- Overview
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Macrophages are specialized cells of our immune system. They provide our first line of defence against invading micro-organisms starting the immune response and are called “killer” macrophages. When our body has finished killing off unwanted invaders, these macrophages change their function and help in cleaning up the injured area. These are called “healer” macrophages. During clean up, macrophages tidy up debris, promote wound healing and scar formation and shut off the immune response. In some inflammatory diseases, like inflammatory bowel disease, the immune response gets out of control. Macrophages are the largest producers of tumour necrosis factor alpha in the gut and an antibody directed against this macrophage product is an effective therapy for patients with Crohn’s disease and ulcerative colitis. The goal of my research is to understand how these macrophages make the switch from “killers” to “healers” with the hope of pushing macrophages to “healers” during inflammatory bowel disease
- Publications
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Alleviation of severe chronic arthritic pain using polyvalent immunoglobulins (KMP01): Two case reports
International Journal of Clinical Pharmacology and Therapeutics
DOI: 10.5414/CP204615
2024Macrophage immunotherapy: overcoming impediments to realize promise
Trends in Immunology
Sly, L.M. and McKay, D.M.
DOI: 10.1016/j.it.2022.10.002
2022Evidence that oral immunoglobulins (KMP01) suppress pro-tumor inflammation in rectal carcinoma: Case report and treatment concept
International Journal of Clinical Pharmacology and Therapeutics
DOI: 10.5414/CP204326
2022A188 TARGETING RIPK2 TO TREAT INTESTINAL INFLAMMATION CAUSED BY SHIP DEFICIENCY
Journal of the Canadian Association of Gastroenterology
Pang Y and Menzies S and Baksh S and Sly L
03/2021Vedolizumab: Potential Mechanisms of Action for Reducing Pathological Inflammation in Inflammatory Bowel Diseases.
Frontiers in cell and developmental biology
Luzentales-Simpson M and Pang YCF and Zhang A and Sousa JA and Sly LM
DOI: 10.3389/fcell.2021.612830
PubMed: 33614645
02/2021COVID-19: Cytokine storm modulation/blockade with oral polyvalent immunoglobulins (PVIG, KMP01D): A potential and safe therapeutic agent (Primum nil nocere).
International journal of clinical pharmacology and therapeutics
Sly LM and Braun P and Woodcock BG
DOI: 10.5414/cp203890
PubMed: 33141018
12/2020A202 DYSREGULATED ENDOPLASMIC RETICULUM STRESS PATHWAYS IN COLON-DERIVED ENTEROIDS FROM INFLAMMATORY BOWEL DISEASE PATIENTS DRIVE DC MATURATION LEADING TO A PRO-INFLAMMATORY PHENOTYPE.
Journal of the Canadian Association of Gastroenterology
Rees WD and Stahl M and Jacobson K and Bressler B and Sly LM and Vallance B and Steiner T
DOI: 10.1093/jcag/gwz047.201
02/2020A10 TR1 CELL-BASED THERAPY FOR INFLAMMATORY ILEITIS IN SHIP-/- MICE.
Journal of the Canadian Association of Gastroenterology
Lisko D and Menzies S and Sly LM and Steiner T
DOI: 10.1093/jcag/gwz047.009
02/2020Enteroids derived from inflammatory bowel disease patients display dysregulated endoplasmic reticulum stress pathways, leading to differential inflammatory responses and dendritic cell maturation
Journal of Crohn's and Colitis
Rees, W.D. and Stahl, M. and Jacobson, K. and Bressler, B. and Sly, L.M. and Vallance, B.A. and Steiner, T.S.
DOI: 10.1093/ECCO-JCC/JJZ194
2020How do immune and mesenchymal cells influence the intestinal epithelial cell compartment in inflammatory bowel disease? Let's crosstalk about it!
Journal of Leukocyte Biology
Rees, W.D. and Sly, L.M. and Steiner, T.S.
DOI: 10.1002/JLB.3MIR0120-567R
2020FcRn is a CD32a coreceptor that determines susceptibility to IgG immune complex-driven autoimmunity
The Journal of experimental medicine
Hubbard, J.J. and Pyzik, M. and Rath, T. and Kozicky, L.K. and Sand, K.M.K. and Gandhi, A.K. and Grevys, A. and Foss, S. and Menzies, S.C. and Glickman, J.N. and Fiebiger, E. and Roopenian, D.C. and Sandlie, I. and Andersen, J.T. and Sly, L.M. and Baker, K. and Blumberg, R.S.
