Prof. Illana Gozes

גנטיקה מולקולרית של אדם וביוכימיה אמריטוס
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Phone: 03-6407240
Another phone: 03-6405809
Fax: 03-6408541
עמוד חוקר בפקולטה לרפואה
Office: Sackler School of Medicine, 727

Positions

Professor Emerita of Clinical Biochemistry, Sackler Faculty of Medicine
 
Lily and Avraham Gildor Chair for the Investigation of Growth Factors
 
Director, Dr. Diana and Zelman Elton Laboratory for Molecular Neuroendocrinology
 
Editor-in-Chief, Journal of Molecular Neuroscience
 
Member, The Council for Higher Education (CHE), Israel
 
Chief Scientific Officer, Coronis Neuroscience
 
Council Member, European Society for Neurochemistry
 
President Summer Neuropeptide Conference

Research

Neuronal Plasticity and Nerve Cell Protection in Disease

Our research is characterized by a multi-level approach to the study of brain function, behavior, memory and drug discovery, from molecules to cures. Targeting autism, schizophrenia as well as Alzheimer’s disease and related neurodegeneration and utilizing a multidisciplinary approach, our group investigates different aspects of neuronal plasticity and nerve cell protection, at the molecular, cellular and system level. 

 

A major focus in the laboratory is on nerve structure and transport mechanisms. We have discovered novel families of proteins associated with cross talk among nerve cells and their support cells, including activity-dependent neurotrophic factor (ADNF) and activity-dependent neuroprotetive proteins (ADNPs, with ADNP being a major gene mutated in autism). Small ADNF and ADNP derivatives are in clinical development. The lead compound, davunetide is planned for an advanced Phase II clinical trial with the biotech industry.

 

Davunetide has previously shown efficacy in several Phase II clinical trials (i.e. in patients suffering from mild cognitive impairment, preceding Alzheimer's disease and in schizophrenia patients, protecting activities of daily living).

 

Publications & Grants

Publications

 

218. A.R. Esteves, I. Gozes, and S.M. Cardoso. The rescue of microtubule-dependent traffic recovers mitochondrial function in Parkinson's disease. Biochim Biophys Acta. . 2014, 1842:7-21.
 
219. I. Gozes Y. Schirer, A. Idan-Feldman, M. David, S. Furman-Assaf. NAP Alpha-Aminoisobutyric Acid (IsoNAP). J Mol Neurosci. 2014:52 (1):1-9.
 
220. Gozes I, Iram T, Maryanovsky E, Arviv C, Rozenberg L, Schirer Y, Giladi  E, Furman-Assaf, S. Novel tubulin and tau neuroprotective fragments sharing structural similarities with the drug candidate NAP (davuentide). J Alzheimers Dis. 2014;40 Suppl 1:S23-36
 
221. Schirer Y, Malishkevich A, Ophir Y, Lewis J, Giladi E, Gozes I. A novel marker for the onset of frontotemporal dementia: early increase in activity-dependent neuroprotective protein (ADNP) in the face of tau mutation. PLoS One. 2014 Jan 29;9(1):e87383. doi: 10.1371/journal.pone.0087383. eCollection 2014.
 
222. Boxer AL, Lang AE, Grossman M, Knopman DS, Miller BL, Schneider LS, Doody RS, Lees A, Golbe LI, Williams DR, Corvol JC, Ludolph A, Burn D, Lorenzl S, Litvan I, Roberson ED, Hoglinger GU, Koestler M, Jack CR, Jr., Van Deerlin V, Randolph C, Lobach IV, Heuer HW, Gozes I, Parker L, Whitaker S, Hirman J, Stewart AJ, Gold M, Morimoto BH. Davunetide in patients with progressive supranuclear palsy: a randomised, double-blind, placebo-controlled phase 2/3 trial. Lancet Neurol. 2014; 13:676-685
 
223. Magen I, Ostritsky R, Richter F, Zhu C, Fleming SM, Lemesre V, Stewart AJ, Morimoto BH, Gozes I, Chesselet MF. Intranasal NAP (Davunetide) decreases tau hyperphosphorylation and moderately improves behavioral deficits in mice over-expressing alpha-synuclein. Pharmacology Research & Perspectives. 2014; 2 (5) DOI: 10.1002/prp2.65
 
