Professor and Head, Department of Immunology

Degrees:
M.Sc. (1972), Ph.D. (1977) (University of London, United Kingdom)

Mailing Address:
Department of Immunology
University of Manitoba
Faculty of Medicine
471 Apotex Centre
750 McDermot Avenue
Winnipeg, Manitoba
R3E 0T5

Phone: (204) 789-3509
Fax: (204) 789-3921
Email: moqbelr@cc.umanitoba.ca

Research Interests/Projects:

My research programme is focused on the following aspects of the immunobiology of the eosinophil and the potential contribution of this cell type to immune and inflammatory processes in allergy.

1. Intracellular mechanisms regulating leukocyte degranulation (exocytosis). The release of cytotoxic mediators stored in the large granules and small vesicles of inflammatory and immune cells plays a central role in many disease processes. Our studies on exocytosis are focused on eosinophils, as well as neutrophils, basophils and cytotoxic T-cells obtained from human blood. The aim is to identify targets for inhibition of granule and vesicle docking and exocytosis. We have identified VAMP-7, a member of the SNARE family of docking proteins, as a key player in regulating the intracellular mobilization and secretion of eosinophil granules and small secretory vesicles. These studies are currently being followed up in murine 'eosinophilic airway inflammatory models' to determine the precise role of eosinophil exocytosis and mediator secretions in allergic airway hyperresponsiveness and to determine the potential value of exocytosis associated proteins as effective therapeutic targets to downregulate local inflammatory responses.

2. Potential role of the eosinophil in regulating the adaptive development of immune bias towards the allergic-type response (known as Th2) while downregulating Th1-type responses. This study focuses on our novel observation that eosinophils constitutively express indoleamine 2,3-dioxygenase (IDO), which targets tryptophan for oxidative metabolism extrahepatically, thus resulting in a depletion of tryptophan and the generation of a complex family of biologically-active catabolites, known as kynurenines. The latter have been shown to target Th1 cells for apoptosis while allowing Th2 cell proliferation.

3. Identification and characterization of receptors for kynurenines on T helper cells potentially involved in immune modulation and tolerance.

4. Putative anti-tumour activity of human eosinophils, including oral squamous carcinomas where eosinophils may indicate positive prognosis. Our novel data show that eosinophils utilize pathways similar to cytotoxic T-cells and NK cells.

Highlighted Peer-Reviewed Publications

• Shaw RJ, Walsh GM, Cromwell O, Moqbel R, Spry CJF, Kay AB. 1985. Activated human eosinophils generate SRS-A leukotrienes following physiological (IgG-dependent) stimulation. Nature, (London) 316:150-152.

• Kay AB, Ying S, Varney V, Gaga M, Durham SR. Moqbel R, Wardlaw AJ, Hamid Q. 1991. Messenger RNA expression of the cytokine gene cluster, IL-3, IL-4, IL-5 and GM-CSF in allergen-induced late-phase cutaneous reactions in atopic subjects. Journal of Experimental Medicine, 173:775-778.

• Hamid Q, Azzawi M, Ying S, Moqbel R, Wardlaw AJ, Corrigan CJ, Bradley B, Durham SR, Collins JV, Jeffery PK, Quint DJ, Kay AB. 1991. Expression of mRNA for interleukin-5 in mucosal bronchial biopsies from asthma. Journal of Clinical Investigation, 87:1541-49.

• Moqbel R, Hamid Q, Ying S, Barkans J, Hartnell A, Tsicopoulos A, Wardlaw AJ, Kay AB. 1991. Expression of mRNA and immunoreactivity for the granulocyte/macrophage colony-stimulating factor (GM-CSF) in activated human eosinophils. Journal of Experimental Medicine, 174:749-752.

• Hamid Q, Barkans J, Abrams JS, Meng Q, Ying S, Kay AB., Moqbel R. 1992. Human eosinophils synthesize and secrete interleukin-6 in vitro. Blood, 80:1496-1501.

