رسالة جامعية

Modulating cell behavior with engineered HER-receptor ligands

التفاصيل البيبلوغرافية
العنوان: Modulating cell behavior with engineered HER-receptor ligands
المؤلفون: Alvarez, Luis M. (Luis Manuel)
المساهمون: Linda G. Griffith and Richard T. Lee., Massachusetts Institute of Technology. Dept. of Biological Engineering.
بيانات النشر: Massachusetts Institute of Technology
سنة النشر: 2009
المجموعة: DSpace@MIT (Massachusetts Institute of Technology)
مصطلحات موضوعية: Biological Engineering
الوصف: Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biological Engineering, September 2009. ; "August 2009." Cataloged from PDF version of thesis. ; Includes bibliographical references. ; The primary motivation for this work is the manipulation of EGFR family signaling to influence regenerative responses of mesenchymal stem cells (MSC). Underlying the potential of regenerative medicine is the need to understand and control cell behavior. A 'cue, signal, response' paradigm has emerged as a framework for building predictive models for manipulation of cells to achieve desired responses. The HER receptor tyrosine kinase (RTK) family is an attractive target for manipulation of cues and signals, as its four members - epidermal growth factor receptor (EGFR or HERI), HER2, HER3 and HER4 - influence processes as diverse as development, wound healing, migration, and tissue homeostasis and family members are expressed by almost every cell type. All HER receptors require either homodimerization or heterodimerization with other family members for activation of signaling pathways, and the various dimer pairs are not equivalent in their ability to activate all the downstream pathways. Hence, signaling (and phenotypic) outcomes may be dictated not only by the number (or fraction) of each type of receptor ligated, but by the quantitative distribution of these receptors into various possible dimer pairs. The canonical physiological ligands for the HER family receptors are monomeric, allowing occupied receptors to freely homodimerize or heterodimerize. The premise of this work is that engineered bivalent ligands can drive specific dimerization events to enhance or inhibit signaling by various HER family receptors in a quantitative fashion that might be predicted on the basis of receptor expression. This work focuses on the design and implementation of engineered protein systems that are targeted to control homo and heterodimerization of HERI and HER3. One broad consequence of using homodimer ligands is to ...
نوع الوثيقة: thesis
وصف الملف: 130 p.; application/pdf
اللغة: English
العلاقة: http://hdl.handle.net/1721.1/62985Test; 720385384
الإتاحة: http://hdl.handle.net/1721.1/62985Test
حقوق: 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. ; http://dspace.mit.edu/handle/1721.1/7582Test
رقم الانضمام: edsbas.4DDB2B43
قاعدة البيانات: BASE