224. S. Oz, O. Kapitansky, Y. Ivashco-Pachima, A. Malishkevich, E. Giladi, N. Skalka, R. Rosin-Arbesfeld, L. Mittelman, O. Segev, J.A. Hirsch, I. Gozes. The NAP Motif in Activity-Dependent Neuroprotective Protein Regulates Dendritic Spines by Interaction with Microtubule End Binding Proteins. Mol Psychiatry. 2014 Oct;19(10):1115-24. doi: 10.1038/mp.2014.97. Epub 2014 Sep 2.
Cover picture.
 
225. V.V. Korolkov, S. Allen, C.J. Roberts, I. Gozes, S. J. Tendler. Study of NAP adsorption and assembly on the surface of HOPG. Peptides. 2014 Dec;62:55-8. doi: 10.1016/j.peptides.2014.09.017. Epub 2014 Sep 30
 
226. A. Merenlender-Wagner, Z. Shemer, O. Touloumi, R. Lagoudaki, E. Giladi, A. Andrieux, N. Grigoriadis, I. Gozes: New horizons in schizophrenia: autophagy protection is coupled to behavioral improvements in a mouse model of schizophrenia, Autophagy. 2014 Dec 2;10(12):2324-32. doi: 10.4161/15548627.2014.984274.
 
227. I. Gozes, A. Yeheskel, M. Pasmanik-Chor. Activity-Dependent Neuroprotective Protein (ADNP): A Case Study for Highly Conserved Chordata-Specific Genes Shaping the Brain and Mutated in Cancer. J Alzheimers Dis. 2015 Jan 1;45(1):57-73. doi: 10.3233/JAD-142490.
 
228. A. Merenlender-Wagner, A. Malishkevich, Z. Shemer, M. Udawela, A. Gibbons, E. Scarr, B. Dean, G. Agam, I. Gozes. Autophagy plays a key role in the pathophysiology of schizophrenia. Mol Psychiatry. 2015 Feb;20(1):126-32. doi: 10.1038/mp.2013.174. Epub 2013 Dec 24.
 
229. A Malishkevich, N. Amram, G. Hacohen Kleiman, I. Magen, E. Giladi, I. Gozes. Activity-Dependent Neuroprotective Protein (ADNP) Exhibits Striking Sexual Dichotomy Impacting on Autistic and Alzheimer's Pathologies. Transl Psychiatry. 2015 Feb 3;5:e501. doi: 10.1038/tp.2014.138.
 
230. G. Hacohen Kleiman, A, Barnea, I. Gozes. ADNP: A major autism mutated gene is differentially distributed (age and gender) in the songbird brain. Peptides 2015, 72:75-79.
 
231. A. Malishkevich, J. Leyk, O. Goldbaum, C. Richter-Landsberg, I. Gozes. 2015 ADNP/ADNP2 expression in oligodendrocytes: implication for myelin-related neurodevelopment.  J Mol Neurosci. 2015 Oct;57(2):304-13. doi: 10.1007/s12031-015-0640-4
 
232. S. Vaisburd, Z. Shemer, A. Yeheskel, E. Giladi, I. Gozes, I. Risperidone and NAP protect cognition and normalize gene expression in a schizophrenia mouse model. Sci Rep 2015, 5:16300.
 
233. M.M. Heimesaat, A. Fischer, A.A. Kuhl, U.B. Gobel, I. Gozes, S. Bereswill, Anti-Inflammatory Properties of NAP in Acute Toxoplasma Gondii-Induced Ileitis in Mice. Eur J Microbiol Immunol (Bp) 2015, 5:210-220.
 
