BCCHR Researchers Find a Researcher

Kelly Brown

PhD

Investigator, BC Children's Hospital

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.

Academic Affiliations

Associate Professor, , Department of Pediatrics, Faculty of Medicine, University of British Columbia
Research Theme: Childhood Diseases

Contact Information

Location

950 West 28th Avenue, Vancouver, British Columbia, Canada, V5Z 4H4

(604) 875-2000 ext. 7984

kbrown@bcchr.ca

Evaluating Renal Disease in Pediatric-Onset Antineutrophil Cytoplasmic Antibody"Associated Vasculitis: Disease Course, Outcomes, and Predictors of Outcome

Arthritis and Rheumatology

Toor, K.K. and Chen, A. and Cabral, D.A. and Mammen, C. and Bosman, E.S. and Shen, Y. and Bone, J.N. and Noone, D. and Al-Abadi, E. and Benseler, S. and Berard, R. and Bohm, M. and Charuvanij, S. and Cook, K. and Dancey, P. and Deepak, S. and Duffy, C. and Eberhard, B. and Elder, M. and Foell, D. and Gerstbacher, D. and Heshin-Bekenstein, M. and Huber, A. and James, K.E. and Kim, S. and Klein-Gitelman, M. and Martin, N. and McErlane, F. and Moorthy, L.N. and Myrup, C. and Riley, P. and Shenoi, S. and Sivaraman, V. and Tanner, T. and Tarvin, S. and Wagner-Weiner, L. and Yeung, R.S.M. and Brown, K.L. and Morishita, K.A.

DOI: 10.1002/art.43071

No-lyse no-wash flow cytometry method for ex vivo study of human neutrophils

Journal of Leukocyte Biology

Tsai, Y.-S. and Niemietz, I. and Sundqvist, M. and Brown, K.L.

DOI: 10.1093/jleuko/qiaf050

Comparing Rituximab and Cyclophosphamide in Induction Therapy for Childhood-Onset Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis: An ARChiVe Registry Cohort Study

Arthritis Care and Research

Gagne, S.J. and Sivaraman, V. and Bosman, E.S. and Klamer, B. and Morishita, K.A. and Huber, A. and Orjuela, A. and Eberhard, B. and Myrup, C. and Gerstbacher, D. and Foell, D. and Al-Abadi, E. and McErlane, F. and Cook, K. and Wagner-Weiner, L. and Elder, M. and Moorthy, L.N. and Dancey, P. and Yeung, R. and Khubchandani, R. and Deepak, S. and Charuvanij, S. and Tarvin, S. and Shenoi, S. and Tanner, T. and Brown, K. and Cabral, D.A.

DOI: 10.1002/acr.25455

Anti-LAMP-2 Antibody Seropositivity in Children with Primary Systemic Vasculitis Affecting Medium- and Large-Sized Vessels

International Journal of Molecular Sciences

Akbaba, T.H. and Toor, K.K. and Mann, S.K. and Gibson, K.M. and Alfaro, G.A. and Balci-Peynircioglu, B. and Cabral, D.A. and Morishita, K.A. and Brown, K.L.

DOI: 10.3390/ijms25073771

Predictive utility of ANCA positivity and antigen specificity in the assessment of kidney disease in paediatric-onset small vessel vasculitis

RMD Open

Mann, S.K. and Bone, J.N. and Bosman, E.S. and Cabral, D.A. and Morishita, K.A. and Brown, K.L.

DOI: 10.1136/rmdopen-2024-004315

Editorial: Innate immunity in vasculitis

Frontiers in Immunology

De Souza, A.W.S. and Ooi, J.D. and Misra, D.P. and Zhong, Y. and Brown, K.L.

DOI: 10.3389/fimmu.2024.1432069

Elevated ADA2 Enzyme Activity at the Onset of Chronic Graft-versus-Host Disease in Children

Transplantation and Cellular Therapy

Bowers, S.M. and Ng, B. and Abdossamadi, S. and Kariminia, A. and Cabral, D.A. and Cuvelier, G.D.E. and Schultz, K.R. and Brown, K.L.

DOI: 10.1016/j.jtct.2023.02.014

Hyaluronan promotes intracellular ROS production and apoptosis in TNFa-stimulated neutrophils

Frontiers in Immunology

Niemietz, I. and Brown, K.L.

DOI: 10.3389/fimmu.2023.1032469

Behets syndrome: recent advances to aid diagnosis

Clinical and Experimental Medicine

Akbaba, T.H. and Ekici, M. and ?olpak, A.?. and Brown, K.L. and Karada?, . and Balci-Peynircioglu, B.

