Glycosaminoglycan regulation of cell function

Glycosaminoglycans (GAGs) are complex polysaccharides that exist both on the cell surface and free within the extracellular matrix. The intrinsic sequence variety stemming from the large number of building blocks that compose this biopolymer leads to substantial information density as well as to the ability to regulate a wide variety of important biological processes. With the recent and progressive emergence of biochemical and analytical tools to probe GAG structure and function, efforts can be taken to understand the role of GAGs in cell biology and in disease in the various physiological locations where GAGs can exist. As a first step to probe the functions of GAGs, the heparin/heparan sulfate-GAG (HSGAG)-fibroblast growth factor (FGF) system was examined. Understanding the role of HSGAGs in inducing FGF2 dimerization led to the development of a novel engineered protein that was found to be effective at promoting functional recovery in stroke. Subsequently, methods to isolate HSGAGs from the cell surface were optimized and the ability of HSGAGs to support FGF signaling was investigated. Cell surface HSGAGs can define the responsiveness of a given cell to FGF1 and FGF2 through multiple receptor isoforms. Stromal cell derived HSGAGs were also identified as critical regulators of tumor cell growth and metastasis, effecting not only FGF2., but also 1-integrin signaling.

Department dc:contributor.department

Massachusetts Institute of Technology. Biological Engineering Division.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2005

Author dc:creator

• Berry, David (David A.)

Advisor dc:contributor.advisor

• Ram Sasisekharan.

• Biological Engineering Division.

Statement dc:rights

• MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission.

Licence dc:rights.uri

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

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/34153

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/34153