234. A. Malishkevich, G.A. Marshall, A.P. Schultz, R.A. Sperling, J. Aharon-Peretz, I. Gozes. Blood-Borne Activity-Dependent Neuroprotective Protein (ADNP) is Correlated with Premorbid Intelligence, Clinical Stage, and Alzheimer's Disease Biomarkers. J Alzheimers Dis. 2016;50(1):249-60. doi: 10.3233/JAD-150799.http://www.ncbi.nlm.nih.gov/pubmed/26639975
 
235. Amram, N.*, Hacohen-Kleiman, G.*, Sragovich, S., Malishkevich, A., Katz, J., Touloumi, O., Lagoudaki, R., Grigoriadis, N., Giladi, E., Yeheskel, A., Pasmanik-Chor, M., Jouroukhin, Y., Gozes, I. Sexual Divergence in Microtubule Function: The Novel Intranasal Microtubule Targeting SKIP Normalizes Axonal Transport and Enhances Memory. Mol Psychiatry. 2016 Oct;21(10):1467-76. doi: 10.1038/mp.2015.208. (*equal contribution)
 
236. Gozes, I., Sragovich, S., Schirer, Y., Idan-Feldman, A. D-SAL and NAP: Two Peptides Sharing a SIP Domain. J Mol Neurosci. 2016 Jun;59(2):220-31. http://www.ncbi.nlm.nih.gov/pubmed/26816081
 
237. Hadar A, Milanesi E, Squassina A, Niola P, Chillotti C, Pasmanik-Chor M, Yaron O, Martásek P, Rehavi M, Weissglas-Volkov D, Shomron N, Gozes I*, Gurwitz D*. RGS2 expression predicts amyloid-β sensitivity, MCI and Alzheimer's disease: genome-wide transcriptomic profiling and bioinformatics data mining Trans Psychiatry. 2016 Oct 4;6(10):e909. doi: 10.1038/tp.2016.179. https://www.ncbi.nlm.nih.gov/pubmed/27701409 (*Co-corresponding authors)
 
238. Polanco MJ, Parodi S, Piol D, Stack C, Chivet M, Contestabile A, Miranda HC, Lievens PM-J, Espinoza S, Jochum T, Rocchi A, Grunseich C, Gainetdinov RR, Cato ACB, Lieberman AP, La Spada AR, Sambataro F, Fischbeck KH, Gozes I, Pennuto M (2016) Adenylyl cyclase activating polypeptide reduces phosphorylation and toxicity of the polyglutamine-expanded androgen receptor in spinobulbar muscular atrophy. Sci Transl Med. 2016 Dec 21;8(370):370ra181. doi: 10.1126/scitranslmed.aaf9526. https://www.ncbi.nlm.nih.gov/pubmed/28003546
 
239. Ivashko-Pachima, Y. Sayas, CL, Malishkevich A. and Gozes, I. ADNP/NAP dramatically increase microtubule end binding protein-Tau interaction: A novel avenue for protection against tauopathy. Mol Psychiatry. 2017 Sep;22(9):1335-1344. EPUB Jan 24. doi: 10.1038/mp.2016.255. https://www.ncbi.nlm.nih.gov/pubmed/28115743
 
240. Gozes I, Van Dijck A, Hacohen-Kleiman G, Grigg I, Karmon G, Giladi E, Eger M, Gabet Y, Pasmanik-Chor M, Cappuyns E, Elpeleg O, Kooy RF, Bedrosian-Sermone S. Premature primary tooth eruption in cognitive/motor-delayed ADNP-mutated children. Transl Psychiatry. 2017 Feb 21;7(2):e1043. doi: 10.1038/tp.2017.27. https://www.ncbi.nlm.nih.gov/pubmed/28221363
 
241. Gozes I., Patterson MC, Van Dijck A, Kooy RF, Peeden JN, Eichenberger JA, Zawacki-Downing A, Bedrosian-Sermone S. The Eight and a Half Year Journey of Undiagnosed AD: Gene Sequencing and Funding of Advanced Genetic Testing Has Led to Hope and New Beginnings. Front. Endocrinol., 19 May 2017 | https://doi.org/10.3389/fendo.2017.00107 http://journal.frontiersin.org/article/10.3389/fendo.2017.00107/full
 
242. Rojas JC, Bang J, Lobach IV, Tsai RM, Rabinovici GD, Miller BL, Boxer AL; AL-108-231 Investigators. CSF neurofilament light chain and phosphorylated tau 181 predict disease progression in PSP. Neurology. 2018 Jan 23;90(4):e273-e281. doi: 10.1212/WNL.0000000000004859. Epub 2017 Dec 27.https://www.ncbi.nlm.nih.gov/pubmed/29282336
 
