Naoko Tanese, PhD

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Professor of Microbiology
Ph.D., 1988 Columbia University

LAB WEBSITE:
Tanese Lab
KEYWORDS:
Transcription, Huntington’s Disease, Polyglutamine Expansion, Embryoid Bodies, Neural Stem Cells, Neuronal Granules, Stress Granules, RNA Transport, Neurodegenerative Disease

Contact Information

NYU School of Medicine
Microbiology, MSB-258
550 First Ave.
New York, NY 10016
Tel: (212) 263-8945
Fax: (212) 263-8276
E-mail: tanesn01@med.nyu.edu
Lab Website: http://www.med.nyu.edu/microbiology-parasitology/faculty/tanese-lab-microbiology


Role of Huntington’s disease protein in ES cells.

 

Huntington’s disease (HD) is a devastating disease that strikes affected individuals in mid-life with symptoms such as motor neuron dysfunction, cognitive and psychiatric disturbances that worsen with age. There is no cure for HD and currently available therapies are of limited use. Better understanding of the functions of the disease-causing huntingtin protein and the pathogenic mechanisms involved in the early stages of HD would permit identification of new targets for therapeutic intervention.

The gene that is mutated in HD is huntingtin (Htt), which encodes a large ubiquitously expressed protein. Expansion of a triplet CAG repeat sequence in the 5’ end of the Htt gene generates a protein with poly-glutamine repeat expansion, which is the cause of HD, an autosomal, dominantly inherited neurodegenerative disorder. Wild-type Htt has been implicated in many cellular functions including regulation of gene expression, endocytosis and microtubule-directed vesicular trafficking in axons and dendrites. Htt is also required for development as Htt null mice die at embryonic day 7.5.

We recently reported a new role for Htt in post-transcriptional gene regulation and maintenance of processing bodies / neuronal RNA granules (PNAS 2008:105,10820; JBC 2010:285,13142). Endogenous Htt was found to co-localize and co-traffic with mRNA in dendrites. An emerging body of evidence suggests regulated transport and local translation of mRNA in neurons play a critical role in establishing their connectivity. Our findings implicate normal Htt in these important dynamic processes in neurons. It is possible that mutant Htt perturbs them in some way, contributing to the HD pathogenesis. Our ongoing research focuses on the identification and characterization of proteins and RNA that associate with normal and mutant Htt. In addition to studying Htt functions in neurons, we are investigating its role in ES cells during differentiation using genomic and proteomic approaches. We are comparing wild-type, Htt null, and ES cells expressing mutant Htt to determine phenotypic and molecular changes that occur when these cells are induced to differentiate into neurons or other cell lineages.

Selected Publications: 

Ma B, Savas JN, Chao MV, Tanese N. (2012) Quantitative analysis of BDNF/TrkB protein and mRNA in cortical and striatal neurons using -tubulin as a normalization factor. Cytometry 81A, 704–17. PMID: 22649026

Culver BP, Savas JN, Park SK, Choi JH, Zheng S, Zeitlin SO, Yates III JR, Tanese N. (2012) Proteomic analysis of wild-type and mutant huntingtin associated proteins in mouse brains identifies unique interactions and involvement in protein synthesis. J. Biol. Chem. 287, 21599-614. PMID: 22556411

Culver BP, Tanese N. (2012). Role of Huntington’s Disease Protein in Post-Transcriptional Gene Regulatory Pathways, Huntington's Disease - Core Concepts and Current Advances, Nagehan Ersoy Tunali (Ed.), ISBN: 978-953-307-953-0

Ma B, Savas JN, Yu M-S, Culver BP, Chao MV, Tanese N. (2011) Huntingtin mediates dendritic transport of β-actin mRNA in rat neurons. Sci. Rep. 1, 140; PMID: 22355657

Savas, J.N., B. Ma, K. Deinhardt, B.P. Culver, S. Restituito, L. Wu, J.G. Belasco, M.V. Chao and N. Tanese. (2010) A role for Huntington’s disease protein in dendritic RNA granules. J. Biol. Chem. 285, 13142-53. PMID: 20185826

Savas, J.N. and N. Tanese. (2010) A combined immunoprecipitation, mass spectrometric, and nucleic acid sequencing approach to determine microRNA-mediated post-transcriptional gene regulatory networks. Brief Funct Genomic Proteomic, 9, 24-31. PMID: 20053813

Ma, B., B.P. Culver, G. Baj, E. Tongiorgi, M.V. Chao and N. Tanese. (2010) Localization of BDNF mRNA with the Huntington’s disease protein in rat brain. Mol. Neurodegener. 5: 22. PMID: 20507609

Jeong, H., F. Then, T.J. Melia, Jr., J.R. Mazzulli, L. Cui, J.N. Savas, C. Voisine, P. Paganetti, N. Tanese, A.C. Hart, A. Yamamoto, D. Krainc. (2009) Acetylation targets mutant huntingtin to autophagosomes for degradation. Cell, 137, 60-72. PMID: 19345187

Savas, J.N., A. Makusky, S. Ottosen, D. Baillat, F. Then, D. Krainc, R. Shiekhattar, S.P. Markey, and N. Tanese. (2008) Huntington’s disease protein contributes to RNA-mediated gene silencing through association with Argonaute and P-bodies. Proc. Natl. Acad. Sci. USA, 105, 10820-5. PMID: 18669659