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Barbie, David

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Barbie

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Barbie, David

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2013 - 20164

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Author's Publications: search.filters.isAuthorOfPublication.b32ef6c3-febe-4ff6-afea-1feb463c21bd

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Now showing 1 - 4 of 4
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    Whole-exome sequencing and clinical interpretation of FFPE tumor samples to guide precision cancer medicine
    (2013) Allen, Eliezer M. Van; Wagle, Nikhil; Stojanov, Petar; Perrin, Danielle L.; Cibulskis, Kristian; Marlow, Sara; Jane-Valbuena, Judit; Friedrich, Dennis C.; Kryukov, Gregory; Carter, Scott L.; McKenna, Aaron; Sivachenko, Andrey; Rosenberg, Mara; Kiezun, Adam; Voet, Douglas; Lawrence, Michael; Lichtenstein, Lee T.; Gentry, Jeff G.; Huang, Franklin; Fostel, Jennifer; Farlow, Deborah; Barbie, David; Gandhi, Leena; Lander, Eric; Gray, Stacy; Joffe, Steven; Janne, Pasi; Garber, Judy; MacConaill, Laura; Lindeman, Neal; Rollins, Barrett; Kantoff, Philip; Fisher, Sheila A.; Gabriel, Stacey; Getz, Gad; Garraway, Levi
    Translating whole exome sequencing (WES) for prospective clinical use may impact the care of cancer patients; however, multiple innovations are necessary for clinical implementation. These include: (1) rapid and robust WES from formalin-fixed paraffin embedded (FFPE) tumor tissue, (2) analytical output similar to data from frozen samples, and (3) clinical interpretation of WES data for prospective use. Here, we describe a prospective clinical WES platform for archival FFPE tumor samples. The platform employs computational methods for effective clinical analysis and interpretation of WES data. When applied retrospectively to 511 exomes, the interpretative framework revealed a “long tail” of somatic alterations in clinically important genes. Prospective application of this approach identified clinically relevant alterations in 15/16 patients. In one patient, previously undetected findings guided clinical trial enrollment leading to an objective clinical response. Overall, this methodology may inform the widespread implementation of precision cancer medicine.
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    Doxycycline: new tricks for an old drug
    (Impact Journals LLC, 2015) Barbie, David; Kennedy, Brian K.
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    Fine needle aspirate flow cytometric phenotyping characterizes immunosuppressive nature of the mesothelioma microenvironment
    (Nature Publishing Group, 2016) Lizotte, Patrick H.; Jones, Robert E.; Keogh, Lauren; Ivanova, Elena; Liu, Hongye; Awad, Mark; Hammerman, Peter S.; Gill, Ritu; Richards, William; Barbie, David; Bass, Adam; Bueno, Raphael; English, Jessie M.; Bittinger, Mark; Wong, Kwok-Kin
    With the emergence of checkpoint blockade and other immunotherapeutic drugs, and the growing adoption of smaller, more flexible adaptive clinical trial designs, there is an unmet need to develop diagnostics that can rapidly immunophenotype patient tumors. The ability to longitudinally profile the tumor immune infiltrate in response to immunotherapy also presents a window of opportunity to illuminate mechanisms of resistance. We have developed a fine needle aspirate biopsy (FNA) platform to perform immune profiling on thoracic malignancies. Matching peripheral blood, bulk resected tumor, and FNA were analyzed from 13 mesothelioma patients. FNA samples yielded greater numbers of viable cells when compared to core needle biopsies. Cell numbers were adequate to perform flow cytometric analyses on T cell lineage, T cell activation and inhibitory receptor expression, and myeloid immunosuppressive checkpoint markers. FNA samples were representative of the tumor as a whole as assessed by head-to-head comparison to single cell suspensions of dissociated whole tumor. Parallel analysis of matched patient blood enabled us to establish quality assurance criteria to determine the accuracy of FNA procedures to sample tumor tissue. FNA biopsies provide a diagnostic to rapidly phenotype the tumor immune microenvironment that may be of great relevance to clinical trials.
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    Long-term Benefit of PD-L1 Blockade in Lung Cancer Associated with JAK3 Activation
    (American Association for Cancer Research (AACR), 2015) Van Allen, Eliezer; Golay, H. G.; Liu, Yan; Koyama, S.; Wong, Kwok-Kin; Taylor-Weiner, Amaro; Giannakis, Marios; Harden, M.; Rojas-Rudilla, V.; Chevalier, A.; Thai, T.; Lydon, C.; Mach, S.; Wong, J. A.; Rabin, A. R.; Helmkamp, J.; Sholl, Lynette; Carter, Scott; Oxnard, Geoffrey; Janne, Pasi; Getz, Gad; Lindeman, Neal; Hammerman, Peter S.; Garraway, Levi; Hodi, Frank; Rodig, Scott; Dranoff, Glenn; Barbie, David
    PD-1 immune checkpoint blockade occasionally results in durable clinical responses in advanced metastatic cancers. However, mechanism-based predictors of response to this immunotherapy remain incompletely characterized. We performed comprehensive genomic profiling on a tumor and germline sample from a patient with refractory lung adenocarcinoma who achieved marked long-term clinical benefit from anti-PD-L1 therapy. We discovered activating somatic and germline amino acid variants in JAK3 that promoted PD-L1 induction in lung cancer cells and in the tumor immune microenvironment. These findings suggest that genomic alterations that deregulate cytokine receptor signal transduction could contribute to PD-L1 activation and engagement of the PD-1 immune checkpoint in lung cancer.