• Anwar ARE, Moqbel R, Walsh GM, Kay AB, Wardlaw AJ. 1993. Adhesion to fibronectin prolongs eosinophil survival. Journal of Experimental Medicine, 177:839-843.

• Jose PJ, Griffiths-Johnson DA, Collins PD, Walsh DT, Moqbel R., Totty NF, Truong O, Hsuan JJ, Williams TJ. 1994. Eotaxin: a potent eosinophil chemoattractant cytokine detectA?e?R?ed in a guinea pig model of allergic airways inflammation. Journal of Experimental Medicine, 179:881-887.

• Lacy P, Mahmudi-Azer S, Bablitz B, Hagen SC, Velazquez JR, Man SFP, Moqbel R. 1999. Rapid mobilization and release of intracellularly stored RANTES in response to interferon-g in human eosinophils. Blood, 94: 23-32.

• Lacy P, Logan MR, Bablitz B, Moqbel R. 2001. The fusion protein, vesicle-associated membrane protein-2 (VAMP-2) is implicated in interferon-g-induced piecemeal degranulation in human eosinophils from atopic individuals. Journal of Allergy and Clinical Immunology 107: 671-678.

• Logan MR, Lacy P, Bablitz B, Moqbel R. 2002. Expression of eosinophil target SNAREs as potential cognate receptors for vesicle-associated membrane protein-2 in exocytosis. Journal of Allergy and Clinical Immunology 109: 299-306.

• Mahmudi-Azer S, Downey GM, Moqbel R. 2002. Translocation of the tetraspanin CD63 in association with human eosinophil mediator release. Blood 99: 4039-4047.

• McNaughton L, Puttagunta L, Martinez-Cuesta MA, Kneteman N, Mayers I, Moqbel R, Hamid Q, Radomski MW. 2002. Distribution of nitric oxide synthase in normal and cirrhotic human liver. Proceedings of the National Academy of Science (PNAS), 99: 17161-17166.

• Lacy P, Abdel-Latif D, Steward M, MusatA?e?R?-Marcu S, Man SF, Moqbel R. 2003. Divergence of mechanisms regulating respiratory burst in blood and sputum eosinophils and neutrophils from atopic subjects. J Immunol;170(5):2670-9.

• Saude EJ, Lacy P, Musat-Marcu S, Mayes DC, Bagu J, Man SF, Sykes BD, Moqbel R. 2004. NMR analysis of neutrophil activation in sputum samples from patients with cystic fibrosis. Magn Reson Med;52(4):807-14.

• Odemuyiwa SO, Ghahary A, Li Y, Puttagunta L, Lee JE, Musat-Marcu S, Ghahary A, Moqbel R. 2004. Cutting edge: human eosinophils regulate T cell subset selection through indoleamine 2,3-dioxygenase. J Immunol;173(10):5909-13.

• Logan MR, Lacy P, Odemuyiwa SO, Steward M, Davoine F, Kita H, Moqbel R. 2006. A critical role for vesicle-associated membrane protein-7 in exocytosis from human eosinophils and neutrophils. Allergy;61(6):777-84.

• Marcet-Palacios M, Davoine F, Adamko DJ, Moqbel R, Befus AD. 2007. Human lymphocytes express the transcriptional regulator Wilms tumor 1; WT1 mediates nitric oxide-dependent repression of lymphocyte proliferation. Biochemical Biophysical Research Communications. 363:283-7.

• Marcet-Palacios M, Odemuyiwa SO, Coughlin J, Garofoli D, Ewen C, Davidson, C, Ghaffari M, Kane KP, Lacy P, Logan MR, Befus AD, Bleackley RC, Moqbel R. 2008. Vesicle-associated membrane protein 7 (VAMP-7) is essential for target cell killing in a natural killer cell line. Biochemical Biophysical Research Communications. 366:617-23.

• Adamko DJ, Wu Y, Ajamian F, Ilarraza R, Moqbel R, Gleich GJ. 2008. The Effect of Cationic charge on release of eosinophil mediators: role of surface receptors. Journal of Allergy and Clinical Immunology. 122:383-90.