DOI: 10.1007/s10238-023-01226-7

Association Between HLA"DPB1 and Antineutrophil Cytoplasmic Antibody"Associated Vasculitis in Children

Arthritis and Rheumatology

Gibson, K.M. and Drgemller, B.I. and Foell, D. and Benseler, S.M. and Graham, J. and Hancock, R.E.W. and Luqmani, R.A. and Cabral, D.A. and Brown, K.L. and Ross, C.J.

DOI: 10.1002/art.42423

Pathogenic variant c.1052T>A (p.Leu351Gln) in adenosine deaminase 2 impairs secretion and elevates type I IFN responsive gene expression

Frontiers in Immunology

Bowers, S.M. and Sundqvist, M. and Dancey, P. and Cabral, D.A. and Brown, K.L.

DOI: 10.3389/fimmu.2022.995191

Galectin-3 Modulates Microglia Inflammation in vitro but Not Neonatal Brain Injury in vivo under Inflammatory Conditions

Developmental Neuroscience

Svman, K. and Wang, W. and Rafati, A.H. and Svedin, P. and Nair, S. and Golubinskaya, V. and Ardalan, M. and Brown, K.L. and Karlsson-Bengtsson, A. and Mallard, C.

DOI: 10.1159/000517687

Latent gammaherpesvirus exacerbates arthritis and requires age-associated B cells

bioRxiv

Mouat, I.C. and Morse, Z.J. and Shanina, I. and Brown, K.L. and Horwitz, M.S.

DOI: 10.1101/2021.02.02.429395

Children with systemic autoinflammatory diseases have multiple, mixed ethnicities that reflect regional ethnic diversity

Clinical and Experimental Rheumatology

Tucker, L.B. and Niemietz, I. and Mangat, P. and Belen, M. and Tekano, J. and Cabral, D.A. and Guzman, J. and Houghton, K.M. and Morishita, K.A. and Chan, M.O. and Human, A. and Sundqvist, M. and Brown, K.L.

Different Disease Endotypes in Phenotypically Similar Vasculitides Affecting Small-to-Medium Sized Blood Vessels

Frontiers in Immunology

Gill, E.E. and Smith, M.L. and Gibson, K.M. and Morishita, K.A. and Lee, A.H.Y. and Falsafi, R. and Graham, J. and Foell, D. and Benseler, S.M. and Ross, C.J. and Luqmani, R.A. and Cabral, D.A. and Hancock, R.E.W. and Brown, K.L.

DOI: 10.3389/fimmu.2021.638571

Autoantibodies Against Lysosome Associated Membrane Protein-2 (LAMP-2) in Pediatric Chronic Primary Systemic Vasculitis

Frontiers in Immunology

Gibson, K.M. and Kain, R. and Luqmani, R.A. and Ross, C.J. and Cabral, D.A. and Brown, K.L.

DOI: 10.3389/fimmu.2020.624758

Latent gammaherpesvirus exacerbates arthritis through modification of age-associated b cells

eLife

Mouat, I.C. and Morse, Z.J. and Shanina, I. and Brown, K.L. and Horwitz, M.S.

DOI: 10.7554/eLife.67024

Adenosine deaminase 2 activity negatively correlates with age during childhood

Pediatric Rheumatology

Sarah M. Bowers and Kristen M. Gibson and David A. Cabral and Kelly L. Brown

DOI: 10.1186/s12969-020-00446-5

07 / 2020

Anti-neutrophil cytoplasmic antibodies (ANCA): Antigen interactions and downstream effects

Journal of Leukocyte Biology

Sundqvist, M. and Gibson, K.M. and Bowers, S.M. and Niemietz, I. and Brown, K.L.

DOI: 10.1002/JLB.3VMR0220-438RR

Hyaluronan primes the oxidative burst in human neutrophils

Journal of Leukocyte Biology

Niemietz, I. and Moraes, A.T. and Sundqvist, M. and Brown, K.L.

DOI: 10.1002/JLB.3MA0220-216RR

Consensus treatment plans for periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome (PFAPA): A framework to evaluate treatment responses from the childhood arthritis and rheumatology research alliance (CARRA) PFAPA work group

