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You searched for +publisher:"University of North Carolina" +contributor:("Cooper, Matthew James"). One record found.

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University of North Carolina

1. Cooper, Matthew James. Kinome Profiling of Drug-Resistant Myeloid Leukemia to Guide the Use of Targeted Therapy.

Degree: 2013, University of North Carolina

Protein kinases are key mediators of cellular signaling. Consequently, dysregulated kinases are central to cancer initiation, progression and acquired drug resistance, and are a major focus in the development of targeted cancer therapies. IKKα, is often involved in oncogenic initiation and progression through its role in activating the transcription factor NF-κB. However, depending on the context it may function as a tumor suppressor. This concept has been demonstrated here. Chapter 2 discusses work exploring the functional relationship between IKKα and the androgen receptor (AR) in prostate cancer cells. It is shown that IKKα and AR physically interact, that IKKα overexpression attenuates AR activity and that, conversely, IKKα ablation results in increased AR activity. IKKα phosphorylates AR at Ser29, and mutation of this site causes AR to be refractory to IKKα inhibition. These results indicate a previously unreported role for IKKα as a tumor suppressor in prostate cancer. Chapter 3 discusses work using novel multiplexed kinase inhibitor beads (MIBs) coupled with quantitative mass spectrometry (MS) to compare the kinase expression and activity of a Lyn-driven imatinib-resistant cell line, MYL-R, and its imatinib-sensitive counterpart, MYL. Expression and activity changes of 153 kinases were measured from various protein kinase families, and statistical analysis identified 35 kinases with significant differences, referred to as the MYL-R kinome profile. MIB/MS and immunoblot analysis confirmed the over-expression and activation of Lyn in MYL-R cells and identified additional kinases with increased (e.g., MEK, ERK, IKKα, PKCβ, NEK9) or decreased (e.g., Abl, Kit, JNK, ATM, Yes) abundance or activity. Pharmacological and shRNA-mediated Lyn inhibition reduced MEK and IKKα phosphorylation. MYL-R cells showed elevated NF-κB signaling relative to MYL cells, so the effects of the IKK inhibitor, BAY 65-1942 (BAY), were tested. Further MIB/MS analysis revealed that BAY increased MEK/ERK signaling, which was prevented by co-treatment with a MEK inhibitor (AZD6244). The combined inhibition of IKKα and MEK resulted in synergistic loss of cell viability, leading to apoptosis. These results demonstrate the utility of MIB/MS as a tool to identify dysregulated kinases and to interrogate kinome dynamics as cells respond to targeted kinase inhibition. Advisors/Committee Members: Cooper, Matthew James, Baldwin, Albert, University of North Carolina at Chapel Hill.

Subjects/Keywords: School of Medicine; Curriculum in Genetics and Molecular Biology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Cooper, M. J. (2013). Kinome Profiling of Drug-Resistant Myeloid Leukemia to Guide the Use of Targeted Therapy. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:39c80d6c-0cfd-494d-96b1-aea19c48ea22

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Cooper, Matthew James. “Kinome Profiling of Drug-Resistant Myeloid Leukemia to Guide the Use of Targeted Therapy.” 2013. Thesis, University of North Carolina. Accessed September 27, 2020. https://cdr.lib.unc.edu/record/uuid:39c80d6c-0cfd-494d-96b1-aea19c48ea22.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Cooper, Matthew James. “Kinome Profiling of Drug-Resistant Myeloid Leukemia to Guide the Use of Targeted Therapy.” 2013. Web. 27 Sep 2020.

Vancouver:

Cooper MJ. Kinome Profiling of Drug-Resistant Myeloid Leukemia to Guide the Use of Targeted Therapy. [Internet] [Thesis]. University of North Carolina; 2013. [cited 2020 Sep 27]. Available from: https://cdr.lib.unc.edu/record/uuid:39c80d6c-0cfd-494d-96b1-aea19c48ea22.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Cooper MJ. Kinome Profiling of Drug-Resistant Myeloid Leukemia to Guide the Use of Targeted Therapy. [Thesis]. University of North Carolina; 2013. Available from: https://cdr.lib.unc.edu/record/uuid:39c80d6c-0cfd-494d-96b1-aea19c48ea22

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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