Scott W. Canna, M.D.

  • Assistant Professor of Pediatrics and Immunology
  • Scholar, Mellon Institute for Pediatric Research

Major Lectureships

  • “IL-18 at the Intersection of Auto- and Hyperinflammation,” invited presentation, KFO 249 Symposium: Defects of the innate immune system in autoinflammation and autoimmunity, Dresden, Germany, August 2017
  • “IL-18 at the Intersection of Auto- and Hyperinflammation,” invited presentation , FOCIS Annual Meeting, NIH Immunology Interest Group Symposium, Chicago, Ill., June 2017
  • “Chronic IL-18 of Diverse Origins Defines and Drives the Hyperinflammatory Macrophage Activation Syndrome,” oral abstract presentation, Keystone Pattern Recognition Signaling Symposium, Banff, Alberta, Canada, March 2017
  • “CNS manifestations of Autoinflammatory Disease,” CHP Neuroimmunology conference, March 2017
  • “Cytokines in Systemic Inflammation: following the monogenic breadcrumb path,” Children’s Hospital of Pittsburgh Molecular Medicine Research Seminar, Pittsburgh, Pa., January 2017
  • “IL-18 at the Intersection of Auto- and Hyper-Inflammation,” University of Pittsburgh Department of Immunology Seminar Series, Pittsburgh, Pa., 12/15/16

Professional Affiliations/Society Memberships

  • 2006-present  American Academy of Pediatrics
  • 2009-present  American College of Rheumatology
  • 2010-present  Childhood Arthritis and Rheumatology Research Alliance (CARRA)
  • 2013-present  Histiocyte Society

Regulatory Experience Human

  • 2017-present  Associate Investigator and Site PI, Therapeutic Use of Tadekinig Alfa in NLRC4 Mutation and XIAP Deficiency, NCT03113760
  • 2017-present  Principal Investigator, University of Pittsburgh Human Subjects Protocol PRO16120025, Natural History of Autoinflammatory Disease
  • 2016-present  Associate Investigator, NIAID protocol 17-I-0016, Natural History, Pathogenesis, and Outcome of Autoinflammatory Diseases (NOMID/CAPS, DIRA, CANDLE, SAVI, NLRC4-MAS, Still’s-like Diseases, and Other Undifferentiated Autoinflammatory Diseases), NCT02974595.
  • 2013-present  Sub-Investigator, Childhood Arthritis & Rheumatology Research Alliance Legacy Registry

Regulatory Experience Animal

  • 2016-present  Principal Investigator, Animal Protocol 16129653.

Study Sections

  • Childhood Arthritis & Rheumatology Research Alliance (CARRA) Scientific Review Committee, 2017-present
  • Peer Reviewer, Rheumatology Research Foundation Innovative Research Award, Basic Science Section, 2016-present
  • Abstract Reviewer, American College of Rheumatology Annual Scientific Meeting, 2016-present

Advisory Committee Memberships

  • Medical Advisory Board, AB2Bio Ltd., Geneva, Switzerland, 2015 to the present

Editorships

  • Arthritis and Rheumatology
  • Frontiers in Immunology

Education & Training

  • MD: George Washington University School of Medicine - 2006
  • Residency: Pediatrics, University of Colorado - 2009
  • Fellowship: Pediatric Rheumatology, Children’s Hospital of Philadelphia - 2012

Representative Publications

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.

Research Interests

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, specifically, two related disorders that typify the concept of hyperinflammatory SIRS, Hemophagocytic Lymphohistiocytosis (HLH) and Macrophage Activation Syndrome (MAS). 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

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