CURRICULUM VITAE

DR. MICHAEL J.H. RATCLIFFE

Name: Michael John Hayward Ratcliffe

Office address: Department of Immunology, University of , Medical Sciences Building, 1 King’s College Circle, Toronto, , Canada M5S 1A8

Lab address Sunnybrook Health Sciences Center, 2075 Bayview Avenue, Room A3-31, Toronto, Ontario, Canada, M4N 3M5

Tel (office): (416)-978 6382 Tel (lab): (416)-480 6103 Fax: (416)-978 1938

e.mail: [email protected]

Date of Birth: August 8, 1954 Nationality: Dual national: British/Canadian Marital status: Married, two children (born 1988 and 1990)

A. Date of CV preparation January 2010

B. Biographical information

1. Degrees: Ph.D. 1980. University College London, England. Immunology. B.Sc. 1976. The University of Glasgow, Glasgow, Scotland. Honours Biochemistry.

2. Employment:

2001-present Professor and Chair, Department of Immunology, , Toronto, Ontario, Canada.

1 2001-present Senior Scientist, Discipline of Molecular and Cell Biology, Sunnybrook Health Sciences Center, Toronto, Ontario, Canada. 2001-present Full Member, School of Graduate Studies, University of Toronto. 2009-present Member of Senate, Trinity College, University of Toronto. 2007-present Fellow, Trinity College, University of Toronto. 2003-2007 Associate Fellow, Trinity College, University of Toronto. 2005-2006 Interim Discipline Director, Molecular and Cell Biology, Sunnybrook Health Sciences Center, Toronto, Ontario, Canada. 1998-2001 Professor, Department of Microbiology and Immunology, McGill University, Montreal, , Canada. 1991-1998 Associate Professor, Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada. 1991 Tenure awarded, McGill University. 1986-1991 Assistant Professor, Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada. 1983-1986 I.C.R.F. Research Fellow, Imperial Cancer Research Fund, Tumour Immunology Unit, University College London, London, U.K. 1980-1983 Member, Basel Institute for Immunology, Basel, Switzerland.

3. Honours

1993-1996 Fonds de la Recherche en Santé du Québec Chercheur-boursier (Senior 2). 1990-1993 Fonds de la Recherche en Santé du Québec Chercheur-boursier (Senior 1). 1987-1990 Fonds de la Recherche en Santé du Québec Chercheur-boursier (Junior 2). 1983-1986 Imperial Cancer Research Fund Research Fellowship. 1976-1980 Wellcome studentship.

4. Professional affiliations and activities:

4.1 Societies

British Society for Immunology: 1978-present Member.

2 Canadian Society for Immunology: 1988-present Member, 1991-1993 Member of council. 1993-1995 Re-elected to council. 1999-2001 Vice-President. 2001-2003 President. 2003-2005 Past-President. 2008-present Outreach councilor.

Canadian Federation of Biological Societies: 1999-2003 Member of Executive Council. 2004-2005 President-Elect. 2005-2007 President. 2007-2009 Past President.

American Association of Immunologists: 2001-present Member.

International Union of Immunology Societies: 1991-2001 Chair: Avian CD Nomenclature Committee. 2001-2010 Member: General Assembly (one of two Canadian members).

4.2 Grant review:

Panel membership: 1989-1991 Member: FRSQ panel for graduate studentships (M.Sc. level). 1991-1993 Member: Cancer Research Society Fellowships Committee. 1993-1996 Member: MRC Immunology and Transplantation Operating grants panel. 1996-1999 Scientific Officer: MRC Immunology and Transplantation Operating grants panel. 2000-2003 Chairman: CIHR (formerly MRC) Immunology and Transplantation Operating Grants Panel. 2003-2004 Invited member: CIHR Multi-User Equipment and Maintenance grant panel. 2004-2005 Member: CIHR Multi-User Equipment and Maintenance grant panel. 2004 Member: Ontario College of Graduate Studies; site visit reviewer for Department of Microbiology and Immunology, University of Western Ontario. 2004-present Member: College of Reviewers, Canada Research Chairs.