Pediatric Rheumatology

Amarilyo, G. and Rothman, D. and Manthiram, K. and Edwards, K.M. and Li, S.C. and Marshall, G.S. and Yildirim-Toruner, C. and Haines, K. and Ferguson, P.J. and Lionetti, G. and Cherian, J. and Zhao, Y. and Delamora, P. and Syverson, G. and Nativ, S. and Twilt, M. and Michelow, I.C. and Stepanovskiy, Y. and Thatayatikom, A. and Harel, L. and Akoghlanian, S. and Tucker, L. and Marques, M.C. and Srinivasalu, H. and Propst, E.J. and Licameli, G.R. and Dedeoglu, F. and Lapidus, S. and Laxer, R. and Imundo, L. and Tsoukas, P. and Wright, P. and Brown, K. and Khasawneh, R. and Scuccimarri, R. and Mulvihill, E. and Aabo, M. and Anderson, E. and Abramson, L. and Adelean, D. and Dumez, D. and Guzman, M. and Pang, R. and Go, E. and Koranyi, K. and Goldsmith, D. and Kim, H. and Zeft, A. and Schnieder, R. and Statler, V. and Steele, L. and Broderick, L. and Hoffman, H. and Grevich, S.C. and Chalom, E. and Cidon, M. and Sundel, R. and Saad, N. and McCurdy, D. and Schulert, G. and Yalcindag, A. and Yen, E. and Stern, S. and Durrant, K. and Butbul, Y. and Hausmann, J.

DOI: 10.1186/s12969-020-00424-x

Methods for type I interferon detection and their relevance for clinical utility and improved understanding of rheumatic diseases.

Clinical and experimental rheumatology

Lamot L and Niemietz I and Brown KL

PubMed: 30943143

03 / 2019

Monocyte-Derived Interleukin-1 As the Driver of S100A12-Induced Sterile Inflammatory Activation of Human Coronary Artery Endothelial Cells: Implications for the Pathogenesis of Kawasaki Disease

Arthritis and Rheumatology

Armaroli, G. and Verweyen, E. and Pretzer, C. and Kessel, K. and Hirono, K. and Ichida, F. and Okabe, M. and Cabral, D.A. and Foell, D. and Brown, K.L. and Kessel, C.

DOI: 10.1002/art.40784

Complexity in unclassified auto-inflammatory disease: A case report illustrating the potential for disease arising from the allelic burden of multiple variants

Pediatric Rheumatology

Tucker, L.B. and Lamot, L. and Niemietz, I. and Chung, B.K. and Cabral, D.A. and Houghton, K. and Petty, R.E. and Morishita, K.A. and Rice, G.I. and Turvey, S.E. and Gibson, W.T. and Brown, K.L.

DOI: 10.1186/s12969-019-0374-x

Comparable type i interferon score determination from PAXgene and Tempus whole blood RNA collection and isolation systems

BMC Research Notes

Lamot, L. and Niemietz, I. and Brown, K.L.

DOI: 10.1186/s13104-019-4562-z

Methods for type I interferon detection and their relevance for clinical utility and improved understanding of rheumatic diseases

Clinical and experimental rheumatology

Lamot, L. and Niemietz, I. and Brown, K.L.

Periodic fever syndromes: Beyond the single gene paradigm

Pediatric Rheumatology

Westwell-Roper, C. and Niemietz, I. and Tucker, L.B. and Brown, K.L.

DOI: 10.1186/s12969-019-0324-7

Identification of Novel Adenosine Deaminase 2 Gene Variants and Varied Clinical Phenotype in Pediatric Vasculitis

Arthritis and Rheumatology

Gibson, K.M. and Morishita, K.A. and Dancey, P. and Moorehead, P. and Drgemller, B. and Han, X. and Graham, J. and Hancock, R.E.W. and Foell, D. and Benseler, S. and Luqmani, R. and Yeung, R.S.M. and Shenoi, S. and Bohm, M. and Rosenberg, A.M. and Ross, C.J. and Cabral, D.A. and Brown, K.L.

DOI: 10.1002/art.40913

The value of creativity for enhancing translational ecologies, insights, and discoveries

Frontiers in Psychology

Goeltzenleuchter, B. and Suchtelen, A. and Brown, K.L. and Grompone, G.

DOI: 10.3389/fpsyg.2019.00951

Measles Lymphadenopathy in a Child With PFAPA Syndrome

Pediatric and Developmental Pathology

Terry, J. and Brown, K. and Hiebert, J. and Al-Rawahi, G.N. and Moxham, J.P. and Krajden, M. and Jassem, A.N. and Tucker, L.

DOI: 10.1177/1093526617727970

S100A12 Serum Levels and PMN counts are elevated in childhood systemic vasculitides especially involving proteinase 3 specific anti-neutrophil cytoplasmic antibodies

Frontiers in Pediatrics

Brown, K.L. and Lubieniecka, J.M. and Armaroli, G. and Kessel, K. and Gibson, K.M. and Graham, J. and Liu, D. and W. Hancock, R.E. and Ross, C.J. and Benseler, S.M. and Luqmani, R.A. and Cabral, D.A. and Foell, D. and Kessel, C.

