Scott Canna, MD
Campus: 3615 Civic Center Blvd
Office: 1110A ARC
Philadelphia, PA 19104
- Fellowship, Pediatric Rheumatology, Children’s Hospital of Philadelphia, 2012
- Residency, Pediatrics, University of Colorado, 2009
- MD, George Washington University School of Medicine, 2006
- BA, Johns Hopkins University, 2001
- Assistant Professor (Adjunct), Department of Pediatrics
- Assistant Professor (Adjunct), Secondary, Department of Immunology
Inflammation is a core pathogenic mechanism in virtually every disease process. Systemically, this culminates in the Systemic Inflammatory Response Syndrome (SIRS), identified since ancient times as sepsis. Blocking inflammation in SIRS has been largely disappointing, conferring neither broad benefit nor harm. We use genetic and functional insights from patients and model systems to find ways to subtype SIRS/sepsis patients in diagnostically and therapeutically meaningful ways.
Patients found to have monogenic defects causing excessive innate immune responses have been particularly helpful. Most “autoinflammatory” patients have chronic organ-specific or systemic inflammation, but not typically SIRS. The dramatic response of many “autoinflammatory” patients to inhibition of the inflammasome-activated cytokine IL-1 has reinvigorated the quest for anti-inflammatory targets in SIRS and reinforced the therapeutic potential of targeting the inflammasome and related innate immune pathways.
Our group studies the intersections of hyper- and auto-inflammation. In particular, we study two related disorders, Hemophagocytic Lymphohistiocytosis (HLH) and Macrophage Activation Syndrome (MAS), becauase they typify the concept of hyperinflammatory SIRS. Whereas the pathogenesis of HLH clearly includes the inflammatory effects of defects in granule-mediated cytotoxicity, the mechanisms at work in MAS are less clear. We combine clinical insights from rheumatology and innate immunity with basic models of overwhelming systemic inflammation to define new disease subtypes and disease activity biomarkers, to flesh out mechanisms of inflammatory disease, and to test promising therapeutic strategies.
- Determining the pertinent differences in inflammasome localization activation that distinguish clinical inflammasomopathies.
- Identifying the relevant triggers for and sources of pathogenic cytokines in human autoinflammatory diseases.
- Understanding the effects of IL-1 family cytokines, particularly IL-18, in driving Macrophage Activation Syndrome and other autoinflammatory diseases.
- Identifying new autoinflammatory biomarkers, diseases, and pathogenic mechanisms.
Canna SW, Girard C, Malle L, de Jesus A, Romberg N, Kelsen J, et al. Life-threatening NLRC4-associated hyperinflammation successfully treated with Interleukin-18 inhibition. The Journal of allergy and clinical immunology. 2016.
de Jesus AA*, Canna SW*, Liu Y*, Goldbach-Mansky R. Molecular mechanisms in genetically defined autoinflammatory diseases: disorders of amplified danger signaling. Annu Rev Immunol. 2015;33:823-74. *Equal Contribution
Canna SW, de Jesus AA, Gouni S, Brooks SR, Marrero B, Liu Y, et al. An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome. Nat Genet. 2014;46(10):1140-6.
Canna SW, Wrobel J, Chu N, Kreiger PA, Paessler M, Behrens EM. Interferon-gamma mediates anemia but is dispensable for fulminant toll-like receptor 9-induced macrophage activation syndrome and hemophagocytosis in mice. Arthritis Rheum. 2013;65(7):1764-75.
Behrens EM, Canna SW, Slade K, Rao S, Kreiger PA, Paessler M, et al. Repeated TLR9 stimulation results in macrophage activation syndrome-like disease in mice. J Clin Invest. 2011;121(6):2264-77.
Goldbach-Mansky R, Dailey NJ, Canna SW, Gelabert A, Jones J, Rubin BI, et al. Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition. The New England journal of medicine. 2006;355(6):581-92.