3 2005-2006 Invited Chair: CIHR Immunology and Transplantation Operating grants panel. 2006-2009 Chairman: CIHR Immunology and Transplantation Operating grants panel B. 2006-2008 Member: Ontario Research Fund: Research Excellence Committee. 2007-2009 Member: Canada Research Chairs Interdisciplinary Adjudicating Committee. 2007 Member: International Review Committee for the Institut de recherches cliniques de Montréal. 2009 Member: CIHR Strategic Training Program Grant panel B.

Ad hoc reviewer: Fonds de la Recherche en Santé du Québec Medical Research Council of Canada Natural Sciences and Engineering Research Council of Canada National Cancer Institute of Canada Canadian Institutes of Health Research Saskatchewan Health Research Foundation British Columbia Health, Michael Smith Health Research Alberta Heritage Unites States Department of Agriculture National Institutes of Health, USA National Science Foundation, USA Science Foundation Ireland

4.3 Editorial boards

Guest editor: Seminars in Immunology, volume 2 issue 3, 1990. B Lymphocyte Development. Saunders Scientific Publications. International Editorial Advisory Board: Veterinary Immunology and Immuno- pathology, 1999-present. Editorial Advisory Board: Seminars in Immunology 2001-present. Editor-in-Chief: Encyclopedia of Immunology 3rd Edition. Elsevier;. 5 volumes, 3750 pages. Publication targeted 2011.

Ad hoc reviewer: Canadian Journal of Allergy and Clinical Immunology, Cellular Immunology, Development and Comparative Immunology, Developmental Dynamics, European Journal of Immunology, Experimental Molecular Pathology, Immunobiology, Immunology, Immunological Investigations, Immunology Letters, International Immunology, Journal of Anatomy, Journal of Clinical Immunology, Journal of Experimental Medicine, Journal of Immunology, Journal of Leukocyte

4 Biology, Journal of Molecular Medicine, Nature, Oncogene, Trends in Immunology, Veterinary Research, Veterinary Immunology and Immunopathology.

4.4 Consultancies

Moore and Van Allen Pllc., Attorneys at Law (Durham, North Carolina); Expert witness reports and testimony in patent litigation, 1997-1998. Member: Scientific Advisory Board: Origen Therapeutics (Burlinghame, CA, USA), 2000-present.

4.5 University committees

4.5.1 Departmental (1986-2001, McGill University; 2001-present, University of Toronto)

Immunology Promotions and Appointments Committee (2001-present) Immunology Undergraduate Committee (2001-present) Immunology Graduate Committee (2001-present) Immunology Faculty Search Committees (2001-present) Microbiology and Immunology Animal Care Committee (member 1986- 1994, Chair 1994-2001). Microbiology and Immunology Undergraduate Committee (member 1989-2001). Microbiology and Immunology Graduate Committee (member 1993- 2001) Microbiology and Immunology Curriculum Review Committee (member 1995-1996). Microbiology and Immunology Seminar Committee (member 1987-1989, chair 1989-1994, member 1998-1999).

4.5.2 Faculty and University (1989-2001, McGill University; 2001-present, University of Toronto)

University of Toronto Transplantation Institute Executive Committee (member, 2009-present). University of Toronto Bacardi Chair in Transplantation search committee (member, 2009-present). Dean of Medicine’s Advisory Committee on International Research (2009- present).

5 Ontario Cancer Institute Search Committee for Clinician Scientist in Immunotherapy (member, 2009-present) Dean of Medicine’s Advisory Committee on Space Planning, (member, 2008-present). Dean of Medicine’s Search Committee for Chair of Medical Biophysics (member, 2007-2008). Dean of Medicine’s Task Force on Faculty Data (member, 2004-2005). Medical Student Research Day (poster judge, 2003-present). Regenerative Medicine Executive Committee (member, 2002-present). Life Science Planning Curriculum Committee (member, 2002-present). Dean of Medicine’s Task Force on Undergraduate Medical Education (member 2001-2002). Dean of Medicine’s Task Force on Basic Medical Science Teaching in Arts and Science (member 2001-2002). Dean of Medicine`s Task Force on promotion and tenure (member 2001- 2001). University of Toronto Blue Sky Canada Research Chair in Women’s Health Search Committee (member, 2004-2006). Regenerative Medicine Training Program Executive Committee (member, 2002-present). University of Toronto Multi-Organ Transplant Executive Committee (member, 2001-2009).