DOI: 10.1084/jem.20200359
2020Gut microbes in pediatric ALL survivorship
Pediatric Hematology and Oncology
Sly, L.M.
DOI: 10.1080/08880018.2020.1793850
2020Intravenous immunoglobulin (IVIg) or IVIg-treated macrophages reduce DSS-induced colitis by inducing macrophage IL-10 production
European Journal of Immunology
Kozicky, L.K. and Menzies, S.C. and Hotte, N. and Madsen, K.L. and Sly, L.M.
DOI: 10.1002/eji.201848014
2019Malt1 deficient mice develop osteoporosis independent of osteoclast-intrinsic effects of Malt1 deficiency
Journal of Leukocyte Biology
Monajemi, M. and Fisk, S. and Pang, Y.C.F. and Leung, J. and Menzies, S.C. and Ben-Othman, R. and Cai, B. and Kollmann, T.R. and Rozmus, J. and Sly, L.M.
DOI: 10.1002/JLB.5VMA0219-054R
2019Compositional changes to the ileal microbiome precede the onset of spontaneous ileitis in SHIP deficient mice
Gut Microbes
Dobranowski, P.A. and Tang, C. and Sauvé, J.P. and Menzies, S.C. and Sly, L.M.
DOI: 10.1080/19490976.2018.1560767
2019Integrins and ERp57 coordinate to regulate cell surface calreticulin in immunogenic cell death
Frontiers in Oncology
Liu, C.-C. and Leclair, P. and Pedari, F. and Vieira, H. and Monajemi, M. and Sly, L.M. and Reid, G.S. and Lim, C.J.
DOI: 10.3389/fonc.2019.00411
2019Phosphatidylinositol 3-kinase p110d drives intestinal fibrosis in SHIP deficiency
Mucosal Immunology
Lo, Y. and Sauve, J.P. and Menzies, S.C. and Steiner, T.S. and Sly, L.M.
DOI: 10.1038/s41385-019-0191-z
2019A80 MALT1 BLOCKS IL-1ß-MEDIATED INTESTINAL INFLAMMATION.
Journal of the Canadian Association of Gastroenterology
Monajemi M and Pang Y and Menzies S and Sly LM
DOI: 10.1093/jcag/gwy009.080
02/2018A7 PI3KP110d DRIVES INTESTINAL FIBROSIS IN SHIP DEFICIENT MICE.
Journal of the Canadian Association of Gastroenterology
Lo Y and Sauvé J and Menzies S and Sly LM
DOI: 10.1093/jcag/gwy008.008
02/2018A94 SHIP-MICROBIOME INTERACTIONS IN INTESTINAL INFLAMMATION.
Journal of the Canadian Association of Gastroenterology
Dobranowski P and Menzies S and Sly LM
DOI: 10.1093/jcag/gwy009.094
02/2018CD47-ligation induced cell death in T-acute lymphoblastic leukemia article
Cell Death and Disease
Leclair, P. and Liu, C.-C. and Monajemi, M. and Reid, G.S. and Sly, L.M. and Lim, C.J.
DOI: 10.1038/s41419-018-0601-2
2018SHIP negatively regulates type II immune responses in mast cells and macrophages
Journal of Leukocyte Biology
Dobranowski, P. and Sly, L.M.
DOI: 10.1002/JLB.3MIR0817-340R
2018Inflammatory bowel disease and immunonutrition: novel therapeutic approaches through modulation of diet and the gut microbiome
Immunology
Celiberto, L.S. and Graef, F.A. and Healey, G.R. and Bosman, E.S. and Jacobson, K. and Sly, L.M. and Vallance, B.A.
DOI: 10.1111/imm.12939
2018Malt1 blocks IL-1ß production by macrophages in vitro and limits dextran sodium sulfate-induced intestinal inflammation in vivo
Journal of Leukocyte Biology
Monajemi, M. and Pang, Y.C.F. and Bjornson, S. and Menzies, S.C. and van Rooijen, N. and Sly, L.M.