• Davoine F, Min Cao, Wu Y, Ajamian F, Ilarraza R, Moqbel R, Adamko DJ. 2008. Virus-induced eosinophil mediator release: Antigen presentation to CD4+ T cells. Journal of Allergy and Clinical Immunology. 122:69-77.

• Coughlin JJ, Odemuyiwa SO, Davidson CE, Moqbel R. 2008. Differential expression and activation of Rab27A in human eosinophils: relationship to blood eosinophilia. Biochemical Biophysical Research Communications 373:382-6.

• Neves JS, Perez SAC, Spencer LA, Melo RCN, Reynolds L, Ghiran L, Mahmudi-Azer S, Odemuyiwa SO, Dvorak AM, Moqbel R*, Weller PF*. 2008. Eosinophil granules function extracellularly as receptor-mediated secretory organelles. Proceedings of the National Academy of Science, 105:18478-83. This study was initiated in my lab at the U of Alberta. *These two authors jointly supervised the study.

• Saude EJ, Obiefuna IP, Somorjai RL, Ajamian F, Skappak C, Ahmad T, Dolenko B, Sykes BD, Moqbel R, Adamko DJ. 2009. Metabolomic Biomarkers in a Model of Asthma Exacerbation: Urine Nuclear Magnetic Resonance. American Journal of Respiratory and Critical Care Medicine. 79:25-34.
• Odemuyiwa SO, Ebeling C, Duta V, Abel M, Puttagunta L, Cravetchi O, Majaesic C, Vliagoftis H, Moqbel R. 2009. Tryptophan Catabolites Regulate Mucosal Sensitization to Ovalbumin in Respiratory Airways. Allergy (In press)

Recent Editorials, Reviews, and Book Chapters

• Adamko D, Odemuyiwa SO, Moqbel R. 2003. The eosinophil as a therapeutic target in asthma: beginning of the end or end of the beginning? Curr Opin Pharmacol.3(3):227-32.

• Logan MR, Odemuyiwa SO, Moqbel R. 2003. Understanding exocytosis in immune and inflammatory cells: molecular basis of mediator secretion. Journal of Allergy and Clinical Immunology 111: 923-932.

• Adamko DJ, Lacy P, Moqbel R. 2004. Eosinophil Function in Allergic Inflammation: From Bone Marrow to Tissue Response. Current Allergy and Asthma Reports, 4:149-58.

• Adamko DJ, Odemuyiwa SO, Vethanayagam D, Moqbel R. 2005. The rise of the Phoenix: The expanding role of the eosinophil in health and disease. Allergy. 60(1):13-22.

• Moqbel R, Coughlin JJ. 2006. Differential secretion of cytokines. Sci STKE;2006(338):pe26.

• Hogan SP, Rosenberg HF, Moqbel R, Phipps S, Foster PS, Lacy P, Kay AB, Rothenberg ME. 2008. Eosinophils: biological properties and role in health and disease. Clin Exp Allergy 38:709-50.

• Moqbel R, Lacy, P, Adamko DJ, Odemuyiwa SO. 2008. Biology of Eosinophils. In: Middleton's Allergy: Principles & Practice, 7th Edition. Editor(s): F Adkinson, BF Bochner, WW Busse, ST Holgate, R Lemanske, & ESE Simons. Mosby Elsevier Publishers. Volume 1, Chapter 18. 295-310.

• Hogan SP, Rosenberg HF, Moqbel R, Phipps S, Foster PS, Lacy P, Kay AB, Rothenberg ME. 2008. Eosinophils: Biological properties and role in health and disease. In Allergy and Allergic Diseases; Second Edition. Editors: A.B. Kay, Jean Bousquet, Patrick G. Holt, Allen P. Kaplan. Wiley Publishing. Volume 1.

• Moqbel R, Lacy P, Odemuyiwa SO, Adamko DJ. 2009. The Human Eosinophil. In: Wintrobe's Clinical Hematology, 12th Edition. JP Greer, J Foerster, JN Lukens, GM Rogers, F Paraskevas, & B Glader, Editors; Lippincott Williams & Wilkins. Volume 1; Part 2, Section 3, Chapter: 10; 214-235.

• Moqbel R. and Odemuyiwa SO. 2009. Allergy, Asthma and Inflammation: Which Inflammatory Cell-type is More Important? Allergy, Asthma and Clinical Immunology (In press).

Current Sources of Funding

• CIHR Operating grant (2008-2013): Intracellular Mechanisms Regulating Eosinophil Exocytosis; $172,772.00 p.a.
• CIHR Operating grant (2004-2009): Potential Role of Eosinophils in T-Cell Regulation Through Indoleamine 2,3-dioxygenase (IDO); $101,000.00 p.a.
• AHFMR Research Prize (2002-2007): $40,000.00
• AllerGen NCE (2005-2008): Tryptophan metabolltes and glutamate receptors in the pathogenesis and therapy of allergic disease; $125,000 p.a.
• AllerGen-NCE (Co-PI, 2005-2008): Urine NMR in asthma; $100,000 p.a.

Current Laboratory Members:

University of Alberta
Dr. Saswati Das	Research Associate (based at the University of Alberta)
Cory Ebeling, PhD (University of Alberta, with Dr. Darryl Adamko)	Post Doctoral Fellow
Olga Cravetchi, MD (University of Alberta)	Graduate Student
Farnam Ajamian, MD (University of Alberta with Dr Darryl Adamko)	Graduate Student
John Dongil Kim, BSc	Graduate Student (University of Alberta with Dr. Paige Lacy)
Lian Willets, BSc	Graduate Student (University of Alberta with Dr. Paige Lacy)
University of Manitoba
Dr. Narcy Arizmendi Puga	Research Associate
Dr. Kanami Orihara, Ph.D.	Post Doctoral Fellow
Dr. Ramses Ilarazza	Post Doctoral Fellow
Vidyanand (Nandu) Anaparti	Graduate Student (Ph.D. Program)
Sonia Charran	Graduate Student (M.Sc. Program)

Former Research Personnel:

Research Associate SO (Wole) Odemuyiwa, DVM, MSc, PhD (Residency program in Veterineary Pathology, Guelph University)	Technicians Yanling Feng, MD Courtney Davidson
Former Research Trainees
Valentin Duta, PhD MD Medical Resident, Capital Health, Edmonton	Salahaddin Mahmudi-Azer, PhD
Jason Coughlin, PhD, Medical student, University of Alberta	Michael R Logan, PhD Post-doctoral Fellow McGill University
Sorin Musat-Marcu, MD, PhD President, HistoBest Inc.	Francis Davoine, PhD Sessional Assistant Professor Campus Saint-Jean, University of Alberta
Michael R Logan, PhD Post-doctoral Fellow University of Alberta	Angela Haczku, PhD Associate Professor of Medicine University of Pennsylvania Medical Center, Pulmonary & Critical Care Division, Abramson Research Center
Joo Eun Lee, MSc PhD candidate University of Toronto	Matthew Wakelin, PhD Scientific Officer Medical Research Council United Kingdom
Rusanna Dyatlova, MD, MSc Medical Resident	Keith E Zukiwski, MSc Chartered Psychologist Integrative Medicine Institute Calgary, Alberta
Negar Asdaghi, MD, MSc Medical Resident University of Alberta	Daniella Garofoli, MSc MBA Student University of Manitoba
Angus MacDonald, PhD	Juan Velazquez, PhD
Paige Lacy, PhD Assistant Professor Division of Pulmonary Medicine, Department of Medicine Faculty of Medicine and Dentistry University of Alberta	Andreas Schwingshackl, PhD Pediatric Critical Care Physician Department of Pediatrics Mattel Childrens Hospital University of California at Los Angeles United States of America
Harissios Vliagoftis, MD Associate Professor Division of Pulmonary Medicine Department of Medicine, University of Alberta