McGill University Faculty of Medicine Interdepartmental Flow Cytometry Facility (Director, 1994-2001). Lyman Duff Building Interdepartmental Animal Facility (Director, 1997- 2001). Dean of Medicine’s Advisory Committee on Canada Research Chairs (2000-2001). Dean of Medicine's Advisory Committee for Promotion and Tenure (member, 1998-2001). Dean of Medicine's Search committee for Chair of Microbiology and Immunology (member, 1993-1994). Dean of Medicine's Search committee for Chair of Microbiology and Immunology (member, 1999).

6 Faculty of Medicine Postgraduate Awards Committee (member, 1998- 2001). Dean of Medicine's committee for coordination of Undergraduate Immunology programs (Chair, 1995-1996). Faculty of Medicine Animal Care Committee (member, 1997-1999; Chair, 2000). University Animal Care Committee (member 2000).

4.6 Sunnybrook Health Sciences Center Committees Research Executive Committee (member, 2005-2006) Molecular and Cell Biology Search Committee (member, 2001-2003) Molecular and Cell Biology Search Committee (member 2004-present)

4.7 National committees

Workshop co-ordinator and organizing committee member for the 4th Canadian Society for Immunology Meeting, March 1990, Mont-Gabriel, Quebec. Organizer of the 6th Canadian Society for Immunology Meeting, March 1992, Mont-Gabriel, Quebec. Organizer of the 8th Canadian Society for Immunology Meeting, March 1994, Sainte-Adèle, Quebec. Organizer of the 10th Canadian Society for Immunology Meeting, March 1996, Sainte-Adèle, Quebec. Organizer of the 12th Canadian Society for Immunology Meeting, March 1998, Sainte-Adeèle, Quebec. Chairman of the Scientific Program committee for the 14th Canadian Society for Immunology Meeting, March 2000, Chateau Bromont, Quebec. Chairman of the Scientific Program Committee for the 15th Canadian Society for Immunology Meeting, April 2001, Lake Louise, Alberta. Member of the Scientific Program Committee for the 16th Canadian Society for Immunology Meeting, April 2002, Blue Mountain, Ontario. Member of the Scientific Program Committee for the 17th Canadian Society for Immunology Meeting, April 2003, Lake Louise, Alberta. Member of the Scientific Program Committee for the 18th Canadian Society for Immunology Meeting, April 2005., Whistler, British Columbia. Chair of the 4th CFBS Northern Lights Symposium on Infection and Immunity, October 2006, Ottawa, Ontario. Health Canada Scientific Advisory Committee for HIV Therapies (member, 2003- 2009).

7 Health Canada Scientific Advisory Committee for Infectious Disease Therapies (member 2009-present). Stemnet National Center of Excellence Training Awards Committee (member 2009-present).

4.8 International committees

Convening chairman and organizer of the 1st International Avian CD Nomenclature Workshop. Montreal, June 1991. Convening chairman of the Avian CD Nomenclature committee of the International Union of Immunology Societies (1991-2001). Member of the Scientific Program Committee for the 12th International Congress of Immunology, July 2004, Montreal, Quebec. Vice-Chair for the 7th International Veterinary Immunology Symposium, July 2004, Quebec City, Quebec. Member of the General Assembly: International Union of Immunology Societies: 2004-2010.

8 C. Academic History

1. Research Outline

My laboratory has a long standing interest in defining the molecular processes that regulate the development of the B lymphocyte lineage, an interest which originated during my graduate studies in London, U.K. Funding for this work from the Canadian MRC and subsequently CIHR has been continuous since my establishment at McGill University.

