Naoko Tanese, PhD

Naoko TaneseAssociate Professor of Microbiology
Ph.D., 1988 Columbia University

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/faculty/tanese
Research Theme(s): ES Cell Differentiation, Transcriptional Regulation, RNA Processing, RNA Trafficking Pathways, Neural Stem Cells
Keywords: Huntington’s Disease, Polyglutamine Expansion, Embryoid Bodies, Neural Stem Cells, Transcription, Neuronal Granules, Stress Granules, RNA Transport, Neurodegenerative Disease

Research Summary:

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.

Selected Publications:

 

Regulation of androgen receptor-mediated transcription by RPB5 binding protein URI/RMP.  Mita P, Savas JN, Djouder N, Yates JR 3rd, Ha S, Ruoff R, Schafler ED, Nwachukwu JC, Tanese N, Cowan NJ, Zavadil J, Garabedian MJ, Logan SK.  Mol Cell Biol. 2011 Sep;31(17):3639-52. Epub 2011 Jul 5.  PMID: 21730289 

Target genes of the largest human SWI/SNF complex subunit control cell growth.  Inoue H, Giannakopoulos S, Parkhurst CN, Matsumura T, Kono EA, Furukawa T, Tanese N.  Biochem J. 2011 Feb 15;434(1):83-92.  PMID: 21118156

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

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

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

Acetylation targets mutant huntingtin to autophagosomes for degradation. 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) Cell, 137, 60-72.  PMID: 19345187

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

Transcriptional repression of PGC-1 by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration. Cui L, Jeong H, Borovecki F, Parkhurst CN, Tanese N, Krainc D. (2006) Cell 127, 59-69.  PMID: 17018277