Description:

The Department of Biochemistry and Molecular Genetics welcomes faculty candidate:

Sachet Ashok Shukla, PhD
Senior Scientist, Medical Oncology
Dana-Farber Cancer Institute, Boston, MA

Neoantigens comprise a class of tumor-specific antigens derived from somatic lesions in the tumor, and may provide highly specific targets for therapeutic intervention. Class I HLA genes constitute the most polymorphic locus in the human genome and are critical for recognition of neoantigens by the immune system. In this talk I will describe Polysolver (POLYmorphic loci reSOLVER), a computational tool that enables accurate inference of germline alleles of class I HLA-A, B and C genes, as well as a neoantigen prediction pipeline for the rational design of neoantigen-based vaccines. These methods have led to identification of immunological correlates of several biological and clinical features in multiple tumor types, and have been deployed in two first-in-man neoantigen-based vaccine trials. Furthermore, a pan-cancer analysis of HLA mutations using a Polysolver-based pipeline supports the notion of immune evasion by altered HLA function as a contributory mechanism in cancer. These immunogenomic strategies can thus be harnessed both for elucidating underlying principles of tumor immune interactions as well as for therapeutic applications in the clinic.