Some of Stark’s most important advancements have been within the realm of interferon-dependent signalling. These studies began at Stanford and continued during his time in London, where his lab focused on these pathways, along with mechanisms of gene amplification, and this research has continued throughout the rest of his career. Stark’s lab group, in collaboration with Ian M. Kerr’s group at the Imperial Cancer Research Fund, was attempting to identify the key components of IFN-dependent signaling. Interferons induce antiviral activities, inhibit cell growth, control apoptosis, and are implicated in promoting immune responses. Concurrently with James E. Darnell’s lab group, Stark’s group was able to uncover a new direct signal transduction pathway through their study of interferon alpha and interferon gamma. This particular pathway, better known as the JAK-STAT signaling pathway, is characterized by the interaction of interferon receptors at the cell’s surface with Janus kinases (JAKs), which are then able to phosphorylate substrate proteins called signal transducers and activators of transcription (STATs). These STAT proteins then migrate to the nucleus and then initiate transcription.  These proteins are also involved in the resistance of cancer cells to DNA damaging therapies, and this is just one of the many topics that Stark has focused on during his research career at the Case Comprehensive Cancer Center.