243. Heimesaat MM, Giladi E, Kühl AA, Bereswill S, Gozes I. The octapetide NAP alleviates intestinal and extra-intestinal anti-inflammatory sequelae of acute experimental colitis Peptides. 2018 Mar;101:1-9. doi: 10.1016/j.peptides.2017.12.023. Epub 2017 Dec 27. https://www.ncbi.nlm.nih.gov/pubmed/29288684
 
244. Van Dijck A, Vulto-van Silfhout AT, Cappuyns E, van der Werf IM, Mancini GM, Tzschach A, Bernier R, Gozes I, Eichler EE, Romano C, Lindstrand A, Nordgren A; ADNP Consortium, Kvarnung M, Kleefstra T, de Vries BBA, Küry S, Rosenfeld JA, Meuwissen ME, Vandeweyer G, Kooy RF. Clinical Presentation of a Complex Neurodevelopmental Disorder Caused by Mutations in ADNP. Biol Psychiatry. 2019 Feb 15;85(4):287-297. doi: 10.1016/j.biopsych.2018.02.1173. Epub 2018 Mar 15 http://www.biologicalpsychiatryjournal.com/article/S0006-3223(18)31303-9/fulltext
 
245. Hadar A, Milanesi E, Walczak M, Puzianowska-Kuźnicka M, Kuźnicki J, Squassina A, Niola P, Chillotti C, Attems J, Gozes I, Gurwitz D. SIRT1, miR-132 and miR-212 link human longevity to Alzheimer's Disease. Sci Rep. 2018 May 31;8(1):8465. doi: 10.1038/s41598-018-26547-6. https://www.ncbi.nlm.nih.gov/pubmed/29855513
 
246. Escher U, Giladi E, Dunay IR, Bereswill S, Gozes I, Heimesaat MM. Anti-inflammatory Effects of the Octapeptide NAP in Human Microbiota-Associated Mice Suffering from Subacute Ileitis. Eur J Microbiol Immunol (Bp). 2018 May 23;8(2):34-40. doi: 10.1556/1886.2018.00006. eCollection 2018 Jun 25.https://www.ncbi.nlm.nih.gov/pubmed/29997909
 
247. Ziv Y, Rahamim N, Lezmy N, Even-Chen O, Shaham O, Malishkevich A, Giladi E, Elkon R, Gozes I, Barak S.
Activity-dependent neuroprotective protein (ADNP) is an alcohol-responsive gene and negative regulator of alcohol consumption in female mice. Neuropsychopharmacology. 2019 Jan;44(2):415-424. doi: 10.1038/s41386-018-0132-7. Epub 2018 Jun 27. https://www.ncbi.nlm.nih.gov/pubmed/30008470
 
248. Hacohen-Kleiman G, Sragovich S, Karmon G, Gao AYL, Grigg I, Pasmanik-Chor M, Le A, Korenková V, McKinney RA, Gozes I. Activity-dependent neuroprotective protein deficiency models synaptic and developmental phenotypes of autism-like syndrome. J Clin Invest. 2018;128(11):4956-69. https://www.ncbi.nlm.nih.gov/pubmed/30106381
 
249. Ivashko-Pachima Y, Gozes I. NAP protects against Tau hyperphosphorylation through GSK3. Curr Pharm Des. 2018;24(33):3868-3877. doi: 10.2174/1381612824666181112105954https://www.ncbi.nlm.nih.gov/pubmed/30417779
 
250. Brittain C, McCarthy A, Irizarry MC, McDermott D, Biglan K, Höglinger GU, Lorenzl S, Del Ser T, Boxer AL; AL-108-231 Study Group; PROPSPERA investigators; 4RNTI-1authors; Tau Restoration on PSP (TAUROS) Investigators.
Severity dependent distribution of impairments in PSP and CBS: Interactive visualizations. Parkinsonism Relat Disord. 2018 Sep 4. pii: S1353-8020(18)30384-5. doi: 10.1016/j.parkreldis.2018.08.025. [Epub ahead of print]https://www.ncbi.nlm.nih.gov/pubmed/30201421
 