DOI: 10.1002/JLB.3VMA0118-019R
2018IVIg and LPS co-stimulation induces IL-10 production by human monocytes, which is compromised by an Fc¿RIIA disease-associated gene variant
Frontiers in Immunology
Kozicky, L.K. and Menzies, S.C. and Zhao, Z.Y. and Vira, T. and Harnden, K. and Safari, K. and Del Bel, K.L. and Turvey, S.E. and Sly, L.M.
DOI: 10.3389/fimmu.2018.02676
2018IFN-¿ directly inhibits murine B-cell precursor leukemia-initiating cell proliferation early in life
European Journal of Immunology
Fidanza, M. and Seif, A.E. and Jo, S. and Kariminia, A. and Rolf, N. and Sly, L.M. and Grupp, S.A. and Reid, G.S.D.
DOI: 10.1002/eji.201646806
2017Assessment of antibody-based drugs effects on murine bone marrow and peritoneal macrophage activation
Journal of Visualized Experiments
Kozicky, L. and Sly, L.M.
DOI: 10.3791/56689
2017Endosomal pH modulation by peptide-gold nanoparticle hybrids enables potent anti-inflammatory activity in phagocytic immune cells
Biomaterials
Yang, H. and Kozicky, L. and Saferali, A. and Fung, S.-Y. and Afacan, N. and Cai, B. and Falsafi, R. and Gill, E. and Liu, M. and Kollmann, T.R. and Hancock, R.E.W. and Sly, L.M. and Turvey, S.E.
DOI: 10.1016/j.biomaterials.2016.09.032
2016a-Integrin expression and function modulates presentation of cell surface calreticulin
Cell Death and Disease
Liu, C.-C. and Leclair, P. and Monajemi, M. and Sly, L.M. and Reid, G.S. and Lim, C.J.
DOI: 10.1038/cddis.2016.176
2016Activity of SHIP, Which Prevents Expression of Interleukin 1ß, Is Reduced in Patients with Crohn's Disease
Gastroenterology
Ngoh, E.N. and Weisser, S.B. and Lo, Y. and Kozicky, L.K. and Jen, R. and Brugger, H.K. and Menzies, S.C. and McLarren, K.W. and Nackiewicz, D. and Van Rooijen, N. and Jacobson, K. and Ehses, J.A. and Turvey, S.E. and Sly, L.M.
DOI: 10.1053/j.gastro.2015.09.049
2016The Crohn's disease-associated polymorphism in ATG16L1 (rs2241880) reduces SHIP gene expression and activity in human subjects
Genes and Immunity
Ngoh, E.N. and Brugger, H.K. and Monajemi, M. and Menzies, S.C. and Hirschfeld, A.F. and Del Bel, K.L. and Jacobson, K. and Lavoie, P.M. and Turvey, S.E. and Sly, L.M.
DOI: 10.1038/gene.2015.30
2015Phosphatase regulation of macrophage activation
Seminars in Immunology
Kozicky, L.K. and Sly, L.M.
DOI: 10.1016/j.smim.2015.07.001
2015Impaired NLRP3 inflammasome activity during fetal development regulates IL-1ß production in human monocytes
European Journal of Immunology
Sharma, A.A. and Jen, R. and Kan, B. and Sharma, A. and Marchant, E. and Tang, A. and Gadawski, I. and Senger, C. and Skoll, A. and Turvey, S.E. and Sly, L.M. and Côté, H.C.F. and Lavoie, P.M.
DOI: 10.1002/eji.201444707
2015Intravenous immunoglobulin skews macrophages to an anti-inflammatory, IL-10-producing activation state
Journal of Leukocyte Biology
Kozicky, L.K. and Zhao, Z.Y. and Menzies, S.C. and Fidanza, M. and Reid, G.S.D. and Wilhelmsen, K. and Hellman, J. and Hotte, N. and Madsen, K.L. and Sly, L.M.
DOI: 10.1189/jlb.3VMA0315-078R
2015Combined immunodeficiency associated with homozygous MALT1 mutations
Journal of Allergy and Clinical Immunology
McKinnon, M.L. and Rozmus, J. and Fung, S.-Y. and Hirschfeld, A.F. and Del Bel, K.L. and Thomas, L. and Marr, N. and Martin, S.D. and Marwaha, A.K. and Priatel, J.J. and Tan, R. and Senger, C. and Tsang, A. and Prendiville, J. and Junker, A.K. and Seear, M. and Schultz, K.R. and Sly, L.M. and Holt, R.A. and Patel, M.S. and Friedman, J.M. and Turvey, S.E.
