Dawn Bowdish

, PhD

Assistant Professor
Pathology and Molecular Medicine

Division: Molecular Medicine

4020 Michael DeGroote Centre for Learning & Discovery
Tel: 905-525-9140 ext 22313
Lab: MDCL-4077 ext 21551
bowdish@mcmaster.ca

Bowdish Lab Website

Assistant: Michelle Allan

Currently accepting applications from graduate students and post-docs

Education and Professional Standing

PDF. University of Oxford, 2008
PhD. University of British Columbia, 2005
BSc. University of Guelph, 2000

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Interests

Research Focus

Macrophages are the sentinel cells of the immune response; their role is to detect pathogens via expression of surface receptors. Generally they are effective in clearing the pathogen without mounting an inflammatory response; however, when a pathogen evades detection or clearance, they are instrumental in mobilizing an appropriate immune response. In some cases a frustrated attempt to resolve infection or an inappropriate response to non-infectious stimuli can result in tissue damage and sterile inflammation. Because macrophage receptors are crucial to this initial interaction to pathogens and shape the downstream immune response, factors that alter the rate or magnitude of receptor expression (e.g. slight genetic variations in receptor genes) can have profound effects on an individual’s susceptibility to infection.

Research interests in the Bowdish lab include:

• The role of the macrophage scavenger receptors in host defence.

The two major class A scavenger receptors are called SRA and MARCO, which have high levels of homology but sharply opposing patterns of regulation. SRA is constitutively expressed on macrophages whereas MARCO expression is inducible and is upregulated in response to toll like receptor agonists. The primary role of SRA appears to be clearance of modified host proteins and lipids while MARCO is associated with the response to infectious disease. Mice defective in expression of either MARCO or SRA are immunocompromised in multiple models of infection. Ongoing work is being performed to determine the role of these receptors in binding, recognition and signalling in response to bacterial components and recruitment and motility of leukocytes.

• Understanding how subtle genetic variation in macrophage receptor genes alters the host’s response to infection.

Genetic studies have identified that SNPs in macrophage receptors are associated with an individual’s susceptibility to infectious disease; however, elucidating the functional significance of these observations has proven difficult. By using bioinformatics and molecular biology approaches I have been able to identify SNPs that are associated with alterations of scavenger receptor expression & function.

• Using macrophage receptors as markers of immunomodulation.

Macrophage receptor expression is dynamic and depends on factors in the local environment (e.g. the cytokine milieu, cell-cell interactions, exposure to pathogen associated molecular patterns). Characteristic patterns of macrophage receptor expression are indicative of functional properties of those cells (e.g. the capacity to kill intracellular pathogens). Thus, macrophage markers are important indicators of the local immune environment and manipulation of expression is useful in design of adjuvants and immunomodulatory agents.