251. Hacohen-Kleiman G, Yizhar-Barnea O, Touloumi O, Lagoudaki R, Avraham KB, Grigoriadis N, Gozes I.
Atypical Auditory Brainstem Response and Protein Expression Aberrations Related to ASD and Hearing Loss in the Adnp Haploinsufficient Mouse Brain. Neurochem Res. 2019 Jan 18. doi: 10.1007/s11064-019-02723-6. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30659505
 
252. Sragovich S, Malishkevich A, Piontkewitz Y, Giladi E, Touloumi O, Lagoudaki R, Grigoriadis N, Gozes I.
The autism/neuroprotection-linked ADNP/NAP regulate the excitatory glutamatergic synapse. Transl Psychiatry. 2019 Jan 15;9(1):2. doi: 10.1038/s41398-018-0357-6. https://www.ncbi.nlm.nih.gov/pubmed/30664622
 
253. Mollinedo P, Kapitansky O, Gonzalez-Lamuño D, Zaslavsky A, Real P, Gozes I, Gandarillas A, Fernandez-Luna JL.
Cellular and animal models of skin alterations in the autism-related ADNP syndrome. Sci Rep. 2019 Jan 24;9(1):736. doi: 10.1038/s***************-2. https://www.ncbi.nlm.nih.gov/pubmed/30679581
 
254. In press – online: Reduction of aluminum ion neurotoxicity through a small peptide application – NAP treatment of Alzheimer's disease - https://www.sciencedirect.com/science/article/pii/S1021949819300109

 

Reviews

 

87. I. Gozes. The cytoskeleton as a drug target for neuroprotection: the case of the autism-mutated ADNP. Biol Chem. 2016 Mar;397(3):177-84. http://www.ncbi.nlm.nih.gov/pubmed/25955282
 
88. I. Gozes, C. Helsmoortel, G. Vandeweyer, N. Van der Aa, F. Kooy, S. Bedrosian Sermone. The Compassionate Side of Neuroscience: Tony Sermone Undiagnosed Genetic Journey—ADNP Mutation. J Mol Neurosci (2015) 56:751–757. DOI 10.1007/s12031-015-0586-6. http://www.ncbi.nlm.nih.gov/pubmed/25955282
 
89. I. Gozes, P.W. Baas, C. Richter-Landsberg. International Meeting Molecular Neurodegeneration: News and Views in Molecular Neuroscience in Health and Disease. Delmenhorst, Germany, July 20–22, 2015. J Mol Neurosci. 2015 Oct;57(2):153-9. doi: 10.1007/s12031-015-0637-z. http://www.ncbi.nlm.nih.gov/pubmed/26319265
 
90. I. Gozes, Y. Ivashko-Pachima, ADNP: in search for molecular mechanisms and innovative therapeutic strategies for frontotemporal degeneration. Front Aging Neurosci 2015, 7:205.http://www.ncbi.nlm.nih.gov/pubmed/26578950
 
91. D.J. Klionsky, …I. Gozes (~1000 authors). Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 2016 Jan 2;12(1):1-222. http://www.ncbi.nlm.nih.gov/pubmed/26799652
 
92. Pennuto M, I. Gozes. Introduction to the Special Issue on Spinal and Bulbar Muscular Atrophy. J Mol Neurosci. 2016 Mar;58(3):313-6. http://www.ncbi.nlm.nih.gov/pubmed/26875173
 
93. Y. Ivashko-Pachima, L.Y. Zhou, P. Lei, I. Gozes.  Microtubule-Tau Interaction as a Therapeutic Target for Alzheimer's Disease. J Mol Neurosci. 2016 Feb;58(2):145-52. doi: 10.1007/s12031-016-0715-x.http://www.ncbi.nlm.nih.gov/pubmed/26816082
 
94. Gozes I. The Future for Dementia Research: a Perspective from the Journal of Molecular Neuroscience. J Mol Neurosci. 2016 Nov;60(3):410-411. https://www.ncbi.nlm.nih.gov/pubmed/27647306
 