DOI: 10.1016/j.jaci.2013.10.045
2014Arginase activity in alternatively activated macrophages protects PI3Kp110d deficient mice from dextran sodium sulfate induced intestinal inflammation
European Journal of Immunology
Weisser, S.B. and Kozicky, L.K. and Brugger, H.K. and Ngoh, E.N. and Cheung, B. and Jen, R. and Menzies, S.C. and Samarakoon, A. and Murray, P.J. and Lim, C.J. and Johnson, P. and Boucher, J.-L. and van Rooijen, N. and Sly, L.M.
DOI: 10.1002/eji.201343981
2014Generation and characterization of murine alternatively activated macrophages
Methods in Molecular Biology
Weisser, S.B. and McLarren, K.W. and Kuroda, E. and Sly, L.M.
DOI: 10.1007/978-1-62703-128-8-14
2013Mutant IDH1 promotes leukemogenesis in vivo and can be specifically targeted in human AML
Blood
Chaturvedi, A. and Araujo Cruz, M.M. and Jyotsana, N. and Sharma, A. and Yun, H. and Görlich, K. and Wichmann, M. and Schwarzer, A. and Preller, M. and Thol, F. and Meyer, J. and Haemmerle, R. and Struys, E.A. and Jansen, E.E. and Modlich, U. and Li, Z. and Sly, L.M. and Geffers, R. and Lindner, R. and Manstein, D.J. and Lehmann, U. and Krauter, J. and Ganser, A. and Heuser, M.
DOI: 10.1182/blood-2013-03-491571
2013Generation and characterization of murine alternatively activated macrophages.
Weisser SB and McLarren KW and Kuroda E and Sly LM
DOI: 10.1007/978-1-62703-128-8_14
PubMed: 23179835
2013Depletion and reconstitution of macrophages in mice
Journal of Visualized Experiments
Weisser, S.B. and van Rooijen, N. and Sly, L.M.
DOI: 10.3791/4105
2012Alternative activation of macrophages by IL-4 requires SHIP degradation
European Journal of Immunology
Weisser, S.B. and Mclarren, K.W. and Voglmaier, N. and van Netten-Thomas, C.J. and Antov, A. and Flavell, R.A. and Sly, L.M.
DOI: 10.1002/eji.201041105
2011A low carbohydrate, high protein diet slows tumor growth and prevents cancer initiation
Cancer Research
Ho, V.W. and Leung, K. and Hsu, A. and Luk, B. and Lai, J. and Shen, S.Y. and Minchinton, A.I. and Waterhouse, D. and Bally, M.B. and Lin, W. and Nelson, B.H. and Sly, L.M. and Krystal, G.
DOI: 10.1158/0008-5472.CAN-10-3973
2011SHIP-deficient, alternatively activated macrophages protect mice during DSS-induced colitis
Journal of Leukocyte Biology
Weisser, S.B. and Brugger, H.K. and Voglmaier, N.S. and McLarren, K.W. and van Rooijen, N. and Sly, L.M.
DOI: 10.1189/jlb.0311124
2011SHIP represses Th2 skewing by inhibiting IL-4 production from basophils
Journal of Immunology
Kuroda, E. and Antignano, F. and Ho, V.W. and Hughes, M.R. and Ruschmann, J. and Lam, V. and Kawakami, T. and Kerr, W.G. and McNagny, K.M. and Sly, L.M. and Krystal, G.
DOI: 10.4049/jimmunol.1002778
2011SHIP-deficient mice develop spontaneous intestinal inflammation and arginase-dependent fibrosis
American Journal of Pathology
McLarren, K.W. and Cole, A.E. and Weisser, S.B. and Voglmaier, N.S. and Conlin, V.S. and Jacobson, K. and Popescu, O. and Boucher, J.-L. and Sly, L.M.
