John Altin Ph.D.

John Altin is an Assistant Professor who works jointly across the Pathogen Genomics and Integrated Cancer Genomics Divisions. His research interests lie at the intersection of T cell immunology and genomics, where he studies the human T cell response in the context of both pathogens and tumors, two settings where an ability to reliably invoke a successful immune response holds great promise for public health.

John began his research career in the Immunogenomics lab of Chris Goodnow, where he used genome-wide mouse mutagenesis and cellular immunology techniques to reveal new pathways of T cell regulation (Altin et al 2011, Altin et al 2012, Altin et al 2014). After graduating in 2012, he joined Prognosys Biosciences, a start-up biotech company founded by Mark Chee in San Diego that develops novel, highly parallel tools for proteomics. John applied this technology to the adaptive immune system, developing new assays to view T and B lymphocyte responses at high-resolution (US2016-0291007-A1, US2016-0025726-A1). Building on this training in cellular immunology and highly multiplexed genomic assay development, John is now working to generate a systems-level understanding of human T cell immunity, which he hopes can lay the groundwork for new approaches to the diagnosis and treatment of cancers and pathogen-mediated disease.

T cell immunity can be viewed as the outcome of a clash between the host genome and an immunogen genome (where the latter could be a tumor or pathogen). This clash comes into sharp focus at the tri-molecular interface of peptide MHC-TCR, which forms the molecular trigger for a highly specific and long-lasting immune response. MHC and TCR are host-encoded – MHC by a set of genomic loci that are highly polymorphic across individuals, and TCR by a series of somatic events that generate diversity within each host. The peptide sequence, on the other hand, is derived from the immunogen’s genome. The interaction of these three diversely sourced proteins gives rise to an astronomical molecular diversity. At the same time, subtle variations in sequence can underlie large differences in pathological outcome, exemplified by associations between HLA genotype and various disease states, and also by the ability of a single amino acid variant to trigger a protective anti-tumor response. Diversity in the T cell response also arises in another dimension: responding T cells can occupy diverse differentiation states, each underpinning a different type of immune activity.

Projects in the lab will apply genomics tools (both wet-lab and informatic) and cellular immunology techniques to view and understand these layers of diversity in the human T cell response at a systems level. Current research projects will be described in more detail on the lab website.