DOI: 10.3389/fped.2018.00341

The importance of considering monogenic causes of autoimmunity: A somatic mutation in KRAS causing pediatric Rosai-Dorfman syndrome and systemic lupus erythematosus

Clinical Immunology

Ragotte, R.J. and Dhanrajani, A. and Pleydell-Pearce, J. and Del Bel, K.L. and Tarailo-Graovac, M. and van Karnebeek, C. and Terry, J. and Senger, C. and McKinnon, M.L. and Seear, M. and Prendiville, J.S. and Tucker, L.B. and Houghton, K. and Cabral, D.A. and Guzman, J. and Petty, R.E. and Brown, K.L. and Tekano, J. and Wu, J. and Morishita, K.A. and Turvey, S.E.

DOI: 10.1016/j.clim.2016.12.006

Elevated mitochondrial reactive oxygen species and cellular redox imbalance in human NADPH-oxidase-deficient phagocytes

Frontiers in Immunology

Sundqvist, M. and Christenson, K. and Bjrnsdottir, H. and Osla, V. and Karlsson, A. and Dahlgren, C. and Speert, D.P. and Fasth, A. and Brown, K.L. and Bylund, J.

DOI: 10.3389/fimmu.2017.01828

Clinical practice variation and need for pediatric-specific treatment guidelines among rheumatologists caring for children with ANCA-associated vasculitis: An international clinician survey

Pediatric Rheumatology

Westwell-Roper, C. and Lubieniecka, J.M. and Brown, K.L. and Morishita, K.A. and Mammen, C. and Wagner-Weiner, L. and Yen, E. and Li, S.C. and O'Neil, K.M. and Lapidus, S.K. and Brogan, P. and Cimaz, R. and Cabral, D.A.

DOI: 10.1186/s12969-017-0191-z

Endotoxin free hyaluronan and hyaluronan fragments do not stimulate TNF-a, interleukin-12 or upregulate co-stimulatory molecules in dendritic cells or macrophages

Scientific Reports

Dong, Y. and Arif, A. and Olsson, M. and Cali, V. and Hardman, B. and Dosanjh, M. and Lauer, M. and Midura, R.J. and Hascall, V.C. and Brown, K.L. and Johnson, P.

DOI: 10.1038/srep36928

Temporal characterization of microglia/macrophage phenotypes in a mouse model of neonatal hypoxic-ischemic brain injury

Frontiers in Cellular Neuroscience

Erkenstam, N.H. and Smith, P.L.P. and Fleiss, B. and Nair, S. and Svedin, P. and Wang, W. and Bostrm, M. and Gressens, P. and Hagberg, H. and Brown, K.L. and Svman, K. and Mallard, C.

DOI: 10.3389/fncel.2016.00286

Purified hyaluronan and hyaluronan fragments do not stimulate pro-inflammatory cytokine production in dendritic cells or macrophages

Scientific Reports

Dong Y, Arif AA, Olsson M, Cali V, Hardman B, Dosanjh M, Lauer M, Midura RJ, Hascall VC, Brown KL and Johnson P. (2016) Purified hyaluronan and hyaluronan fragments do not stimulate pro-inflammatory cytokine production in dendritic cells or macrophages Scientific Reports 6:36928. PMID 27869206

PubMed: 27869206

The where, when, how and why of hyaluronan binding by immune cells

Frontiers in Immunology

Lee-Sayer, S.S.M. and Dong, Y. and Arif, A.A. and Olsson, M. and Brown, K.L. and Johnson, P.

DOI: 10.3389/fimmu.2015.00150

Pediatric vasculitis: Advances in treatment

Current Opinion in Rheumatology

Morishita, K. and Brown, K. and Cabral, D.

DOI: 10.1097/BOR.0000000000000203

Innate defense regulator peptide 1018 protects against perinatal brain injury

Annals of Neurology

Bolouri, H. and Svman, K. and Wang, W. and Thomas, A. and Maurer, N. and Dullaghan, E. and Fjell, C.D. and Ek, C.J. and Hagberg, H. and Hancock, R.E.W. and Brown, K.L. and Mallard, C.

DOI: 10.1002/ana.24087

Host Defence (Antimicrobial) Peptides and Proteins

eLS

DOI: 10.1002/9780470015902.a0001212.pub3

05 / 2013

Cathelicidins

Handbook of Biologically Active Peptides

Mookherjee, N. and Brown, K.L. and Hancock, R.E.W.

DOI: 10.1016/B978-0-12-385095-9.00015-4

Increased intracellular oxygen radical production in neutrophils during febrile episodes of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome

Arthritis and Rheumatism

Sundqvist, M. and Wekell, P. and Osla, V. and Bylund, J. and Christenson, K. and Svman, K. and Foell, D. and Cabral, D.A. and Fasth, A. and Berg, S. and Brown, K.L. and Karlsson, A.

