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Amy Dubinsky

Mentor: Beverly Davidson, Ph.D.
Lab Room: 200 EMRB
Lab Phone: 319-353-5573

Investigating the functional role of non-coding RNAs in the central nervous system

MicroRNAs (miRNAs) are 18-22 nt long non-coding RNAs that post-transcriptionally regulate gene expression through anti-sense complementarity to sequences in target transcripts. Binding of a miRNA to the 3' untranslated region of an mRNA has been shown to result in translational inhibition and mRNA degradation, providing one mechanism through which cells post-transcriptionally modulate protein and mRNA expression levels. In addition, recent evidence confirms that a single miRNA may be potentially capable of binding to and regulating hundreds of target transcripts, providing evidence for the important role for these molecules in differential regulation of specific, as well as global gene expression.

Given the important role of non-coding RNAs in these and other regulatory events we are interested in determining if miRNA misregulation may contribute to neurodegenerative disease. Our goal is to identify miRNA-mRNA regulatory networks within the central nervous system that may contribute to important cellular functions including: appropriate lineage commitment, establishment and maintenance of gene expression, and cell survival.

Bielekova B, Richert N, Howard T, Packer AN, Blevins G, Ohayon J, McFarland HF, Stürzebecher CS, Martin R. Treatment with the phosphodiesterase type-4 inhibitor rolipram fails to inhibit blood-brain barrier disruption in multiple sclerosis. Mult Scler. 2009 Sep 23. [Epub ahead of print] PMID: 19776093

Dubinsky AN, Burt RK, Martin R, Muraro PA. T-cell clones persisting in the circulation after autologous hematopoietic SCT are undetectable in the peripheral CD34+ selected graft. Bone Marrow Transplant. 2009 Jun 22. [Epub ahead of print] PMID: 19543329

Bielekova B, Howard T, Packer AN, Richert N, Blevins G, Ohayon J, Homas A. Waldmann TA, McFarland HF, Martin R. The anti-CD25 Antibody Daclizumab Inhibits Inflammation and Stabilizes Disease Progression in MS. Arch Neurol; 66 (4):483-9, Apr 2009.

Packer AN, Xing Y, Harper SQ, Jones L, Davidson BL. The bi-functional microRNA miR-9/miR-9* regulates REST and CoREST and is down-regulated in Huntington's Disease. J Neurosci. 2008 Dec 31;28(53):14341-6. PMID: 19118166

Packer AN Muraro PA. Optimized clonotypic analysis of T-cell receptor repertoire in immune reconstitution. Exp Hematol.; 35 (3): 516-21, Mar 2007.

Muraro PA, Cassiani-Ingoni R, Chung K, Packer AN, Sospedra M, Martin R. Clonotypic analysis of cerebrospinal fluid T cells during disease exacerbation and remission in a patient with multiple sclerosis. J Neuroimmunol.; 171 (1-2): 177-83, Feb 2006.

Bielekova B, Catalfamo M, Reichert-Scrivner S, Packer A, Cerna M, Waldmann TA, McFarland H, Henkart PA, Martin R. Regulatory CD56(bright) natural killer cells mediate immunomodulatory effects of IL-2R alpha-targeted therapy (daclizumab) in multiple sclerosis. Proc Natl Acad Sci USA.; 103 (15): 5941-6, Apr 2006.

Muraro PA, Douek DC, Packer A, Chung K, Guenaga FJ, Cassiani-Ingoni R, Campbell C, Memon S, Nagle JW, Hakim FT, Gress RE, McFarland HF, Burt RK, R Martin. Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients. J Exp Med.; 201 (5): 805-16, Mar 2005.