2026-09-21T01:45:31Zhttps://dspace.mit.edu/server/oai/requestoai:dspace.mit.edu:1721.1/1067362026-06-17T14:43:47Zcom_1721.1_7582com_1721.1_7581col_1721.1_131022
Richard A. Young.
Reddy, Jessica
Massachusetts Institute of Technology. Department of Biology.
Massachusetts Institute of Technology. Department of Biology
2017-01-30T19:16:05Z
2017-01-30T19:16:05Z
2016
2016
http://hdl.handle.net/1721.1/106736
969341273
Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2016.
Cataloged from PDF version of thesis.
Includes bibliographical references.
Transcription is frequently deregulated in cancer, but targeting of transcriptional processes for cancer therapy has thus far been limited to nuclear receptors. Recent studies, however, have suggested that inhibitors of various general transcriptional regulators can be used in cancer therapy because expression of some oncogenes is disproportionately sensitivity to these inhibitors. Here, I describe the cellular and molecular effects of inhibiting a general transcriptional regulator, CDK7, in T-cell acute lymphoblastic leukemia (T-ALL) cells. Because tumor cells commonly evolve resistance to individual therapies, I have also investigated the potentially synergistic effects of combining two compounds that target transcriptional regulators - the CDK7-inhibitor THZ1 and the BRD4-inhibitor JQ1 - and suggest a model describing the molecular basis of the synergistic effects I observed. My research provides insight into the effects of these inhibitors of general transcriptional regulators on tumor cell behavior and gene expression programs.
by Jessica Reddy.
Ph.D.
155 pages
eng
Massachusetts Institute of Technology
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/1721.1/7582
Biology.
Small-molecule inhibition of general transcriptional regulators in cancer
Thesis
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Publication
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<Abstract>Transcription is frequently deregulated in cancer, but targeting of transcriptional processes for cancer therapy has thus far been limited to nuclear receptors. Recent studies, however, have suggested that inhibitors of various general transcriptional regulators can be used in cancer therapy because expression of some oncogenes is disproportionately sensitivity to these inhibitors. Here, I describe the cellular and molecular effects of inhibiting a general transcriptional regulator, CDK7, in T-cell acute lymphoblastic leukemia (T-ALL) cells. Because tumor cells commonly evolve resistance to individual therapies, I have also investigated the potentially synergistic effects of combining two compounds that target transcriptional regulators - the CDK7-inhibitor THZ1 and the BRD4-inhibitor JQ1 - and suggest a model describing the molecular basis of the synergistic effects I observed. My research provides insight into the effects of these inhibitors of general transcriptional regulators on tumor cell behavior and gene expression programs.</Abstract>
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