DOI: 10.1002/art.38134

Anti-Inflammatory/Analgesics: An In-Depth Look at p38 MAP Kinases

Pharmaceutical Sciences Encyclopedia

DOI: 10.1002/9780470571224.pse446

Galectin 3 aggravates joint inflammation and destruction in antigen-induced arthritis

Arthritis and Rheumatism

Forsman, H. and Islander, U. and Andrasson, E. and Andersson, A. and nnheim, K. and Karlstrm, A. and Svman, K. and Magnusson, M. and Brown, K.L. and Karlsson, A.

DOI: 10.1002/art.30118

On the road to discovery in periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome

Proceedings of the National Academy of Sciences of the United States of America

Brown, K.L. and Wekell, P. and Karlsson, A. and Berg, S.

DOI: 10.1073/pnas.1107233108

Differential use of chondroitin sulfate to regulate hyaluronan binding by receptor CD44 in inflammatory and interleukin 4-activated macrophages

Journal of Biological Chemistry

Ruffell, B. and Poon, G.F.T. and Lee, S.S.M. and Brown, K.L. and Tjew, S.-L. and Cooper, J. and Johnson, P.

DOI: 10.1074/jbc.M110.200790

Host defense peptide LL-37 selectively reduces proinflammatory macrophage responses

Journal of Immunology

Brown, K.L. and Poon, G.F.T. and Birkenhead, D. and Pena, O.M. and Falsafi, R. and Dahlgren, C. and Karlsson, A. and Bylund, J. and Hancock, R.E.W. and Johnson, P.

DOI: 10.4049/jimmunol.1002508

Intracellular generation of superoxide by the phagocyte NADPH oxidase: How, where, and what for?

Free Radical Biology and Medicine

Bylund, J. and Brown, K.L. and Movitz, C. and Dahlgren, C. and Karlsson, A.

DOI: 10.1016/j.freeradbiomed.2010.09.016

Robust TLR4-induced gene expression patterns are not an accurate indicator of human immunity

Journal of Translational Medicine

Brown, K.L. and Falsafi, R. and Kum, W. and Hamill, P. and Gardy, J.L. and Davidson, D.J. and Turvey, S. and Finlay, B.B. and Speert, D.P. and Hancock, R.E.W.

DOI: 10.1186/1479-5876-8-6

Treating neonatal brain injury - Promise and inherent research challenges

Recent Patents on Inflammation and Allergy Drug Discovery

Svman, K. and Brown, K.L.

DOI: 10.2174/187221310789895586

Profile of blood cells and inflammatory mediators in periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome

BMC Pediatrics

Brown, K.L. and Wekell, P. and Osla, V. and Sundqvist, M. and Svman, K. and Fasth, A. and Karlsson, A. and Berg, S.

DOI: 10.1186/1471-2431-10-65

G-protein-coupled receptor independent, immunomodulatory properties of chemokine CXCL9

Cellular Immunology

Gong, J.-H. and Nicholls, E.F. and Elliott, M.R. and Brown, K.L. and Hokamp, K. and Roche, F.M. and Cheung, C.Y.K. and Falsafi, R. and Brinkman, F.S.L. and Bowdish, D.M.E. and Hancock, R.E.W.

DOI: 10.1016/j.cellimm.2009.11.007

Divergent effects on phagocytosis by macrophage-derived oxygen radicals

Journal of Innate Immunity

Brown, K.L. and Christenson, K. and Karlsson, A. and Dahlgren, C. and Bylund, J.

DOI: 10.1159/000235583

The host defense peptide LL-37 selectively permeabilizes apoptotic leukocytes

Antimicrobial Agents and Chemotherapy

Bjrstad, ?. and Askarieh, G. and Brown, K.L. and Christenson, K. and Foreman, H. and nnheim, K. and Li, H.-N. and Teneberg, S. and Maier, O. and Hoekstra, D. and Dahlgren, C. and Davidson, D.J. and Bylund, J.

DOI: 10.1128/AAC.01310-08

Manual annotation and analysis of the defensin gene cluster in the C57BL/6J mouse reference genome

BMC Genomics

Amid, C. and Rehaume, L.M. and Brown, K.L. and Gilbert, J.G.R. and Dougan, G. and Hancock, R.E.W. and Harrow, J.L.

DOI: 10.1186/1471-2164-10-606

Galectin-3 functions as an opsonin and enhances the macrophage clearance of apoptotic neutrophils

Glycobiology

Karlsson, A. and Christenson, K. and Matlak, M. and Bj?rstad, ?. and Brown, K.L. and Telemo, E. and Salomonsson, E. and Leffler, H. and Bylund, J.

