In the last twenty years both computational biology and cancer biology have made great strides and in the last 5 years the merger of the two has helped to revolutionize our knowledge of personalized targeted therapy and the diversity of cancer. In cancer, cell-to-cell interactions between tumor cells and their microenvironment are critical determinants of tumor tissue biology and therapeutic responses. Interactions between glioblastoma (GBM) cells and endothelial cells (ECs) establish a purported stem cell niche. We hypothesized that genes that mediate these interactions would be important, particularly as therapeutic targets. Using a novel computational approach to deconvoluting expression data from mixed physical coculture of GBM cells and ECs, we identified a previously undescribed upregulation of the cAMP specific phosphodiesterase PDE7B in GBM cells in response to ECs. We further found that elevated PDE7B expression occurs in most GBM cases and has a negative effect on survival. PDE7B overexpression resulted in the expansion of a stem-like cell subpopulation, increased tumor aggressiveness, and increased growth in an intracranial GBM model. This deconvolution algorithm provides a new tool for cancer biology, particularly when looking at cell-to-cell interactions, and these results identify PDE7B as a therapeutic target in GBM.
","abstract_html":"<p>In the last twenty years both computational biology and cancer biology have made great strides and in the last 5 years the merger of the two has helped to revolutionize our knowledge of personalized targeted therapy and the diversity of cancer. In cancer, cell-to-cell interactions between tumor cells and their microenvironment are critical determinants of tumor tissue biology and therapeutic responses. Interactions between glioblastoma (GBM) cells and endothelial cells (ECs) establish a purported stem cell niche. We hypothesized that genes that mediate these interactions would be important, particularly as therapeutic targets. Using a novel computational approach to deconvoluting expression data from mixed physical coculture of GBM cells and ECs, we identified a previously undescribed upregulation of the cAMP specific phosphodiesterase PDE7B in GBM cells in response to ECs. We further found that elevated PDE7B expression occurs in most GBM cases and has a negative effect on survival. PDE7B overexpression resulted in the expansion of a stem-like cell subpopulation, increased tumor aggressiveness, and increased growth in an intracranial GBM model. This deconvolution algorithm provides a new tool for cancer biology, particularly when looking at cell-to-cell interactions, and these results identify PDE7B as a therapeutic target in GBM.</p>","abstract_has_math":false,"creators":["Brooks, Michael"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":"Biology and Biomedical Sciences: Molecular Genetics and Genomics","degree_department":null,"school":null,"contributors":["Robi D Mitra"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2014,"date_issued":"2014-01-06T08:00:00Z","date_published":"2014-01-06T08:00:00Z","updated_at":"2026-07-24T06:13:55Z","subjects":["Coculture","Endothelial cells","Glioblastoma","Microenvironment","PDE7B","Transcription"],"languages":["English (en)"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier.doi","label":"DOI","values":["https://doi.org/10.7936/K70K26KZ"],"render_values":[{"text":"https://doi.org/10.7936/K70K26KZ","href":"https://doi.org/10.7936/K70K26KZ","code":true}]}]},"links":{"outbound_url":"https://openscholarship.wustl.edu/etd/1222","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Robi D Mitra"]},{"key":"dc:creator","label":"Author","values":["Brooks, Michael"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2014-06-27T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biology and Biomedical Sciences: Molecular Genetics and Genomics"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Coculture","Endothelial cells","Glioblastoma","Microenvironment","PDE7B","Transcription"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["English (en)"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://openscholarship.wustl.edu/etd/1222"]},{"key":"dc:identifier.doi","label":"DOI","values":["https://doi.org/10.7936/K70K26KZ"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["In the last twenty years both computational biology and cancer biology have made great strides and in the last 5 years the merger of the two has helped to revolutionize our knowledge of personalized targeted therapy and the diversity of cancer. In cancer, cell-to-cell interactions between tumor cells and their microenvironment are critical determinants of tumor tissue biology and therapeutic responses. Interactions between glioblastoma (GBM) cells and endothelial cells (ECs) establish a purported stem cell niche. We hypothesized that genes that mediate these interactions would be important, particularly as therapeutic targets. Using a novel computational approach to deconvoluting expression data from mixed physical coculture of GBM cells and ECs, we identified a previously undescribed upregulation of the cAMP specific phosphodiesterase PDE7B in GBM cells in response to ECs. We further found that elevated PDE7B expression occurs in most GBM cases and has a negative effect on survival. PDE7B overexpression resulted in the expansion of a stem-like cell subpopulation, increased tumor aggressiveness, and increased growth in an intracranial GBM model. This deconvolution algorithm provides a new tool for cancer biology, particularly when looking at cell-to-cell interactions, and these results identify PDE7B as a therapeutic target in GBM.
"]},{"key":"dc:title","label":"Title","values":["Transcriptional Analysis of Reciprocal Tumor-Microenvironment Interactions in Glioblastoma"]}]}],"canonical_facts":{"dc:contributor":["Robi D Mitra"],"dc:creator":["Brooks, Michael"],"dc:date.available":["2014-06-27T07:00:00Z"],"dc:description.abstract":["In the last twenty years both computational biology and cancer biology have made great strides and in the last 5 years the merger of the two has helped to revolutionize our knowledge of personalized targeted therapy and the diversity of cancer. In cancer, cell-to-cell interactions between tumor cells and their microenvironment are critical determinants of tumor tissue biology and therapeutic responses. Interactions between glioblastoma (GBM) cells and endothelial cells (ECs) establish a purported stem cell niche. We hypothesized that genes that mediate these interactions would be important, particularly as therapeutic targets. Using a novel computational approach to deconvoluting expression data from mixed physical coculture of GBM cells and ECs, we identified a previously undescribed upregulation of the cAMP specific phosphodiesterase PDE7B in GBM cells in response to ECs. We further found that elevated PDE7B expression occurs in most GBM cases and has a negative effect on survival. PDE7B overexpression resulted in the expansion of a stem-like cell subpopulation, increased tumor aggressiveness, and increased growth in an intracranial GBM model. This deconvolution algorithm provides a new tool for cancer biology, particularly when looking at cell-to-cell interactions, and these results identify PDE7B as a therapeutic target in GBM.
"],"dc:identifier":["https://openscholarship.wustl.edu/etd/1222"],"dc:identifier.doi":["https://doi.org/10.7936/K70K26KZ"],"dc:language":["English (en)"],"dc:subject":["Coculture","Endothelial cells","Glioblastoma","Microenvironment","PDE7B","Transcription"],"dc:title":["Transcriptional Analysis of Reciprocal Tumor-Microenvironment Interactions in Glioblastoma"],"thesis:degree_discipline":["Biology and Biomedical Sciences: Molecular Genetics and Genomics"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T06:13:55Z"}