DOI: 10.1016/j.ajpath.2011.03.018
2011Tyrosine phosphorylation of SHIP promotes its proteasomal degradation
Experimental Hematology
Ruschmann, J. and Ho, V. and Antignano, F. and Kuroda, E. and Lam, V. and Ibaraki, M. and Snyder, K. and Kim, C. and Flavell, R.A. and Kawakami, T. and Sly, L. and Turhan, A.G. and Krystal, G.
DOI: 10.1016/j.exphem.2010.03.010
2010The p110a and p110ß isoforms of class i phosphatidylinositol 3-kinase are involved in toll-like receptor 5 signaling in epithelial cells
Mediators of Inflammation
Ivison, S.M. and Khan, M.A.S. and Graham, N.R. and Shobab, L.A. and Yao, Y. and Kifayet, A. and Sly, L.M. and Steiner, T.S.
DOI: 10.1155/2010/652098
2010Derivation and characterization of murine alternatively activated (m2) macrophages
Methods in Molecular Biology
Ho, V.W.H. and Sly, L.M.
DOI: 10.1007/978-1-59745-396-7_12
2009SHIP prevents lipopolysaccharide from triggering an antiviral response in mice
Blood
Sly, L.M. and Hamilton, M.J. and Kuroda, E. and Ho, V.W. and Antignano, F.L. and Omeis, S.L. and Van Netten-Thomas, C.J. and Wong, D. and Brugger, H.K. and Williams, O. and Feldman, M.E. and Houseman, B.T. and Fiedler, D. and Shokat, K.M. and Krystal, G.
DOI: 10.1182/blood-2008-06-166082
2009Modeling the functional heterogeneity of leukemia stem cells: Role of STAT5 in leukemia stem cell self-renewal
Blood
Heuser, M. and Sly, L.M. and Argiropoulos, B. and Kuchenbauer, F. and Lai, C. and Weng, A. and Leung, M. and Lin, G. and Brookes, C. and Fung, S. and Valk, P.J. and Delwel, R. and Löwenberg, B. and Krystal, G. and Humphries, R.K.
DOI: 10.1182/blood-2009-06-227603
2009The Src Homology 2 Containing Inositol 5' Phosphatases
Handbook of Cell Signaling, Second Edition
DOI: 10.1016/B978-0-12-374145-5.00134-0
2009SHIP represses the generation of IL-3-induced M2 macrophages by inhibiting IL-4 production from basophils
Journal of Immunology
Kuroda, E. and Ho, V. and Ruschmann, J. and Antignano, F. and Hamilton, M. and Rauh, M.J. and Antov, A. and Flavell, R.A. and Sly, L.M. and Krystal, G.
DOI: 10.4049/jimmunol.0900864
2009SHIP regulates the reciprocal development of T regulatory and Th17 cells
Journal of Immunology
Locke, N.R. and Patterson, S.J. and Hamilton, M.J. and Sly, L.M. and Krystal, G. and Levings, M.K.
DOI: 10.4049/jimmunol.0803749
2009Linkage of Meis1 leukemogenic activity to multiple downstream effectors including Trib2 and Ccl3
Experimental Hematology
Argiropoulos, B. and Palmqvist, L. and Yung, E. and Kuchenbauer, F. and Heuser, M. and Sly, L.M. and Wan, A. and Krystal, G. and Humphries, R.K.
DOI: 10.1016/j.exphem.2008.02.011
2008The inositol phosphatase SHIP controls Salmonella enterica serovar typhimurium infection in vivo
Infection and Immunity
Bishop, J.L. and Sly, L.M. and Krystal, G. and Finlay, B.B.
DOI: 10.1128/IAI.01596-07
2008IgE-induced mast cell survival requires the prolonged generation of reactive oxygen species
Journal of Immunology
Sly, L.M. and Kalesnikoff, J. and Lam, V. and Wong, D. and Song, C. and Omeis, S. and Chan, K. and Lee, C.W.K. and Siraganian, R.P. and Rivera, J. and Krystal, G.
DOI: 10.4049/jimmunol.181.6.3850
2008Re: The terminology issue for myeloid-derived suppressor cells
Cancer Research
Krystal, G. and Sly, L. and Antignano, F. and Ho, V. and Ruschmann, J. and Hamilton, M.