DOI: 10.1093/glycob/cwn104

ROS-deficient monocytes have aberrant gene expression that correlates with inflammatory disorders of chronic granulomatous disease

Clinical Immunology

Brown, K.L. and Bylund, J. and MacDonald, K.L. and Song-Zhao, G.X. and Elliott, M.R. and Falsafi, R. and Hancock, R.E.W. and Speert, D.P.

DOI: 10.1016/j.clim.2008.06.005

Phagocyte-derived reactive oxygen species as suppressors of inflammatory disease

Arthritis and Rheumatism

Bjrkman, L. and Dahlgren, C. and Karlsson, A. and Brown, K.L. and Bylund, J.

DOI: 10.1002/art.23941

Novel anti-infectives: is host defence the answer?

Current Opinion in Biotechnology

Hamill, P. and Brown, K. and Jenssen, H. and Hancock, R.E.

DOI: 10.1016/j.copbio.2008.10.006

Antimicrobial host defense peptides of human neutrophils - Roles in innate immunity

Anti-Infective Agents in Medicinal Chemistry

Bjrstad, ?. and Brown, K.L. and Forsman, H. and Dahlgren, C. and Karlsson, A. and Bylund, J.

DOI: 10.2174/187152108784911278

Is Innate Host Defense the Answer?

Current Opinions in Biotechnology

Hamill P, Jenssen H, Brown KL and Hancock REW (2008) Is Innate Host Defense the Answer? Curr. Opin. Biotech. 19:628-636. PMID 19000763.

PubMed: 19000763

Antimicrobial, Host Defence Peptides and Proteins

eLS

DOI: 10.1002/9780470015902.a0001212.pub2

07 / 2007

Complexities of targeting innate immunity to treat infection

Trends in Immunology

Brown, K.L. and Cosseau, C. and Gardy, J.L. and Hancock, R.E.W.

DOI: 10.1016/j.it.2007.04.005

Enhanced inflammatory responses of chronic granulomatous disease leukocytes involve ROS-independent activation of NF-B

European Journal of Immunology

Bylund, J. and MacDonald, K.L. and Brown, K.L. and Mydel, P. and Collins, L.V. and Hancock, R.E.W. and Speert, D.P.

DOI: 10.1002/eji.200636651

Bovine and human cathelicidin cationic host defense peptides similarly suppress transcriptional responses to bacterial lipopolysaccharide

Journal of Leukocyte Biology

Mookherjee, N. and Wilson, H.L. and Doria, S. and Popowych, Y. and Falsafi, R. and Yu, J. and Li, Y. and Veatch, S. and Roche, F.M. and Brown, K.L. and Brinkman, F.S.L. and Hokamp, K. and Potter, A. and Babiuk, L.A. and Griebel, P.J. and Hancock, R.E.W.

DOI: 10.1189/jlb.0106048

IRAK-4 mutation (Q293X): Rapid detection and characterization of defective post-transcriptional TLR/IL-1R responses in human myeloid and non-myeloid cells

Journal of Immunology

Davidson, D.J. and Currie, A.J. and Bowdish, D.M.E. and Brown, K.L. and Rosenberger, C.M. and Ma, R.C. and Bylund, J. and Campsall, P.A. and Puel, A. and Picard, C. and Casanova, J.-L. and Turvey, S.E. and Hancock, R.E.W. and Devon, R.S. and Speert, D.P.

DOI: 10.4049/jimmunol.177.11.8202

Cationic host defense (antimicrobial) peptides

Current Opinion in Immunology

Brown, K.L. and Hancock, R.E.W.

DOI: 10.1016/j.coi.2005.11.004

Modulation of the TLR-mediated inflammatory response by the endogenous human host defense peptide LL-37

Journal of Immunology

Mookherjee, N. and Brown, K.L. and Bowdish, D.M.E. and Doria, S. and Falsafi, R. and Hokamp, K. and Roche, F.M. and Mu, R. and Doho, G.H. and Pistolic, J. and Powers, J.-P. and Bryan, J. and Brinkman, F.S.L. and Hancock, R.E.W.

DOI: 10.4049/jimmunol.176.4.2455

Host defence peptides from invertebrates - emerging antimicrobial strategies

Immunobiology

Hancock, R.E.W. and Brown, K.L. and Mookherjee, N.

DOI: 10.1016/j.imbio.2005.10.017

Cathelicidins: Cationic Host Defense and Antimicrobial Peptides

Handbook of Biologically Active Peptides

Mookherjee, N. and Brown, K.L. and Hancock, R.E.W.