Experimental systems The model system we use is the developing chick embryo. This model offers a number of advantages as compared to more widely used murine systems while at the same time yielding insights that are relevant to all higher organisms including humans. The accessibility of the chick embryo to observation and experimental manipulation is unmatched by any mammalian species. This aspect is well acknowledged by developmental biologists, embryologists and neurobiologists who have extensive studied the chick embryo over the last century. This accessibility extends to the immune system where we can modify the initial stages of lymphoid lineage development using approaches that are not feasible with currently available technology in mammalian species. B lymphocyte development in birds occurs in a gut associated lymphoid organ, the bursa of Fabricius which has many of the properties associated with the gut associated Peyer's patches and appendix of mammalian species. Although mammalian B cell development in the bone marrow has been extensively studied, the relative contributions of the bone marrow and gut associated lymphoid tissue as a source of developing lymphocytes is currently unknown. This is largely a consequence of the technical difficulties intrinsic to working with mammalian gut associated lymphoid tissue and has resulted in substantial gaps in our understanding of the immune system as a whole. In contrast, the avian bursa, unlike mammalian Peyer's patches, is easy to experimentally remove or manipulate and we have developed over the last 10 years a substantial array of experimental tools to accomplish this. We have invested considerable time in developing retrovirally mediated gene transfer as an experimental tool to address questions of lymphocyte development in the chick embryo. Conventional mammalian transgenics animals are labor intensive, time consuming and costly to generate. Similarly, the use of retrovirally mediated gene transfer in mammalian models has proved difficult due to severe safety restrictions on the use of productive vectors and the less than ideal efficiency of non-productive vectors. In contrast, avian retroviruses do not infect mammalian cells and so productive avian retroviral vectors can be generated safely under standard laboratory conditions. The inoculation of chick embryos with productive avian retroviruses, engineered to contain genes of interest, leads to rapid dissemination of the virus throughout the embryo and widespread expression of the gene of interest. The biological consequences of such expression can typically be assessed shortly after hatch without requiring breeding programs to "fix" an inherited transgene. This technology makes it feasible to assess rapidly and effectively the biological properties in vivo of families of molecules, or families of site-directed mutants of a given molecule without having to generate large numbers of independent transgenic lines. The application of this technology is just beginning. I foresee that

9 over the next five to ten years these applications will expand enormously as investigators, nationally and internationally, understand the benefits of the system. a) The analysis of early B cell development We have demonstrated that the initial stages of B cell development, involving productive colonization of lymphoid follicles, can be driven by the expression of a truncated immunoglobulin (Ig) receptor which lacks the capacity to bind to antigen. This provides the first example of B cells from an otherwise normal animal in which early B development can be formally dissociated from antigen binding. We have cloned the avian homologues to the Ig receptor associated chains, Iga and Igb, responsible for signal transduction through the surface Ig receptor and by molecular modeling have identified probably sites of inter-molecular assembly of the intact receptor complex. Using the approach of retroviral gene transfer in vivo we will be able, by site directed mutagenesis, to dissect the receptor complex at a molecular level to determine amino acid motifs critical for normal B cell development and gain insight into which signal transduction pathways are operative at this stage. b) The analysis of later stage B cell development Expression of the truncated Ig receptor is not sufficient to drive the later stages of B cell development that involve cellular redistribution within lymphoid follicles and emigration to the periphery. This provides the first evidence that interaction with antigen may be required to drive the development of B cells in a gut associated lymphoid organ. We will test this directly using chimeric surface Ig receptors of defined specificity, introduced by retroviral gene transfer. Should interaction with antigen prove to be required for the later stages of B cell development in these circumstances, it would provide the first example of antigen driven B cell clonal expansion in a primary gut associated lymphoid organ. c) Molecular mechanisms of antibody diversification During B lymphocyte development in the bursa Ig V genes undergo somatic diversification be gene conversion. This powerful mechanism for generating diversity has been observed in mammalian B cells, including mouse and human, but remains best characterized in the chicken. We have recently demonstrated that in addition to gene conversion which represents a transfer of genetic material from donor pseudogene sequences into a functional V region gene, somatic hypermutation, or point mutations are observed in the bursa. This is surprising since the bursa is a primary lymphoid organ and somatic hypermutation is considered to be a reflection of antigen driven immune responses in secondary tissues. Nonetheless our results imply a role for antigen in bursal B cell development and suggest the possibility that, even in a gut associated primary lymphoid organ, antigen may drive somatic hypermutation. Critically, however, the remarkable correlation between sites of hypermutation in the V gene sequence and the borders of gene conversion events leads us to propose that the molecular process of gene conversion is triggered by somatic hypermutation. We will address this possibility directly by identifying reaction intermediates in the pathway of gene conversion. In addition, we will use retroviral gene transfer to introduce test substrates for gene conversion into developing B cells in vivo. Such substrates will be modified to include or exclude defined sites of hypermutation that will allow us to formally identify any causal relationship between somatic hypermutation and gene conversion. d) Cell transformation and cell death induced in vivo by regulated oncogene expression