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Team Members

Undergraduate Students: Zhonyuan Tu, Alex Jiang, Harikesh Wong

Graduate Students: Dawn Ashforth

Selected Publications

• Bowdish DME, Sakamoto K, Kim MJ, Kroos M, Mukhopadhyay S, Leifer CA, Tryggvason K, Gordon S, Russell DG. MARCO, TLR2, and CD14 are required for macrophage cytokine responses to mycobacterial trehalose dimycolate and Mycobacterium tuberculosis. PLoS Pathog. 2009 Jun;5(6):e1000474.
• Bowdish DME, Gordon S. Conserved domains of the class A scavenger receptors: evolution and function. Immunol Rev. 2009 Jan;227(1):19-31.
• Yu J, Mookherjee N, Wee K, Bowdish DME, Pistolic J, Li Y, Rehaume L, Hancock REW. Host defense peptide LL-37, in synergy with inflammatory mediator IL-1beta, augments immune responses by multiple pathways. J Immunol. 2007 Dec 1;179(11):7684-91.
• Bowdish DME, Loffredo MS, Mukhopadhyay S, Mantovani A, Gordon S.Macrophage receptors implicated in the "adaptive" form of innate immunity. Microbes Infect. 2007 Nov-Dec;9(14-15):1680-7.
• Chang GW, Davies JQ, Stacey M, Yona S, Bowdish DME, Hamann J, Chen TC, Lin CY, Gordon S, Lin HH. CD312, the human adhesion-GPCR EMR2, is differentially expressed during differentiation, maturation, and activation of myeloid cells. Biochem Biophys Res Commun. 2007 Feb 2;353(1):133-8.
• Davidson DJ, Currie AJ, Bowdish DME, Brown KL, Rosenberger CM, Ma RC, Bylund J, Campsall PA, Puel A, Picard C, Casanova JL, Turvey SE, Hancock REW, Devon RS, Speert DP. IRAK-4 mutation (Q293X): rapid detection and characterization of defective post-transcriptional TLR/IL-1R responses in human myeloid and non-myeloid cells. J Immunol. 2006 Dec 1;177(11):8202-11.
• Bowdish DME, Davidson DJ, Hancock REW. Immunomodulatory properties of defensins and cathelicidins. Curr Top Microbiol Immunol. 2006;306:27-66.
• Barlow PG, Li Y, Wilkinson TS, Bowdish DME, Lau YE, Cosseau C, Haslett C, Simpson AJ, Hancock REW, Davidson DJ. The human cationic host defense peptide LL-37 mediates contrasting effects on apoptotic pathways in different primary cells of the innate immune system. J Leukoc Biol. 2006 Sep;80(3):509-20.
• Gibbons MA, Bowdish DME, Davidson DJ, Sallenave JM, Simpson AJ. Endogenous pulmonary antibiotics. Scott Med J. 2006 May;51(2):37-42.
• Mookherjee N, Brown KL, Bowdish DME, Doria S, Falsafi R, Hokamp K, Roche FM, Mu R, Doho GH, Pistolic J, Powers JP, Bryan J, Brinkman FS, Hancock REW. Modulation of the TLR-mediated inflammatory response by the endogenous human host defense peptide LL-37. J Immunol. 2006 Feb 15;176(4):2455-64.
• Lau YE, Bowdish DME, Cosseau C, Hancock REW, Davidson DJ. Apoptosis of airway epithelial cells: human serum sensitive induction by the cathelicidin LL-37.Am J Respir Cell Mol Biol. 2006 Apr;34(4):399-409.
• Bowdish DME, Hancock REW. Anti-endotoxin properties of cationic host defence peptides and proteins. J Endotoxin Res. 2005;11(4):230-6. Review.
• Bowdish DME, Davidson DJ, Scott MG, Hancock REW.. Immunomodulatory activities of small host defense peptides. Antimicrob Agents Chemother. 2005 May;49(5):1727-32.
• Bowdish DME, Davidson DJ, Hancock REW. A re-evaluation of the role of host defence peptides in mammalian immunity. Curr Protein Pept Sci. 2005 Feb;6(1):35-51.
• Bowdish DME, Davidson DJ, Lau YE, Lee K, Scott MG, Hancock REW. Impact of LL-37 on anti-infective immunity. J Leukoc Biol. 2005 Apr;77(4):451-9. E
• Bowdish DME, Davidson DJ, Speert DP, Hancock REW. The human cationic peptide LL-37 induces activation of the extracellular signal-regulated kinase and p38 kinase pathways in primary human monocytes. J Immunol. 2004 Mar 15;172(6):3758-65.
• Davidson DJ, Currie AJ, Reid GS, Bowdish DME, MacDonald KL, Ma RC, Hancock REW, Speert DP. The cationic antimicrobial peptide LL-37 modulates dendritic cell differentiation and dendritic cell-induced T cell polarization. J Immunol. 2004 Jan 15;172(2):1146-56.
• Scott MG, Davidson DJ, Gold MR, Bowdish DME, Hancock REW. The human antimicrobial peptide LL-37 is a multifunctional modulator of innate immune responses. J Immunol. 2002 Oct 1;169(7):3883-91.