DOI: 10.1016/B978-012369442-3/50015-5

Regulation of hyaluronan binding by F-actin and colocalization of CD44 and phosphorylated ezrin/radixin/moesin (ERM) proteins in myeloid cells

Experimental Cell Research

Brown, K.L. and Birkenhead, D. and Lai, J.C.Y. and Li, L. and Li, R. and Johnson, P.

DOI: 10.1016/j.yexcr.2004.10.002

Expression of N-acetylglucosamine 6-O-sulfotransferases (GlcNAc6STs)-1 and -4 in human monocytes: GlcNAc6ST-1 is implicated in the generation of the 6-sulfo N-acetyllactosamine/Lewis x epitope on CD44 and is induced by TNF-alpha

Glycobiology

Tjew, S.L. and Brown, K.L. and Kannagi, R. and Johnson, P.

DOI: 10.1093/glycob/cwi050

Role of sulfation in CD44-mediated hyaluronan binding induced by inflammatory mediators in human CD14+ peripheral blood monocytes

Journal of Immunology

Brown, K.L. and Maiti, A. and Johnson, P.

DOI: 10.4049/jimmunol.167.9.5367

A role for the cell adhesion molecule CD44 and sulfation in leukocyte-endothelial cell adhesion during an inflammatory response?

Biochemical Pharmacology

Johnson, P. and Maiti, A. and Brown, K.L. and Li, R.

DOI: 10.1016/S0006-2952(99)00266-X

Assaying phage-borne peptides by phage capture on fibrinogen or streptavidin.

Biological chemistry

Bonnycastle LL and Brown KL and Tang J and Scott JK

DOI: 10.1515/bchm.1997.378.6.509 PubMed: 9224931

06 / 1997

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.

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.

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.

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Congratulations CIHR Fall 2021 Project Grant Recipients!
Congratulations to the BC Children's Hospital Research Institute (BCCHR) and Women’s Health Research Institute (WHRI) investigators and their teams who were awarded funding through the Canadian Institutes of Health Research (CIHR) Fall 2021 Project Grant competition. Our research community received around $6 million in new research grants as principal investigators or co-investigators.
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At BC Children’s, we are making discoveries that save lives and transform health care for children in our province and around the world. Our research portfolio includes basic, clinical, population, and public health research.

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Kelly Brown

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Investigator, BC Children's Hospital

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Evaluating Renal Disease in Pediatric-Onset Antineutrophil Cytoplasmic Antibody"Associated Vasculitis: Disease Course, Outcomes, and Predictors of Outcome

No-lyse no-wash flow cytometry method for ex vivo study of human neutrophils

Comparing Rituximab and Cyclophosphamide in Induction Therapy for Childhood-Onset Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis: An ARChiVe Registry Cohort Study

Anti-LAMP-2 Antibody Seropositivity in Children with Primary Systemic Vasculitis Affecting Medium- and Large-Sized Vessels

Predictive utility of ANCA positivity and antigen specificity in the assessment of kidney disease in paediatric-onset small vessel vasculitis

Editorial: Innate immunity in vasculitis

Elevated ADA2 Enzyme Activity at the Onset of Chronic Graft-versus-Host Disease in Children

Hyaluronan promotes intracellular ROS production and apoptosis in TNFa-stimulated neutrophils

Behets syndrome: recent advances to aid diagnosis

Association Between HLA"DPB1 and Antineutrophil Cytoplasmic Antibody"Associated Vasculitis in Children

Pathogenic variant c.1052T>A (p.Leu351Gln) in adenosine deaminase 2 impairs secretion and elevates type I IFN responsive gene expression

Galectin-3 Modulates Microglia Inflammation in vitro but Not Neonatal Brain Injury in vivo under Inflammatory Conditions

Latent gammaherpesvirus exacerbates arthritis and requires age-associated B cells

Children with systemic autoinflammatory diseases have multiple, mixed ethnicities that reflect regional ethnic diversity

Different Disease Endotypes in Phenotypically Similar Vasculitides Affecting Small-to-Medium Sized Blood Vessels

Autoantibodies Against Lysosome Associated Membrane Protein-2 (LAMP-2) in Pediatric Chronic Primary Systemic Vasculitis

Latent gammaherpesvirus exacerbates arthritis through modification of age-associated b cells

Adenosine deaminase 2 activity negatively correlates with age during childhood

Anti-neutrophil cytoplasmic antibodies (ANCA): Antigen interactions and downstream effects

Hyaluronan primes the oxidative burst in human neutrophils

Consensus treatment plans for periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome (PFAPA): A framework to evaluate treatment responses from the childhood arthritis and rheumatology research alliance (CARRA) PFAPA work group

Methods for type I interferon detection and their relevance for clinical utility and improved understanding of rheumatic diseases.

