Kira Cozzolino

Roles of CDK19 in the interferon response in Down syndrome

Down syndrome is caused by triplication of chromosome 21, resulting in a range of symptoms that includes chronic hyperactivation of the inflammatory response, which is driven at the cellular level by interferon signaling. It was recently discovered by the Taatjes lab, working with the Kovarik lab (MPL, Vienna), that the Mediator kinases (CDK8 and its paralog CDK19) are key regulators of the interferon response. While CDK8, the better characterized of these kinases, activates the interferon response through phosphorylation of protein substrates, the enzymatic activity of CDK19 is dispensable, suggesting that it instead serves as a molecular scaffold. My project focuses on characterizing how CDK19 might regulate the interferon response in Down syndrome, using patient-derived cell lines in which CDK19 can be rapidly depleted or rapidly inhibited. Through systems-level approaches, I hope to elucidate whether CDK19 might be a therapeutic target for Down syndrome and other conditions involving dysregulation of inflammatory responses.