10 We have recently succeeded in using retroviral gene transfer to introduce a potent B cell tropic oncogene, v-rel, into developing chick embryos under conditions where the expression of the oncogene can be regulated by tetracycline. Although established with the v-rel oncogene, this system is applicable to other transforming genes. With respect to v-rel, however, we have set up the system to address the question of whether v-rel dependent transformation is limited by the expression of other cellular genes. We predicted that if co-expression of other cellular genes was required for v-rel mediated transformation, then different stages of B cell development would be differentially susceptible to v-rel expression. By allowing B cell development to occur under conditions where v-rel is inactive, we can generate individual animals in which all stages of B cell development are established normally. When v-rel expression is induced in these animals, there is massive and polyclonal induction of peripheral B cell tumors. Remarkably, however, the immature B cells in the bursa die by apoptotic cell death. This formally demonstrates that the consequences of v-rel expression are defined by the expression of cellular genes and that depending on the spectrum of genes expressed v-rel expression leads to oncogenic transformation of cell death. We are therefore working towards defining the nature of those genes that determine the consequences of v-rel expression. Critically, however, this system provides a model in which the fate of transformed cells might be modified, not by modulating oncogene expression, but by defining and modulating normal cellular genes whose expression is required for transformation.

2. Research Awards

Graduate: 1976-1980 Wellcome studentship. Postdoctoral: 1983-1986 Imperial Cancer Research Fund Research Post- doctoral Fellowship. Faculty: 1993-1996 Fonds de la Recherche en Santé du Québec Chercheur-boursier (Senior 2). 1990-1993 Fonds de la Recherche en Santé du Québec Chercheur-boursier (Senior 1). 1987-1990 Fonds de la Recherche en Santé du Québec Chercheur-boursier (Junior 2).

Operating grants:

1987-1989 Medical Research Council of Canada. Project entitled "Control of B Lymphocyte Ontogeny". $68,000 p.a. plus $80,000 equipment. 1989-1992 Medical Research Council of Canada. Project entitled "Control of B Lymphocyte Ontogeny". $70,800 p.a. 1990-1993 National Cancer Institute of Canada. Project entitled "Retroviral transformation of the B Lymphocyte Lineage". $67,894 p.a. plus $8,000 equipment. 1992-1995 Medical Research Council of Canada. Project entitled "Control of B Lymphocyte Ontogeny". $80,612 p.a.

11 1993-1996 National Cancer Institute of Canada. Project entitled "Retroviral transformation of lymphocytes by the v-rel oncogene". $76,465 p.a. plus $8,704 equipment. 1996-1997 National Cancer Institute of Canada. Project entitled "Retroviral transformation of lymphocytes by the v-rel oncogene". $55,889 p.a. 1995-2000 Medical Research Council of Canada. Project entitled "Control of B lymphocyte Ontogeny". $78,878 p.a. plus a studentship. 2000-2005 Canadian Institutes of Health Research. Project entitled "Control of B lymphocyte Ontogeny". $142,867 p.a. plus $14,634 equipment. 2005-2010 Canadian Institutes of Health Research. Project entitled "Control of B lymphocyte Ontogeny". $152,000 p.a.

Equipment grants:

1987 Faculty of Graduate Studies and Research, McGill University. Cryopreservation freezer. $9,535.00. 1988 Medical Research Council of Canada. Group grant, Drs. Antel (P.I.), Julius, Ratcliffe and Loescher. Gammacell-1000 blood irradiator. $50,265.00. 1991 Medical Research Council of Canada. Group grant, Drs. Ratcliffe (P.I.), Julius and Osmond. FACScan, Becton-Dickenson Flow Cyto- meter. $61,380.00. 1991 National Cancer Institute of Canada. Group grant, Drs. Ratcliffe (P.I.), Julius and Osmond. FACScan, Becton-Dickenson Flow Cyto- meter. $60,107.00. 1994 Medical Research Council of Canada. Group grant, Drs. Ratcliffe (P.I.) et al. FACS Vantage (Becton Dickinson cell sorter). $175,000.00.

