Dr. David Walker is an Associate Professor Emeritus in the Department of Pathology and Laboratory Medicine at the University of British Columbia. He has earned Bachelors degrees in both Zoology (1968) and Botany (1970) from the University of California at Santa Barbara , followed by a Masters degree in Botany (1972).
He completed a PhD in Botany at the University of British Columbia in 1980 after having begun as a Research Assistant in the Pulmonary Research Laboratory in February 1979. In 1983 he was appointed as an Assistant Professor in the Department of Pathology and Laboratory Medicine at UBC. He was promoted to Associate Professor in 1996.
Pulmonary Research Laboratory and University Commitments:
Dr. Walker supervised the Electron Microscopy Laboratory of the Pulmonary Research Laboratory at St. Paul’s Hospital for 22 years. He is currently co-director of core 2 of the iCAPTURE Centre. He annually contributes two lectures to PATH 520 (Pulmonary Cell Biology) and gives a lecture in PATH 518 (Pulmonary Pathophysiology). He served as Graduate Advisor for the Department of Pathology and Laboratory Medicine at University of British Columbia from 2003 to 2010.
In the Department of Pathology and Laboratory Medicine at UBC, Dr. Walker is a member of the Bachelor or Medical Laboratory Science Committee, and the teaching assessment committee. He was a member of the Graduate Studies Committee for two terms. He has chaired two MSc and six PhD committees for the Department of Pathology. He has been a regular committee member of nine MSc and two PhD committees. He has supervised two MSc students, one jointly with Dr. Joel Bert of Chemical Engineering at UBC. This commitment continues into the students PhD program. He has also served as a university examiner on two PhD thesis defenses. He is currently a member of three PhD committees.
Dr. Walker co-coordinates PATH 305 (Modern Microscopy) in the BMLSc Program; he was the sole coordinator up until 1994. In February 1999 he tutored the five-week Pulmonary Block in the Problem Based Learning curriculum for the Faculty of Medicine and then the first Basic Science Block in September 1999. In 2000 he was made week Captain of week four in that block and ran it for the last four years.
- PhD, University of British Columbia, Botany. 1980
- MA, University of California, Santa Barbara, Botany. 1972
- BA, University of California, Santa Barbara, Botany. 1970
- BA, University of California, Santa Barbara, Zoology. 1968
- Borok Z, Whitsett JA, Bitterman PB, Thannickal VJ, Kotton DN, Reynolds SD,
Krasnow MA, Bianchi DW, Morrisey EE, Hogan BL, Kurie JM, Walker DC, Radisky DC, Nishimura SL, Violette SM, Noble PW, Shapiro SD, Blaisdell CJ, Chapman HA; other participants. Cell Plasticity in Lung Injury and Repair: Report from an NHLBI
Workshop, April 19-20, 2010. Proc Am Thorac Soc. 2011 Jun;8(3):215-22.
- Tranfield EM, van Eeden SF, Yatera K, Hogg JC, Walker DC. Ultrastructural changes in atherosclerotic plaques following the instillation of airborne particulate matter into the lungs of rabbits. Can J Cardiol. 2010 Jul;26(7):e258-69.
- Behzad AR, Walker DC, Abraham T, McDonough J, Mahmudi-Azer S, Chu F, Shaheen F, Hogg JC, Paré PD. Localization of DNA and RNA in eosinophil secretory granules. Int Arch Allergy Immunol. 2010;152(1):12-27.
- Behzad AR, McDonough JE, Seyednejad N, Hogg JC, Walker DC. The disruption of the epithelial mesenchymal trophic unit in COPD. COPD. 2009 Dec;6(6):421-31.
- Monsalve MV, Humphrey E, Walker DC, Cheung C, Vogl W, Nimmo M. Brief communication: state of preservation of tissues from ancient human remains found in a glacier in Canada. Am J Phys Anthropol. 2008 Nov;137(3):348-55.
- Matsukura M, Chu FF, Au M, Lu H, Chen J, Rietkerk S, Barrios R, Farley JD, Montaner JS, Montessori VC, Walker DC, Côté HC. Liver ultrastructural morphology and mitochondrial DNA levels in HIV/hepatitis C virus coinfection: no evidence of mitochondrial damage with highly active antiretroviral therapy. AIDS. 2008 Jun 19;22(10):1226-9.
- Scott A, Cook JL, Hart DA, Walker DC, Duronio V, Khan KM. Tenocyte responses to mechanical loading in vivo: a role for local insulin-like growth factor 1 signaling in early tendinosis in rats. Arthritis Rheum. 2007 Mar;56(3):871-81.
- Sirianni FE, Milaninezhad A, Chu FS, Walker DC. Alteration of fibroblast architecture and loss of Basal lamina apertures in human emphysematous lung. Am J Respir Crit Care Med. 2006 Mar 15;173(6):632-8.
- Choy JC, Podor TJ, Yanagawa B, Lai JC, Granville DJ, Walker DC, McManus BM. The regulation and consequences of immune-mediated cell death in atheromatous diseases. Cardiovasc Toxicol. 2003;3(3):269-82. Review.
