., Silhavy JL., Udpa N, Schroth J, Bielas S, Schaffer AE., Olvera J, Bafna V, Zaki MS., Abdel-Salam GH, Mansour LA., Selim L, Abdel-Hadi S, Marzouki N, Ben-Omran T, Al-Saana NA., Sonmez FM., Celep F, Azam M, Hill KJ., Collazo A, Fenstermaker AG., Novarino G, Akizu N, Garimella KV., Sougnez C, Russ C, Gabriel SB. and Gleeson JG., Science Translational Medicine 2012 June 13; 138(4).
  • Modeling human disease in humans: the ciliopathies. Novarino G, Akizu N, Gleeson JG., Cell 2011 Sep 30;147(1):70-9.

Career

2014 Assistant Professor, IST Austria
2010–2013 Postdoc UCSD, La Jolla-California (Joseph Gleeson Lab)
2006–2010 Postdoc ZMNH (Center for Molecular Neurobiology
Hamburg), Hamburg-Germany and MDC/FMP Berlin-Germany (Thomas Jentsch Lab)
2006 PhD in Cell Biology, University “La Sapienza”, Rome-Italy

Selected Distinctions

2016 Simons Foundation Autism Research Initiative (SFARI) Investigator
2016 ERC Starting Grant
2015 Boehringer Ingelheim FENS Research Award 2016
2015 Citizens United for Research in Epilepsy (CURE): Taking Flight Award
2012 Citizens United for Research in Epilepsy (CURE): Young Investigator Travel Award
2011 German Research Foundation (DFG): 2-year fellowship

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