Research

The Costello laboratory is composed of molecular and computational biologists working alongside clinician-scientists. Our goal is to understand the full life history of human tumors, from the first mutation and epimutation through clonal selection and tumor recurrence. 

We use next-generation sequencing to discover patterns and interdependencies of genetic mutations, epigenetic alterations and gene expression changes. Current projects incorporate MRI guided tumor biopsies and treatment data with longitudinal genomics to allow the reconstruction of tumor evolution in the context of the human tumor in vivo.  In collaboration with the Okada laboratory, we will be exploring the application of immune therapies to target tumor specific mutations in tumors that emerge as hypermutated following chemotherapy. 

On the gene level, we recently discovered the mechanism by which mutations in the TERT gene promoter leads to telomerase activation and are pursuing further mechanistic and therapeutic studies aimed at reversing tumor cell immortality. TERT promoter mutation is one of the most common mutations in cancer in adults and may represent a viable cancer-specific target for future therapeutics.