DOI: 10.1158/0008-5472.CAN-07-0211
2007Monocyte p110a phosphatidylinositol 3-kinase regulates phagocytosis, the phagocyte oxidase, and cytokine production
Journal of Leukocyte Biology
Lee, J.S. and Nauseef, W.M. and Moeenrezakhanlou, A. and Sly, L.M. and Noubir, S. and Leidal, K.G. and Schlomann, J.M. and Krystal, G. and Reiner, N.E.
DOI: 10.1189/jlb.0906564
2007The role of SHIP in macrophages
Frontiers in Bioscience
Sly, L.M. and Ho, V. and Antignano, F. and Ruschmann, J. and Hamilton, M. and Lam, V. and Rauh, M.J. and Krystal, G.
DOI: 10.2741/2276
2007The Flt3 receptor tyrosine kinase collaborates with NUP98-HOX fusions in acute myeloid leukemia
Blood
Palmqvist, L. and Argiropoulos, B. and Pineault, N. and Abramovich, C. and Sly, L.M. and Krystal, G. and Wan, A. and Humphries, R.K.
DOI: 10.1182/blood-2005-12-007005
2006SHIP represses the generation of alternatively activated macrophages
Immunity
Rauh, M.J. and Ho, V. and Pereira, C. and Sham, A. and Sly, L.M. and Lam, V. and Huxham, L. and Minchinton, A.I. and Mui, A. and Krystal, G.
DOI: 10.1016/j.immuni.2005.09.003
2005The role of SHIP1 in macrophage programming and activation.
Rauh MJ and Sly LM and Kalesnikoff J and Hughes MR and Cao LP and Lam V and Krystal G
PubMed: 15494015
11/2004The role of SHIP1 in macrophage programming and activation
Biochemical Society Transactions
DOI: 10.1042/BST0320785
2004LPS-induced upregulation of SHIP is essential for endotoxin tolerance
Immunity
Sly, L.M. and Rauh, M.J. and Kalesnikoff, J. and Song, C.H. and Krystal, G.
DOI: 10.1016/j.immuni.2004.07.010
2004Role of Src homology 2-containing-inositol 5'-phosphatase (SHIP) in mast cells and macrophages.
Rauh MJ and Kalesnikoff J and Hughes M and Sly L and Lam V and Krystal G
PubMed: 12546703
02/2003The 19-kDa Mycobacterium tuberculosis protein induces macrophage apoptosis through toll-like receptor-2
Journal of Immunology
López, M. and Sly, L.M. and Luu, Y. and Young, D. and Cooper, H. and Reiner, N.E.
DOI: 10.4049/jimmunol.170.5.2409
2003The role of SHIP in cytokine-induced signaling.
Reviews of physiology, biochemistry and pharmacology
Kalesnikoff, J. and Sly, L.M. and Hughes, M.R. and Büchse, T. and Rauh, M.J. and Cao, L.P. and Lam, V. and Mui, A. and Huber, M. and Krystal, G.
2003Survival of Mycobacterium tuberculosis in host macrophages involves resistance to apoptosis dependent upon induction of antiapoptotic Bcl-2 family member Mcl-1
Journal of Immunology
Sly, L.M. and Hingley-Wilson, S.M. and Reiner, N.E. and McMaster, W.R.
DOI: 10.4049/jimmunol.170.1.430
2003Role of Src homology 2-containing-inositol 5'-phosphatase (SHIP) in mast cells and macrophages
Biochemical Society Transactions
DOI: 10.1042/bst0310286
2003SHIP, SHIP2, and PTEN activities are regulated in vivo by modulation of their protein levels: SHIP is up-regulated in macrophages and mast cells by lipopolysaccharide
Experimental Hematology
Sly, L.M. and Rauh, M.J. and Kalesnikoff, J. and Büchse, T. and Krystal, G.
DOI: 10.1016/j.exphem.2003.09.011
2003Salmonella enterica serovar Typhimurium periplasmic superoxide dismutases SodCI and SodCII are required for protection against the phagocyte oxidative burst
Infection and Immunity
Sly, L.M. and Guiney, D.G. and Reiner, N.E.
