Scott Canna, MD
8124 Rangos Research Bldg
Pittsburgh, PA 15224
- MD, George Washington University, Washington, D.C.
- BA, Johns Hopkins University, Baltimore, Md.
Scholar, RK Mellon Institute for Pediatric Research, Children’s Hospital of Pittsburgh of UPMC
Assistant Professor of Pediatrics and of Immunology, University of Pittsburgh
Pediatric Rheumatologist, Children’s Hospital of Pittsburgh of UPMC
Special Volunteer, Translational Autoinflammatory Disease Studies Unit, NIAID/NIH
Inflammation is a core pathogenic mechanism in virtually every disease process. Systemically, this culminates in the Systemic Inflammatory Response Syndrome (SIRS, a.ka. sepsis when triggered by infection). At the far extremes of SIRS are the hyperinflammatory “Cytokine Storm Syndromes” (although their pathogenesis involves more than just cytokines). Given the complexity of systemic inflammation, our lab specifically leverages insights from patients found to have single-gene defects causing excessive innate immune responses. Such “autoinflammatory” patients usually have organ-specific or systemic inflammation, but only a few gene defects cause systemic hyperinflammation.
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). Whereas the pathogenesis of HLH clearly includes the inflammatory effects of impaired 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.
1. Comparing the differential effects of intrinsic inflammasome hyperactivity
2. Identifying the relevant triggers for and sources of pathogenic cytokines in human autoinflammatory diseases
3. Understanding the effects of mucosal and systemic IL-18 in MAS and other autoinflammatory diseases
4. Assessing the importance of non-classical MHC-II antigen presentation
Weiss ES, Girard-Guyonvarc’h C, Holzinger D, de Jesus AA, Tariq Z, Picarsic J, Schiffrin EJ, Foell D, Grom AA, Ammann S, Ehl S, Hoshino T, Goldbach-Mansky R, Gabay C and Canna SW. 2018. Dysregulation of Interleukin-18 Diagnostically Distinguishes and Pathogenically Promotes human and murine Macrophage Activation Syndrome. Blood. 131: 1442-1455.
Canna SW, Girard C, Malle L, de Jesus AA, Romberg N, Kelsen J, Surrey LF, Russo P, Sleight A, Schiffrin E, Gabay C, Goldbach-Mansky R, Behrens EM. 2016. Life-threatening NLRC4-associated hyperinflammation successfully treated with Interleukin-18 inhibition. J Allergy Clin Immunol. 6749: 31352-31355.
Canna SW, de Jesus AA, Gouni S, et al. 2014. An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome. Nat Genet. 46: 1140-1146.
Schulert GS and Canna SW. 2018. Convergent Pathways of the Hyperferritinemic Syndromes. International Immunology. Epub ahead of pring.
Goldbach-Mansky R, Dailey NJ, Canna SW, et al. 2006. Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition. The New England journal of medicine. 355: 581-592.