In an innate immune response, cells recognize foreign antigens and begin to produce proteins that aid in the development of immunity. TLR receptor proteins bind the foreign antigens and activate a cascade that induces expression of immune response genes. One gene that is activated by the TLR pathway in mouse cells is fus, the human homolog of which is TLS (translocated in liposarcoma).
Jake and his mentors sought to determine the function and downstream targets of the fus protein. Jake stimulated mouse cells with different TLR ligands, and used RNAi to knock down fus gene expression. He then used Affymetrix microarrays to measure the effects of knocking down fus activity. He found that fus regulates tissue growth and cancer-related genes, and that the absence of functional fus leads to the upregulation of known oncoproteins. Jake hypothesizes that fus acts as a tumor suppressor protein by repressing oncogene expression.