Tanese Lab - Microbiology

Naoko Tanese, Ph.D.
Professor, Department of Microbiology
Associate Dean for Biomedical Sciences
Director, Sackler Institute of Graduate Biomedical Sciences
550 First Avenue
, New York NY 10016
Office: (212) 263-8945
Lab: (212) 263-8957
Email: tanesn01@med.nyu.edu


 

 

KEY INTERESTS:

Huntington’s disease, huntingtin, neurodegenerative disorder, RNA transport, RNA trafficking, dendrite, neuronal granule, argonaute, gene silencing, processing bodies, post-transcriptional gene regulation, transcription, chromatin, SWI/SNF, chromatin remodeling complex, ubiquitin ligase, gene expression, cell cycle, cell growth
 

BIOGRAPHIC DETAILS:

Graduate Education

1988: Ph.D. in Biochemistry and Molecular Biophysics, Columbia University

Postdoctoral Training:

1988-1993: University of California, Berkeley

Academic Appointments:

1993-2000: Assistant Professor
2000-2013: Associate Professor
2013 - :Professor

Major Responsibilities:

Director, Sackler Institute of Graduate Biomedical Sciences

 

RESEARCH INTERESTS:

Post-transcriptional regulation of gene expression by the Huntington’s disease protein huntingtin

Huntington’s disease (HD) is a devastating neurodegenerative 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 (Htt) protein and the pathogenic mechanisms involved in early stages of HD would permit identification of new targets for therapeutic intervention. Expansion of a poly-glutamine sequence in the ubiquitously expressed Htt causes HD. The pathogenic mechanisms of HD remain unclear. Normal Htt has been implicated in many cellular functions including regulation of gene expression, endocytosis and microtubule-directed vesicular trafficking in axons and dendrites.

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 to define their mechanism of action.
 

PUBLICATIONS:

Proteomic Analysis of Wild-type and Mutant Huntingtin-associated Proteins in Mouse Brains Identifies Unique Interactions and Involvement in Protein Synthesis.
Culver BP, Savas JN, Park SK, Choi JH, Zheng S, Zeitlin SO, Yates JR 3rd, Tanese N.
J Biol Chem. 2012 Jun 22;287(26):21599-614.
PMID:22556411

Quantitative analysis of BDNF/TrkB protein and mRNA in cortical and striatal neurons using α-tubulin as a normalization factor.
Ma B, Savas JN, Chao MV, Tanese N.
Cytometry A. 2012 May 30. doi: 10.1002/cyto.a.22073.[Epub ahead of print].
PMID:22649026

Huntingtin mediates dendritic transport of β-actin mRNA in rat neurons.
Ma B, Savas JN, Yu M-S, Culver BP, Chao MV, Tanese N.
Sci. Rep. 2011 Nov 03;1, 140; DOI:10.1038/srep00140.
PMID:22355657

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 Jan 27;434(1):83-92.
PMID:21118156

Mammalian SWI/SNF-A subunit BAF250/ARID1 is an E3 ubiquitin ligase that targets histone H2B.
Li XS, Trojer P, Matsumura T, Treisman JE, Tanese N.
Mol Cell Biol. 2010 Apr;30(7):1673-88.
PMID:20086098

Localization of BDNF mRNA with the Huntington’s disease protein in rat brain.
Ma B, Culver BP, Baj G, Tongiorgi E, Chao MV, Tanese N.
Mol Neurodegener. 2010 May 27;5:22.
PMID:20507609

A role for Huntington’s disease protein in dendritic RNA granules.
Savas JN, Ma B, Deinhardt K, Culver BP, Restituito S, Wu L, Belasco JG, Chao MV, Tanese N.
J Biol Chem. 2010 Apr 23;285(17):13142-53.
PMID:20185826

Huntington’s disease protein contributes to RNA-mediated gene silencing through association with Argonaute and P-bodies.
Savas JN, Makusky A, Ottosen S, Baillat D, Then F, Krainc D, Shiekhattar R, Markey SP, Tanese N.
Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10820-5.
PMID:18669659

A combined immunoprecipitation, mass spectrometric, and nucleic acid sequencing approach to determine microRNA-mediated post-transcriptional gene regulatory networks.
Savas JN, Tanese N.
Brief Funct Genomics. 2010 Jan;9(1):24-31.
PMID:20053813

LAB MEMBERS:

Iryna Berezniuk, Ph.D. – Postdoctoral fellow
Mabel Yu, Ph.D. – Postdoctoral fellow

PROFESSIONAL LINKS:

Sackler Institute of Graduate Biomedical Sciences

 

Visualization of BDNF mRNA with huntingtin and argonaute proteins in the cortex of rat brain
(image taken by Bin Ma).