Equipment maintenance grants:

1995-2000 Medical Research Council of Canada. Flow cytometry facility maintenance. Group grant; Drs Ratcliffe (P.I.) et al. $47,500 p.a. 2000-2005 Canadian Institutes of Health Research. Flow cytometry facility maintenance. Group grant; Drs Ratcliffe (P.I.) et al. $60,000 p.a. plus $59,859 equipment. 2003-2004 Canadian Institutes for Health Research. Center for Cytometry and Scanning Microscopy. Group grant; Dr. J.C. Zuniga-Pflucker (P.I.) et al. $108,749 p.a.

12 2005-2010 Canadian Institutes of Health Research. Center for Cytometry and Scanning Microscopy. Group grant; Dr. J.C. Zuniga-Pflucker (P.I.) et al. $91,838 p.a.

Training grants:

2002-2009 Canadian Institutes of Health Research. Training grant in Regenerative Medicine. Group grant. Dr. G. Levy (P.I.) et al. $300,000 p.a.

2009-2015 Canadian Institutes of Health Research. Training grant in Regenerative Medicine. Group grant. Dr. G. Levy (P.I.) et al. $325,000 p.a.

D. Publications

Refereed Publications

1. Ratcliffe, M.J.H. and Ivanyi, J. Allelic exclusion of the surface expression of surface IgM allotypes on spleen and bursal B cells in the chicken. Immunogenetics. 1979. 9: 149-156. 2. Ratcliffe, M.J.H. and Ivanyi, J. Allotype suppression in the chicken. I. Generation of chronic suppression in heterozygous but not in homozygous chickens. Eur. J. Immunol. 1979. 9: 847-852 3. Ratcliffe, M.J.H. and Ivanyi, J. Allotype suppression in the chicken. II. Suppression in homozygous chickens with anti-allotype antibody and allotype disparate B cells. Eur. J. Immunol. 1981. 11: 296-300. 4. Ratcliffe, M.J.H. and Ivanyi, J. Allotype suppression in the chicken. III Analysis of the recovery from suppression by neonatally injected or maternally derived antibodies. Eur. J. Immunol. 1981. 11: 301-306. 5. Ratcliffe, M.J.H. and Ivanyi, J. Allotype suppression in the chicken. IV. Deletion of B cells and lack of suppressor cells during chronic suppression. Eur. J. Immunol. 1981. 11: 306-310. 6. Ratcliffe, M.J.H. and Julius, M.H. H-2 restricted T-B cell interactions involved in polyspecific B cell responses mediated by soluble antigen. Eur. J. Immunol. 1982. 12: 643-641. 7. Ratcliffe, M.J.H. and Julius, M.H. Two classes of bystander B cell response: activation requirements reflect those of B cells in general. J. Immunol. 1983. 131: 581-586.

