Dr. Darryl A. Knight, Ph.D.
Canada Research Chair in Airway Disease
|Department of Anesthesiology, Pharmacology and Therapeutics|
Dr. Knight obtained his PhD at the University of Western Australia in 1993 and did post doctoral training at the University of British Columbia. From 1997 to 2001 he was a Senior Research Officer in the Asthma & Allergy Research Institute of the University of Western Australia and was Head of the Experimental Biology division of the Institute from 2002-2004. He was also an Adjunct Senior Lecturer in the Department of Medicine at the University of Western Australia.
Dr. Knight’s research program consists of complementary projects centered on understanding how the respiratory system repairs itself after inflammatory insult and why in susceptible asthmatics, inflammation results in ongoing and abnormal remodeling rather than a self-limited healing process. The particular focus of this program is the epithelial cell and fibroblast in modulating the repair process.
The current objectives of Dr. Knight’s research program are centred on investigating the mechanisms of airway epithelial repair following damage induced by a variety of stimuli focusing on 3 key objectives: (1) Characterize the phenotype of epithelial-resident progenitor cells involved in repair in human airways (2) Determine whether bone marrow derived progenitor cells play a role in epithelial repair, and if so, what is the relative contribution of these cells to tissue resident progenitor cells under normal conditions and in the presence of underlying allergic disease (3) Examine whether airway progenitor cells have potential for both epithelial and mesenchymal differentiation.
Dr. Knight is also actively investigating the role of the IL-6/gp130 in the pathogenesis of pulmonary fibrosis. The specific goal of this project is to identify novel molecular mechanisms for the treatment, diagnosis and prognosis of IPF focusing on our insights that cytokines that signal through gp130 may be critical determinants of disease susceptibility and progression. gp 130 is a shared component in the receptor complexes for the IL-6 family of cytokines that also includes IL-11, Leukemia Inhibitory Factor (LIF) and Oncostatin M (OSM) which are important regulators of both the phenotype and proliferation of fibroblasts in health and in response to injury.
(all references are linked on PubMed)
Moodley YP, Rigby PJ, Blundell C, Bunt S, Hayashi H, Misso NLA, McANULTY RJ, Scaffidi AK, Laurent GJ, Thompson PJ, Knight DA. Macrophage recognition and phagocytosis of apoptotic fibroblasts is critically dependent on fibroblast-derived thrombospondin-1 and CD36. American Journal of Pathology, 2003,162: 771-779.
Knight DA, Holgate ST. The biology of the epithelial cell in health and disease. Respirology, 2003; 8:432-446.
Moodley YP, Scaffidi AK, Misso NLA, Keerthisingam C, McAnulty RJ, Laurent GJ, Mutsaers SE, Thompson PJ, Knight DA. Fibroblasts isolated from normal lungs and those with idiopathic pulmonary fibrosis differ in IL-6/gp130-mediated cell signaling and proliferation. American Journal of Pathology, 2003, 163: 345-353.
Moodley YP, Misso NLA, Scaffidi AK, Fogel-Petrovic M, McAnulty RJ, Laurent GJ, Thompson PJ, Knight DA. Inverse effects of IL-6 on apoptosis of fibroblasts from pulmonary fibrosis and normal lungs. American Journal of Respiratory Cell and Molecular Biology, 2003, 29: 490-498.
Knight DA, Ernst M, Anderson GP, Moodley YP, Mutsaers SE. IL-6 cytokines and the development of pulmonary fibrosis. Pharmacology and Therapeutics, 2003; 99: 327-333.
Moodley YP, Caterina PM, Papadimitriou JM, Misso NLA, McAnulty RJ, Laurent GJ, Thompson PJ, Knight DA. Overlapping ultrastructural, morphological and biochemical processes between fibroblasts from normal lungs and those from cryptogenic fibrosing alveolitis. Journal of Pathology, 2004, 202: 486-495.
Knight DA, Lane CL, Stick SM. Does aberrant activation of the epithelial mesenchymal trophic unit play a key role in asthma or is it an unimportant sideshow? Current Opinion in Pharmacology 2004; 4: 251-256
Scaffidi AK, Petrovic N, Moodley YP, Fogel-Petrovic M, Kroeger KM, Seeber RM, Eidne KA, Thompson PJ, Knight DA. alpha(v)beta(3) Integrin interacts with the transforming growth factor beta (TGFbeta) type II receptor to potentiate the proliferative effects of TGFbeta1 in living human lung fibroblasts. J Biol Chem. 2004;279:37726-37733.
Bai TR, Knight DA. Structural changes in the airways in asthma: observations and consequences. Clin Sci (Lond). 2005;108:463-477.
Lane CS, Burgess S, Kicic A, Knight DA, Stick SM. The use of non-bronchoscopic brushings to study the paediatric airway. Respir Res. 2005;6:53.
Weichselbaum M, Sparrow MP, Hamilton EJ, Thompson PJ, Knight DA. A confocal microscopic study of solitary pulmonary neuroendocrine cells in human airway epithelium. Respir Res. 2005;6(1):115.