Monocyte-Derived Interleukin-1 As the Driver of S100A12-Induced Sterile Inflammatory Activation of Human Coronary Artery Endothelial Cells: Implications for the Pathogenesis of Kawasaki Disease

Complexity in unclassified auto-inflammatory disease: A case report illustrating the potential for disease arising from the allelic burden of multiple variants

Comparable type i interferon score determination from PAXgene and Tempus whole blood RNA collection and isolation systems

Methods for type I interferon detection and their relevance for clinical utility and improved understanding of rheumatic diseases

Periodic fever syndromes: Beyond the single gene paradigm

Identification of Novel Adenosine Deaminase 2 Gene Variants and Varied Clinical Phenotype in Pediatric Vasculitis

The value of creativity for enhancing translational ecologies, insights, and discoveries

Measles Lymphadenopathy in a Child With PFAPA Syndrome

S100A12 Serum Levels and PMN counts are elevated in childhood systemic vasculitides especially involving proteinase 3 specific anti-neutrophil cytoplasmic antibodies

The importance of considering monogenic causes of autoimmunity: A somatic mutation in KRAS causing pediatric Rosai-Dorfman syndrome and systemic lupus erythematosus

Elevated mitochondrial reactive oxygen species and cellular redox imbalance in human NADPH-oxidase-deficient phagocytes

Clinical practice variation and need for pediatric-specific treatment guidelines among rheumatologists caring for children with ANCA-associated vasculitis: An international clinician survey

Endotoxin free hyaluronan and hyaluronan fragments do not stimulate TNF-a, interleukin-12 or upregulate co-stimulatory molecules in dendritic cells or macrophages

Temporal characterization of microglia/macrophage phenotypes in a mouse model of neonatal hypoxic-ischemic brain injury

Purified hyaluronan and hyaluronan fragments do not stimulate pro-inflammatory cytokine production in dendritic cells or macrophages

The where, when, how and why of hyaluronan binding by immune cells

Pediatric vasculitis: Advances in treatment

Innate defense regulator peptide 1018 protects against perinatal brain injury

Host Defence (Antimicrobial) Peptides and Proteins

Cathelicidins

Increased intracellular oxygen radical production in neutrophils during febrile episodes of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome

Anti-Inflammatory/Analgesics: An In-Depth Look at p38 MAP Kinases

Galectin 3 aggravates joint inflammation and destruction in antigen-induced arthritis

On the road to discovery in periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome

Differential use of chondroitin sulfate to regulate hyaluronan binding by receptor CD44 in inflammatory and interleukin 4-activated macrophages

Host defense peptide LL-37 selectively reduces proinflammatory macrophage responses

Intracellular generation of superoxide by the phagocyte NADPH oxidase: How, where, and what for?

Robust TLR4-induced gene expression patterns are not an accurate indicator of human immunity

Treating neonatal brain injury - Promise and inherent research challenges

Profile of blood cells and inflammatory mediators in periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome

G-protein-coupled receptor independent, immunomodulatory properties of chemokine CXCL9

Divergent effects on phagocytosis by macrophage-derived oxygen radicals

The host defense peptide LL-37 selectively permeabilizes apoptotic leukocytes

Manual annotation and analysis of the defensin gene cluster in the C57BL/6J mouse reference genome

Galectin-3 functions as an opsonin and enhances the macrophage clearance of apoptotic neutrophils

ROS-deficient monocytes have aberrant gene expression that correlates with inflammatory disorders of chronic granulomatous disease

Phagocyte-derived reactive oxygen species as suppressors of inflammatory disease

Novel anti-infectives: is host defence the answer?

Antimicrobial host defense peptides of human neutrophils - Roles in innate immunity

Is Innate Host Defense the Answer?

Antimicrobial, Host Defence Peptides and Proteins

Complexities of targeting innate immunity to treat infection

Enhanced inflammatory responses of chronic granulomatous disease leukocytes involve ROS-independent activation of NF-B

Bovine and human cathelicidin cationic host defense peptides similarly suppress transcriptional responses to bacterial lipopolysaccharide

IRAK-4 mutation (Q293X): Rapid detection and characterization of defective post-transcriptional TLR/IL-1R responses in human myeloid and non-myeloid cells

Cationic host defense (antimicrobial) peptides

Modulation of the TLR-mediated inflammatory response by the endogenous human host defense peptide LL-37

Host defence peptides from invertebrates - emerging antimicrobial strategies

Cathelicidins: Cationic Host Defense and Antimicrobial Peptides