13 8. Ratcliffe, M.J.H. Allotype suppression in the chicken. V. Abnormal ratios of chronically suppressed IgM and IgG isotypes. Cell. Immunol. 1984. 83: 208-214. 9. Vainio, O. and Ratcliffe, M.J.H. Proliferation of chicken peripheral blood leukocytes in response to pokeweed mitogen is macrophage dependent. Cell. Immunol. 1984. 85: 225-243. 10. Ratcliffe, M.J.H. and Julius, M.H. T dependent activation of resting B cells mediated by concanavalin A. Eur. J. Immunol. 1984. 14: 280-283. 11. Ratcliffe, M.J.H., Julius, M.H. and Kim, K.-J. Heterogeneity in the response of T cells to antigen presented by B lymphoma cells. Cell. Immunol. 1984. 88: 49-60. 12. Orme, I.M., Ratcliffe, M.J.H. and Collins, F.M. Acquired immunity to heavy infection with mycobacterium bovis BCG and its relationship to the development of non- specific unresponsiveness in vitro. Cell. Immunol. 1984. 88: 285-296. 13. Ratcliffe, M.J.H. and Mitchison, N.A. Function of Ig receptors in B cell triggering. Ann. Immunol. (Inst. Pasteur) Paris. 1984. 135D: 73-79, 105-106. 14. Owens, T., Czitrom, A.A., Gascoigne, N.R.J., Crispe, I.N., Ratcliffe, M.J.H., Lai, P.K. and Mitchison, N.A. The presentation of cell surface alloantigens to T cells. Immunobiol. 1984. 168: 189-201. 15. Pink, J.R.L., Ratcliffe, M.J.H. and Vainio, O. Immunoglobulin bearing stem cells for clones of B (bursa derived) lymphocytes. Eur. J. Immunol. 1985. 15: 617-620. 16. Ratcliffe, M.J.H. Ontogeny and cloning of B cells in the bursa of Fabricius. Immunol. Today 1985. 6: 223-227. 17. Ratcliffe, M.J.H. Lack of pre-B cells in hatched chickens. Immunol. Today 1985. 6: 349-350. 18. Vainio, O., Ratcliffe, M.J.H. and Leanderson, T. Chicken T cell growth factor: use in the generation of long-term cultured T cell lines and biochemical characterisation. Scand. J. Immunol. 1986. 23: 135-142. 19. Ratcliffe, M.J.H., Lassila, O., Pink, J.R.L. and Vainio, O. Avian B cell precursors: cell surface immunoglobulin expression is an early, possibly bursa independent event. Eur. J. Immunol. 1986. 16: 129-133. 20. Ratcliffe, M.J.H., Lassila, O., Reynolds, J., Pink, J.R.L. and Vainio, O. A re-evaluation of the function of the bursa of Fabricius. Prog. Clin. Biol. Res. 1987. 238: 3-14. 21. Mitchison, N.A. and Ratcliffe, M.J.H. B cells can be activated in more than one way. in Paradoxes in Immunology, Levy, J.G. and Nepom, G.T. Eds. CRC Press, 1987. pp. 163-169. 22. Vainio, O., Veromaa, T., Eerola, E., Toivanen, P. and Ratcliffe, M.J.H. Antigen- presenting cell-T cell interaction in the chicken is MHC class II restricted. J. Immunol. 1988. 140: 2864-2868.

14 23. Julius, M.H., Rammensee, H.-G., Ratcliffe, M.J.H., Lamers, M.C., Langhorne, J. and Kohler, G. The molecular interactions with helper T cells which limit antigen specific B cell differentiation. Eur. J. Immunol. 1988. 18: 381-386. 24. Julius, M.H., Rammensee, H.-G., Ratcliffe, M.J.H., Lamers, R., Langhorne, J. and Kohler, G. Why cognate Th-B interaction usually limits the activation of resting B cells. in The T Cell Receptor, Davis, M.M. and Kappler, J., Eds. Alan R. Liss Inc. 1988. pp. 217-227. 25. Ratcliffe, M.J.H. and Klaus, G.G.B. The biology of B cell activation. in B Lymphocytes in Human Diseases, Bird, G. and Calvert, J. Eds. Oxford University Press. 1988. pp. 102-129. 26. Ratcliffe, M.J.H. and Lamb, J.R. Lymphocyte purification, growth, cloning and functional assays. in Pharmacology of Lymphocytes. Handbook of Experimental Pharmacology, Moorley, J. and Bray, M.A. Eds. Springer-Verlag A.G. 1988. 85: 319- 343. 27. Ratcliffe, M.J.H. Generation of immunoglobulin heavy chain diversity subsequent to cell surface immunoglobulin expression in the avian bursa of Fabricius. J. Exp. Med. 1989. 170: 1165-1173. 28. Ratcliffe, M.J.H. Development of the avian B lymphocyte lineage. CRC Crit. Rev. Poult. Biol. 1989. 2: 207-234. 29. Huffnagle, G., Ratcliffe, M.J.H. and Humphries, E.H. Bu-2, a cell surface antigen present on distinct avian hematopoetic lineages, is expressed in germinal centers. Hybridoma 1989. 8: 589-604. 30. Ratcliffe, M.J.H. and Tkalec, L. Cross-linking of the surface immunoglobulin of lymphocytes from the bursa of Fabricius results in second messenger generation. Eur. J. Immunol. 1990. 20: 1073-1078. 31. Ratcliffe, M.J.H. and Paramithiotis, E. The end can justify the means. Semin. Immunol. 1990. 2: 217-226. 32. Ratcliffe, M.J.H. (Ed.) B Lymphocyte Development. Semin. Immunol. 1990. 2: 165- 226. 33. Veillette, A. and Ratcliffe, M.J.H. Avian CD4 and CD8 interact with a cellular tyrosine protein kinase homologous to mammalian p56lck. Eur. J. Immunol. 1991. 21: 397- 401. 34. Benatar, T., Iacampo, S., Tkalec, L. and Ratcliffe, M.J.H. Expression of immunoglobulin genes in the avian embryo bone marrow revealed by retroviral transformation. Eur. J. Immunol. 1991. 21: 2529-2536. 35. Paramithiotis, E., Tkalec, L. and Ratcliffe, M.J.H. High levels of CD45 are expressed co-ordinately with CD4 and CD8 on avian thymocytes. J. Immunol. 1991. 147: 3710- 3717.

