JAN 27, 2017 4:00 AM PST

WEBINAR: Highly Multiplexed Single Cell Analysis Of Tumor Heterogeneity Through Time and Space by Mass Cytometry

Speakers
  • Professor for Quantitative Biology, University of Zurich
    Biography
      Bernd Bodenmiller (1979) studied biochemistry at the University of Bayreuth and ETH Zürich and obtained his PhD for his work on system-wide signaling network analysis in the laboratory of Ruedi Aebersold at ETH Zürich. For his postdoctoral training, he joined the laboratory of Garry P. Nolan at Stanford University. There he developed methods for the high throughput analysis of signaling network states by mass cytometry, a technology that allows in principle to quantify 135 proteins and signaling molecules at the single cell level. In 2012, he became group leader and in 2013 SNF/ERC assistant professor at the Institute of Molecular Life Sciences at the University of Zürich. Currently his group is developing methods for highly multiplexed imaging by mass cytometry (Giesen et al, Nature Methods, 2014) to unravel how trans-cellular signaling network interactions in the tumor microenvironment drive cancer development and ultimately might be exploited for therapeutic targeting.
    • Director, Cytometry, Cell Signaling Technology
      Biography
        Dr. Wetzel has been at Cell Signaling Technology for 15 years and currently leads the antibody testing and validation team, the antibody conjugation team, and an assay development team specializing in ELISA, bead assay, and multiplex IHC kits. His areas of expertise include: wide-field, confocal, and spectral fluorescent microscopy, automated high content imaging, flow cytometry, novel dye and conjugation chemistry, and sandwich assay (bead, ELISA, alpha) development.

      Abstract:

      DATE: January 27, 2017
      TIME: 4:00am PT, 7:00am ET, 1:00pm CET

      The study of the tumor ecosystem and its cell-to-cell communications is essential to enable an understanding of tumor biology, to define new biomarkers to improve patient care, and ultimately to identify new therapeutic routes and targets.

      To study and understand the workings of the tumor ecosystem (TME), highly multiplexed image information of tumor tissues is essential. Such multiplexed images will reveal which cell types are present in a tumor, their functional state, and which cell-cell interactions are present. To enable multiplexed tissue imaging, we developed imaging mass cytometry (IMC). IMC is a novel imaging modality that uses metal isotopes of defined mass as reporters on antibodies and currently allows the visualization of over 50 proteins simultaneously on tissues with subcellular resolution. In the near future, we expect to be able to visualize over 100 proteins. Thus highly specific, reproducible and deeply validated antibodies are essential for IMC and any multiplexed antibody based method.
       
      We applied IMC for the analysis of hundreds of breast cancer samples in a quantitative manner. Our analysis with a novel computational pipeline reveals a surprising level of inter and intra-tumor heterogeneity and identified new diversity within known human breast cancer subtypes, as well as a variety of stromal cell types that interact with them. Furthermore, we identified cell-cell interaction motifs in the tumor microenvironment correlating with clinical outcomes of the analyzed patients.
       
      In summary, our results show that IMC provides targeted, high-dimensional analysis of cell type, cell state and cell-to-cell interactions within the TME at subcellular resolution. Spatial relationships of complex cell states of cellular assemblies can be used as biomarkers. We envision that IMC will enable a systems biology approach to understand and diagnose disease and to guide treatment.

      Learning Objectives:

      • Learn about the novel imaging technique imaging mass cytometry (IMC)
      • Understand how antibody quality impacts highly multiplexed techniques

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