Person: Martuza, Robert
Email Address
AA Acceptance Date
Birth Date
Research Projects
Organizational Units
Job Title
Last Name
First Name
Name
Search Results
Publication Reconstructing and Reprogramming the Tumor-Propagating Potential of Glioblastoma Stem-like Cells
(Elsevier BV, 2014) Suva, Mario; Rheinbay, Esther; Gillespie, Shawn M.; Patel, Anoop Premswaroop; Wakimoto, Hiroaki; Rabkin, Samuel; Riggi, Nicolo; Chi, Anthony Wei Shine; Cahill, Daniel; Nahed, Brian; Curry, William; Martuza, Robert; Rivera, Miguel; Rossetti, Nikki; Kasif, Simon; Beik, Samantha Petrillo; Kadri, Sabah; Tirosh, Itay; Wortman, Ivo; Shalek, Alex K.; Rozenblatt-Rosen, Orit; Regev, Aviv; Louis, David; Bernstein, BradleyDevelopmental fate decisions are dictated by master transcription factors (TFs) that interact with cis-regulatory elements to direct transcriptional programs. Certain malignant tumors may also depend on cellular hierarchies reminiscent of normal development but superimposed on underlying genetic aberrations. In glioblastoma (GBM), a subset of stem-like tumor-propagating cells (TPCs) appears to drive tumor progression and underlie therapeutic resistance, yet remain poorly understood. Here, we identify a core set of neurodevelopmental TFs (POU3F2, SOX2, SALL2, OLIG2) essential for GBM propagation. These TFs coordinately bind and activate TPC-specific regulatory elements, and are sufficient to fully reprogram differentiated GBM cells to ‘induced’ TPCs, recapitulating the epigenetic landscape and phenotype of native TPCs. We reconstruct a network model that highlights critical interactions and identifies novel therapeutic targets for eliminating TPCs. Our study establishes the epigenetic basis of a developmental hierarchy in GBM, provides detailed insight into underlying gene regulatory programs, and suggests attendant therapeutic strategies.
Publication Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma
(American Association for the Advancement of Science (AAAS), 2014) Patel, Anoop Premswaroop; Tirosh, I.; Trombetta, J. J.; Shalek, Alexander; Gillespie, S. M.; Wakimoto, Hiroaki; Cahill, Daniel; Nahed, Brian; Curry, William; Martuza, Robert; Louis, David; Rozenblatt-Rosen, O.; Suva, Mario; Regev, A.; Bernstein, BradleyHuman cancers are complex ecosystems composed of cells with distinct phenotypes, genotypes and epigenetic states, but current models do not adequately reflect tumor composition in patients. We used single cell RNA-seq to profile 430 cells from five primary glioblastomas, which we found to be inherently variable in their expression of diverse transcriptional programs related to oncogenic signaling, proliferation, complement/immune response and hypoxia. We also observed a continuum of stemness-related expression states that enabled us to identify putative regulators of stemness in vivo. Finally, we show that established glioblastoma subtype classifiers are variably expressed across individual cells within a tumor and demonstrate the potential prognostic implications of such intratumoral heterogeneity. Thus, we reveal previously unappreciated heterogeneity in diverse regulatory programs central to glioblastoma biology, prognosis, and therapy.