Quantitative isoforrm profiling & isoform convergence

Alternative pre-messenger RNA splicing is a crucial step in eukaryotic gene expression, and therefore it is subject to tight regulation. Given its importance in conferring protein diversity, alternative splicing is sensitive to changes in cellular states including malignancy. We present a new paradigm by which to quantitatively study the alternative splicing of any molecule through the presented methods of quantitative exon profiling and quantitative isoform profiling which take advantage of a single-molecule based technology [Mit99]. Furthermore, we extend this paradigm to include a novel unified platform-called Isoform Convergence-to qualify particular isoforms as candidate diagnostic markers, potential therapeutic targets, and perhaps even as precursor therapeutics themselves. We apply this paradigm to quantitatively investigate the alternative splicing of CD44 in two leukemias. CD44 is an alternatively spliced cell surface receptor, which is generally implicated in cancer though the specifics are mired in controversy. In this work, we suggest several corrections to previously made claims about the presence of specific CD44 exons and of specific CD44 isoforms in leukemia as well as in non-diseased cells.

Department dc:contributor.department

Harvard University--MIT Division of Health Sciences and Technology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2005

Author dc:creator

• Varma, Chris (Chris K.)

Advisor dc:contributor.advisor

• Peter Szolovits and George M. Church.

• Harvard University--MIT Division of Health Sciences and Technology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/33732
• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Identifier URI

http://dspace.mit.edu/handle/1721.1/33732

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/33732