95. Dutt S, Binney RJ, Heuer HW, Luong P, Attygalle S, Bhatt P, Marx GA, Elofson J, Tartaglia MC, Litvan I, McGinnis SM, Dickerson BC, Kornak J, Waltzman D, Voltarelli L, Schuff N, Rabinovici GD, Kramer JH, Jack CR Jr, Miller BL, Rosen HJ, Boxer AL; AL-108-231 investigators (including Gozes I). Progression of brain atrophy in PSP and CBS over 6 months and 1 year. Neurology. 2016 Nov 8;87(19):2016- 2025.https://www.ncbi.nlm.nih.gov/pubmed/27742814
 
96. Gozes I. PACAP, VIP, and ADNP: Autism and Schizophrenia. In: Pituitary Adenylate Cyclase Activating Polypeptide (Dora Reglodi and Andrea Tamas, Editors, Current Topics in Neurotoxicity 11, Springer) 2016 pp. 781-792.
 
97. Gozes I. Sexual divergence in activity-dependent neuroprotective protein impacting autism, schizophrenia, and Alzheimer's disease. J Neurosci Res. 2017 Jan 2;95(1-2):652-660. https://www.ncbi.nlm.nih.gov/pubmed/27870441
 
98. S. Sragovich, A. Merenlender-Wagner, and I. Gozes, ADNP Plays a Key Role in Autophagy: From Autism to Schizophrenia and Alzheimer's Disease. BioEssays : news and reviews in molecular, cellular and developmental biology 39 (2017).
 
99. I. Gozes, G. Hoglinger, J.P. Quinn, N.M. Hooper, and K. Hoglund, Tau Diagnostics and Clinical Studies. Journal of molecular neuroscience : MN 63 (2017) 123-130. https://www.ncbi.nlm.nih.gov/pubmed/29082468
 
100. I. Gozes, Specific protein biomarker patterns for Alzheimer's disease: improved diagnostics in progress. EPMA J 8 (2017) 255 - 259. https://www.ncbi.nlm.nih.gov/pubmed/29021836https://www.ncbi.nlm.nih.gov/pubmed/28940660
 
101. Gozes I, Ivashko-Pachima Y, Sayas CL. ADNP, a Microtubule Interacting Protein, Provides Neuroprotection Through End Binding Proteins and Tau: An Amplifier Effect. Front Mol Neurosci. 2018 May 1;11:151. doi: 10.3389/fnmol.2018.00151. eCollection 2018. https://www.frontiersin.org/articles/10.3389/fnmol.2018.00151/full
 
 
103. Dardiotis E, Aloizou AM, Markoula S, Siokas V, Tsarouhas K, Tzanakakis G, Libra M, Kyritsis AP, Brotis AG, Aschner M, Gozes I, Bogdanos DP, Spandidos DA, Mitsias PD, Tsatsakis A. Cancer-associated stroke: Pathophysiology, detection and management (Review) Int J Oncol. 2019 Mar;54(3):779-796. doi: 10.3892/ijo.2019.4669. Epub 2019 Jan 2. https://www.ncbi.nlm.nih.gov/pubmed/30628661
 
104. Shioda S, Gozes I. Neuropeptides: From Bench to Bedside. Curr Pharm Des. 2018;24(33):3867. doi: 10.2174/138161282433190109122611. https://www.ncbi.nlm.nih.gov/pubmed/30693852

 

Books

 

 

Grants

 

2016-2019       Ministry of Science and Technology, Israel, Eshkol Fellowships (Shlomo Sragovich, Gal Hacohen Kleiman, student fellowships)

 

2017-2020       NSF-BSF (US-Israel BiNational Science Foundation) - Computational Approaches to Assess Replicability of Neurobehavioral (~$32000, direct with three partners, including Prof. Yoav Benjamini and Professor Ilan Golani and Jackson Labs.)

 

2019-2020       Ministry of Defense Israel, Science Unit, Brain trauma biomarkers

 

2019-2022       ERA-NET Neuron, he pleiotropic effects of ADNP in Mental Disorders (Ministry of Health)

 

2008-               A.M.N. Foundation

 

Donations:       Drs. Ronith and Armand Stemmer, Mr Arthur Gerbi (French Friends of Tel Aviv University), and Spanish Friends of Tel Aviv University, Ms. Alicia Koplowitz

 

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