Research Focus

Antigen-specific T lymphocytes are critical orchestrators and effectors of nearly all adaptive immune responses. Although they are key determinants for a wide range of disease outcomes, study of these cells is difficult because the identities of peptide antigens they will target are unpredictable and because cells specific for any given antigen can be extremely rare in the blood. However, once these cells are identified, their frequency, phenotypes and functional capabilities are highly indicative of the status of the corresponding immune response.

The focus of the laboratory is to apply and develop new methods that take advantage of single-cell mass spectrometry (a.k.a., mass cytometry or Cytometry by Time-Of-Flight, CyTOF) for the identification and characterization of antigen specific T cells. This information will then be used to identify novel correlates of clinical outcomes for a variety of diseases.

The CyTOF, up and running at SIgN, is a next-generation flow cytometer based on Inductively Coupled Plasma – Mass Spectrometry (ICP-MS) that uses heavy metal isotopic tags to tag antibodies (or peptide-MHC tetramers in this case) instead of fluorophores. The benefits of using isotopic tagging instead of fluorescent tagging is that there is very little crosstalk between channels and there are many more channels available (now we are acquiring >40 independent parameters per cell). The lab will be using novel multiplexing technology (see Newell et al., Nature Methods 2009) together with this system to probe large number of T cell antigen specificities in the same sample. Then, with a large number of remaining channels we can probe the phenotypic and functional characteristics of these cells in depth (see Newell et al., Immunity 2012).

Biography

Evan Newell completed his B.Sc. in Immunology at McGill University and Ph.D. in Physiology focusing on the electrophysiological properties of immune cells under the guidance of Dr. Lyanne Schlichter at the University of Toronto. He then moved to California for a post-doctoral fellowship at Stanford University with Dr. Mark Davis, where he initiated the use of mass cytometry for the study of antigen-specific cells using heavy-metal labeled peptide-MHC tetramers. Evan joined SIgN July 2012.