- Dr. Walker has published 44 peer-reviewed articles and 62 abstracts. For the past 10 years the focus of Dr. Walker’s research has been the process of white blood cell migration in the lungs. In the course of this work he has identified and described a novel avenue for the trafficking of both molecules and white blood cells across the blood vessel walls of the lungs at tricellular corners in the endothelium. He has demonstrated a pathway from both capillaries of the alveoli and postcapillary venules of conducting airways to the respective airways along which white blood cells appear to migrate. This pathway is characterized by fibroblasts that singly in the alveolar walls and as a reticulum in the conducting airway walls provide a substrate along which white blood cells may crawl from holes in the vascular basal laminae to holes in the epithelial basal laminae.This is a completely novel observation and may transform how the process of leukocyte migration is both viewed and how it is mediated. He has developed experimental models for both neutrophilic and eosinophilic white blood cell migration that are relevant to pneumonias, cystic fibrosis, allergic inflammation and parasitic inflammatory responses. Furthermore, while Dr. Walker’s emphasis has been on in vivo studies he has developed collaborative studies using in vitro models of leukocyte migration with Dr. C. Wayne Smith of Baylor at Houston and models for the study of fibroblast/fibroblast and fibroblast/extracellular matrix mechanical connections with Dr. Joel Bert of Chemical Engineering at UBC. Most recently we have established the existence of the pathway for leukocyte migrations in the human lung and demonstated how it is disrupted in emphysematous human lung.
- As a youngster, and as a biologist and a cell biologist, I have always been enchanted with the relationship between structure and function. Because of the unique architecture and function of the lung with its unusual vascular systems, inflammatory processes affecting it are also unique and not directly comparable to those in other organ systems. I began my studies of inflammation in the airways in the Pulmonary Research Laboratory with Prof. James Hogg using light and transmission electron microscopy. These studies were focused on central airway inflammation in response to tobacco smoke insults. These studies focused on the epithelial barrier as it relates to alterations in permeability and inflammatory cell traffic. We ultimately determined that significant changes in permeability were occurring in the peripheral lung just distal to the bronchioloalveolar junctions , not in the central airways .
Since then my recent work has been focused on inflammation in the peripheral lung. Because the alveoli are in simplest terms an epithelial surface layer juxtaposed to an endothelial surface, I have incorporated freeze-fracture and scanning electron microscopy into my research efforts because of the resolving power gained to visualize biological surfaces and assess barrier function of both endothelial and epithelial structure and function. Using perfused microspheres and scanning electron microscopy in rabbit and guinea pig lungs, I have determined how to differentiate arteriolar from venular endothelium in the lungs. Using freeze-fracture, I have demonstrated the morphological distinctness of endothelial tight junctions as compared to epithelial tight junctions and defined for the first time the organization of the tricellular region of endothelial tight junctions. This and an earlier work of mine taken together demonstrated that neither epithelial nor endothelial tight junctions make a continuous belt around the cell. These observations drive a qualitative shift in our understanding of the functions and development of epithelial and endothelial tight junctions. We have already begun to sort out the consequences of these data to our understanding of how migrating white blood cells emigrate from the vasculature. I have demonstrated that many white blood cells diapedies across the endothelium at tricellular junctions (where three cells meet). Our new interpretation of tricellular tight junction organization makes it possible to explain how migrating white cells can cross these layers during an inflammatory reaction without disrupting the tight junctions themselves. My curiosity has led me beyond diapedesis. I began with Streptococcal pneumonia which is a non-necrotizing pneumonia. I have developed and am testing a working hypothesis that explains why the inflammatory reaction in a non-necrotizing pneumonia does not result in permanent lung damage and scarring. To do this we have used a Streptococcal pneumonia rabbit model and a combination of morphometric analysis and serial sectioning. We have now demonstrated that neutrophils do not disrupt alveolar wall architecture in order to migrate by the secretion of lysosomal enzymes, but rather they pass through pre-existing holes in the basal laminae of both endothelium and epithelium. Furthermore, we have made preliminary observations suggesting how pulmonary fibroblasts might guide neutrophils from capillaries to type 2 pneumocytes where they have been shown by others to emerge into the alveoli. We are currently investigating the molecular mechanisms that might make this possible by using cryoultramicrotomy and colloidal gold immunocytochemistry. As a biological control for this phenomena we are also doing parallel studies on Pseudomonas aeruginosa pneumonia in rabbit and just recently have made observations that may explain how such a pneumonia differs from a non-necrotizing pneumonia and why.
The further I delve in my investigation of the mechanisms whereby neutrophils make their way through tissues during an inflammatory response it becomes clear that the investigation of these tissues and their components will need to proceed with the likes of the atomic force microscope. This miraculous instrument permits one to observe the surfaces of live biological specimens and their constituents in an aqueous environment in real time and at greater than transmission electron microscopic resolution. I have begun to explore the basal lamina of the rabbit trachea with people from Digital Instruments who make and market an atomic force microscope. We have images that show differences in extracellular elements with directional stretch. This new technique is the new horizon in the imaging and investigation of biological systems at the molecular and atomic levels of organization.
- September 1997: Began a collaborative study of the organization of fibroblasts in skin and the effect of their interconnections on the mechanical characteristics of that tissue with Dr. Joel Bert of the Department of Chemical Engineering. I am supervising the morphological assessment of fibroblast integrity in control and treated skin samples being done by his graduate student.
- September 1997: Collaborative study with Drs. Alan Burns and C. Wayne Smith of Baylor School of Medicine in Houston was published in J. Immunology 159:2893-2903, 1997, in which we demonstrated that neutrophils preferentially diapedese at tricellular corners in Human Umbilical Vein Endothelial Cell cultures.