15 36. Ratcliffe, M.J.H., Coggeshall, K.M., Newell, M.K. and Julius, M.H. T cell receptor oligomerisation but not dimerisation, induces increased cytosolic calcium concen- trations and reveals a lack of stable association between CD4 and the T cell receptor complex. J. Immunol. 1992. 148: 1643-1651. 37. Srikumar, R., Cain, A.C., Vachon, V., Richardson, C.R., Ratcliffe, M.J.H., Saarinen, L., Käyhty, H., Mäkelä, P.H. and Coulton, J.W. Monoclonal antibodies specific to porin of Haemophilus influenzae type b: localization of their cognate epitopes and tests of their biological activities. Mol. Microbiol. 1992. 6: 665-676. 38. Chow, L.M.C., Ratcliffe, M.J.H. and Veillette, A. tkl is the avian homologue of the mammalian lck tyrosine protein kinase gene. Mol. Cell. Biol. 1992. 12: 1226-1233. 39. Benatar, T., Tkalec, L. and Ratcliffe, M.J.H. Stocastic rearrangement of immunoglobulin variable region genes in chicken B cell development. Proc Natl. Acad. Sci. USA. 1992. 89: 7615-7619. 40. Reddy, S.K., Silim, A. and Ratcliffe, M.J.H. Biological roles of the major capsid proteins and relationships between the two existing serotypes of infectious bursal disease virus. Arch. Virol. 1992. 127: 209-222. 41. Srikumar, R., Dahan, D., Gras, M.F., Ratcliffe, M.J.H. , van Alphen, L. and Coulton, J.W. Antigenic sites on porin of Haemophilus influenzae type b: mapping with synthetic peptides and evaluation of structure predictions. J. Bacteriol. 1992. 174: 4007-4016. 42. Marmor, M.D., Benatar, T. and Ratcliffe, M.J.H. Retroviral transformation in vitro of chicken T cells expressing either ab or gd T cell receptors by reticuloendotheliosis virus strain T. J. Exp. Med. 1993. 177: 647-656. 43. Ratcliffe, M.J.H., Benatar, T., Coumidis, A., Iacampo, S. and Marmor, M.D. Retroviral transformation as an approach to analyzing early stages of chicken B lymphocyte development. Les colloques de l’I.N.R.A. 1993. 62: 331-336. 44. Paramithiotis, E. and Ratcliffe, M.J.H. Bursa dependent subpopulations of peripheral B lymphocytes in chicken blood. Eur. J. Immunol. 1993. 23: 96-102. 45. Reddy, S.K., Ratcliffe, M.J.H. and Silim, A. Flow cytometric analysis of the neutralizing immune response against infectious bursal disease virus using avian retrovirus-transformed lymphoblastoid cell lines. J. Virol. Mthds. 1993. 44: 167-178. 46. Benatar, T. and Ratcliffe, M.J.H. Polymorphism of the functional immunoglobulin variable region genes in the chicken by exchange of sequence with donor pseudogenes. Eur. J. Immunol. 1993. 23: 2448-2453. 47. Ratcliffe, M.J.H., Boyd, R., Chen, C.H. and Vainio, O. Avian CD Nomenclature workshops, Montreal, June 1991, Budapest, August 1992 and Tours, September 1992. Vet. Immunol. Immunopathol. 1993. 38: 375-386. 48. Paramithiotis, E. and Ratcliffe, M.J.H. Bursa dependent and independent peripheral B cell populations in the chicken. