• Brown, Kelly

    Titles

    Investigator, BC Children's Hospital
    Assistant Professor, Division of Rheumatology, Department of Pediatrics, University of British Columbia

    Degrees / Designations

    PhD

    Primary Area of Research
    Childhood Diseases
    Secondary Area(s) of Research
    Phone
    604 875 2000 ext. 7984
    Fax
    Lab Phone
    604 875 2000 ext. 7625
    Mailing Address

    BC Children's Hospital Research Institute
    Room A5-141
    950 West 28th Avenue
    Vancouver, BC V5Z 4H4

    Affiliate Websites
    Research Areas
    • Autoinflammation
    • Primary Childhood Vasculitis
    • Neonatal Hypoxic Ischemic Encephalopathy
    • Rheumatic Disease
    • Phagocyte Biology
    • Systems Biology
    • Cellular Redox State
    • Anti-inflammatory Agents
    • Subclinical Biomarkers
    • Knowledge Translation 
    Summary

    In Canada, rheumatic conditions are the most common chronic illness of childhood, affecting as many as 10 000 of our children and youth. Examples of rheumatic diseases are juvenile idiopathic arthritis, lupus, vasculitis and autoinflammatory conditions. The common denominator for all is pain and / or inflammation in joints, muscles, and critical organs. Some diseases are life- or organ- threatening and all have significant potential for lifelong poor health and disability. There are no cures and remarkably few treatments that are specific and safe for a growing child. My research program is designed to generate an evidence base for clinical decisions that ultimately improve outcomes for Canadian children and families affected by rheumatic disease.

    Current Projects

    Primary Childhood Vasculitis
    Chronic primary vasculitis describes a group of rare, life-threatening diseases that have in common inflammation of blood vessels in vital organs such as kidneys, lungs and brain. The challenge in treating children with vasculitis is balancing the risk of under treating aggressive disease with the potential damaging side-effects of prolonged use of drugs. This project uses an established international web-based registry to collect clinical information from 50 or more centers worldwide, with approximately 20 centres contributing paired biological samples (DNA, RNA, plasma, serum, urine). The goal is to elucidate subclinical (molecular/cellular) features which help to classify, define and direct optimal treatment for children with vasculitis.

    Childhood Autoinflammatory Diseases
    The autoinflammatory family of diseases share features of unprovoked, recurrent attacks of inflammation with fever, rash, body pain/arthritis, and organ inflammation. The family includes a handful of defined monogenic diseases, but more than 80% of cases do not have a known cause. This collaborative project will establish a clinical home at BCCH for children with autoinflammatory disorders, and develop in parallel a robust, longitudinal collection of clinical data and biological samples for research. Laboratory initiatives will evaluate the clinical potential of previously identified, putative biomarkers of autoinflammation, and seek to uncover new disease etiologies.

    Inflammation and Cellular Redox States
    It is well understood that highly toxic oxidants called ‘reactive oxygen species (ROS)’ are produced by phagocytic cells as part of the innate immune response to infection. In recent years, ROS and consequently the oxidation-reduction (redox) state of immune cells have been recognized as key players in the inflammatory response to both infectious and non-infectious cues. Pediatric diseases with inflammatory complications and signs of redox imbalance include chronic granulomatous disease (CGD), cystic fibrosis, and the autoinflammatory diseases SAPHO, PFAPA, TRAPS and FMF. Whether oxidants suppress or promote inflammatory signaling and to what extent they influence the biology of an inflammatory response remains controversial. This project aims to understand redoxsensitive signaling molecules in the context of inflammatory disease and their potential as novel therapeutic targets.

    Neonatal Hypoxic-Ischemic Brain Inflammation and Injury
    Hypoxic-ischemic (HI) induced injury in infants can result from maternal infection or oxygen deprivation during birth and is an important contributor to neonatal mortality or permanent neurological impairment. The inflammatory response to HI is as important of a contributor to injury severity as is the initial period of oxygen deprivation. This collaborative project explores the mechanistic action of a novel immunomodulatory and neuroprotective peptide and aims to identify key inflammatory regulators that correlate with improved outcomes.

    Selected Publications

    REW, Brown KL*, Mallard C* (2014) Innate defence regulatory peptide protects against neonatal brain injury. Annals of Neurology 75:395-410. *authors contributed equally. PMID: 24339166.

    Sundqvist M, Wekell P, Osla V, Bylund J, Christenson K, Sävman K, Fasth A, Berg S, Brown KL*, Karlsson A* (2013) Increased intracellular oxygen radical production in neutrophils during febrile episodes of PFAPA syndrome. Arthritis & Rheumatism 65:2971-2983. *authors contributed equally. PMID: 23983059.

    Brown KL*, Poon GF*, Birkenhead D, Pena OM, Falsafi R, Dahlgren C, Karlsson A, Bylund J, Hancock REW and Johnson P (2011) Host defence peptide LL-37 selectively reduces proinflammatory macrophages responses. J. Immunol. 186:5497-5505. PMID 21441450. *authors contributed equally. PMID: 21441450.

    Brown KL, Wekell P, Karlsson A, Berg S (2011) On the road to discovery in periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome. Proc. Natl. Acad. Sci. U.S.A 108:E525. PMID: 21810991.

    Forsman H, Islander U, Andréasson E, Andersson A, Önnheim K, Karlström A, Sävman K, Magnusson M, Brown KL and Karlsson A (2011) Galectin-3 aggravates joint inflammation and destruction in antigen-induced arthritis. Arthritis & Rheumatism 63:445-454. Sävman K and Brown KL (2010) Treating Neonatal Brain Injury - Promise and Inherent Research Challenges. Recent Pat Inflamm Allergy Drug Discov 4(1):16-24. PMID: 21280000.

    Bylund J, Brown KL, Movitz C, Dahlgren C and Karlsson A (2010) Intracellular Generation of Superoxide by the Phagocyte NADPH-Oxidase; How, Where, and What for? Free Radic Biol Med. 49:1834-1845. PMID: 20870019.

    Brown KL, Falsafi R, Kum W, Hamill P, Gardy JL, Davidson DJ, Finlay BB, Turvey SE, Speert DP and Hancock REW (2010) Robust TLR4-induced gene expression patterns are not an accurate indicator of human immunity. J. Transl. Med. 8:6-17. PMID: 20105294.

    Brown KL*, Wekell P*, Osla V, Sundqvist M, Sävman K, Fasth A, Karlsson A, Berg S (2010) Profile of blood cells and inflammatory mediators in periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome. BMC Pediatrics 10:65. PMID: 20819226.

    Brown KL (2010) Anti-inflammatory/ Analgesics: an in-depth look at p38 MAP kinases. In: Development of Therapeutic Agents Handbook (Pharmaceutical Development series). pp. 673-706 (SC Gad, ed) John Wiley & Sons Ltd.

    Grants

    (Gibson), 07/2014 - 06/2014, “Exome sequencing of an undefined autoinflammatory disease is a family affair”

    Novartis Education Grant (co-PIs K. Brown and L Tucker), 01/2015 - 12/2016, “Pediatric Autoinflammatory Research Consortium (PARC)”

    European Commission 7th Framework Programme (co-PIs K Brown and J Bylund), 04/2008 - 03/2011, “Characterization of reactive oxygen species as innate immune system mediators that control inflammation”

    Swedish Research Council (PI M. Olsson, co-PIs P Johnson, L Tucker, K Brown, H Erlandsson-Harris), 07/2014 - 06/2017, “Unprovoked Inflammation: A translational study of the underlying causes of rheumatic and autoinflammatory diseases of childhood”

    Honours & Awards

    2013 Translational Medicine Certification Bursary, Dutch Arthritis Foundation

    2010 60th Nobel Laureate Meeting attendee (international competition)

    2009 Marie Curie Postdoctoral Fellowship, European Commission 7th Framework Programme

    2008 Postdoctoral Fellowship, King Gustaf V’s 80 year fund, Sweden

    2007 Postdoctoral Fellowship, Wenner-Gren Foundation, Sweden

    2005 Postdoctoral Fellowship, CIHR-UBC Strategic Program for Translational Research

    2002 Doctoral Trainee Fellowship, Michael Smith Foundation for Health Research

    1999 Doctoral Research Fellowship, Heart and Stroke Foundation of Canada

    1991 Jane Norman Memorial Student-Athlete Bursary, Simon Fraser University

    1991 Alexander Rutherford Heritage Scholarship, Provincial Government of Alberta

    Research Group Members