DOI: 10.1128/IAI.70.9.5312-5315.2002
20021a,25-Dihydroxyvitamin D
3 -induced Monocyte Antimycobacterial Activity is Regulated by Phosphatidylinositol 3-Kinase and Mediated by the NADPH-dependent Phagocyte Oxidase
Journal of Biological Chemistry
Sly, L.M. and Lopez, M. and Nauseef, W.M. and Reiner, N.E.
DOI: 10.1074/jbc.M102876200
20011a,25-dihydroxyvitamin D
3 -induced myeloid cell differentiation is regulated by a vitamin D receptor-phosphatidylinositol 3-kinase signaling complex
Journal of Experimental Medicine
Hmama, Z. and Nandan, D. and Sly, L. and Knutson, K.L. and Herrera-Velit, P. and Reiner, N.E.
DOI: 10.1084/jem.190.11.1583
1999Reconstitution of glucose uptake and chemotaxis in Pseudomonas aeruginosa glucose transport defective mutants.
Sly LM and Worobec EA and Perkins RE and Phibbs PV
PubMed: 8306210
11/1993Reconstitution of glucose uptake and chemotaxis in Pseudomonas aeruginosa glucose transport defective mutants
Canadian Journal of Microbiology
Sly, L.M. and Worobec, E.A. and Perkins, R.E. and Phibbs Jr., P.V.
DOI: 10.1139/m93-163
1993 - Research
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Macrophage phenotype in inflammatory bowel disease
Macrophages are critical effector cells in the inflammatory response. Classically activated macrophages initiate the innate immune response and direct the activity of the acquired immune response. Upon resolution of inflammation, macrophages convert to an anti-inflammatory phenotype called alternatively activated. Alternatively activated macrophages promote debris scavenging, tissue remodelling and wound healing. Intriguingly, macrophages can be manipulated to move back and forth between these two phenotypes. During inflammatory disorders, like inflammatory bowel disease, switching macrophages to an alternatively activated phenotype, could dampen down inflammation and reduce disease. We are currently assessing the macrophage phenotype present during inflammatory bowel disease and mechanisms that we could use to switch macrophages to an anti-inflammatory phenotype during disease.L-arginine metabolism in inflammation and fibrosis
L-arginine metabolism provides a key switch in macrophage phenotype. L-arginine can be metabolized by two pathways in macrophages. In classically activated macrophages during inflammation, the enzyme inducible nitric oxide synthase (iNOS) uses arginine to generate pro-inflammatory nitric oxide (NO). However, alternatively activated macrophages also express the enzyme arginase. Arginase metabolizes arginine leading to the production of polyamines, which promote cell growth, and proline, an essential component of collagen that can contribute to fibrosis. We are currently investigating the role of arginine metabolism by each of these pathways in inflammation and in fibrosis.Role of the PI3K pathway in canonical alternative activation of macrophages
The src homology 2 domain-containing inositol 5'-phosphatase (SHIP) is a negative regulator of the phosphatidylinositol 3-kinase (PI3K) pathway. In vivo-differentiated SHIP deficient macrophages display a profoundly anergic phenotype and express phenotypic markers of alternative activation independent of canonical skewing by the Th2 cytokine, IL-4. SHIP protein levels are dramatically reduced when macrophages are skewed to an alternatively activate phenotype by IL-4 suggesting that increased PI3K activity may be required for canonical alternative activation of macrophages as well. We are currently characterizing the role of the PI3K pathway during canonical alternative activation of macrophages.Honours & AwardsThe G. Jeanette Thorbecke New Investigator Award from the Society for Leukocyte Biology (2012)
Canadian Association of Gastroenterology and Canadian Institutes of Health Research New Investigator Award (2009-2013)
Michael Smith Foundation for Health Research Scholar Award (2012-2021)
Research Group MembersNada Al-Emadi, Research Trainee
Chloe Bender-Thorsen, Masters Student
Rachel Dong, Directed Studies Student
Maggie Ma, Research Trainee
Sue Menzies, Research Assistant Technician
Yvonne Pang, PhD Candidate
Kwestan Safari, Grad Student
Teaching an old drug new tricks: How IVIg can help children with inflammatory bowel disease
A new BC Children’s Hospital study provides hope for children with Inflammatory Bowel Disease. Dr. Laura Sly is investigating how a drug approved 60 years ago could help kids today. The study shows that a drug made of pooled antibodies can reduce inflammation associated with ulcerative colitis.
