*Unable to make it to Scaife Hall? Dr. Canna’s lecture will be available via live stream to people with Pitt login credentials by clicking this link (sign in using your Pitt username and password): https://pitt.hosted.panopto.com/Panopto/Pages/Viewer.aspx?id=6f608b73-7f44-4639-b29f-a8e2013c2179. If you have problems with the video, contact the CSSD help line at 412-624-4357 (4-HELP).

Topic Overview:
Despite decades of intensive study, researchers are still ignorant about how to quell the inflammatory response driving organ damage and death in sepsis. As a result, sepsis remains a leading cause of morbidity and death even in the United States. After 20 years of translating disappointments in sepsis immunotherapy into groundbreaking treatments for arthritis and autoinflammation, rheumatologists are poised to return the favor.

To that end, the Canna lab leverages insights from rheumatic and genetic diseases of excessive inflammation to help identify patterns—and, more importantly, novel treatments—in life-threatening systemic inflammation. To accomplish this, Canna and colleagues combine careful characterization and comparison of monogenic diseases, broad-based biomarker discovery, and hypothesis-testing in systems designed to model findings.

For example, Canna and colleagues recently identified a genetic link between a sepsis-like state called Macrophage Activation Syndrome, an intracellular complex called the NLRC4 inflammasome, and a cytokine called Interleukin-18. This discovery has identified a new risk factor for systemic hyperinflammation with implications for the cross-talk between mucosal and systemic inflammation. Most importantly, it has augmented their ability to rationally identify and potentially treat a subset of patients with hyperinflammatory sepsis.

Given the major role of inflammation in nearly every disease process, Canna and colleagues believe that their work will help guide rationally targeted immunotherapy as the mainstay of 21st century precision medicine.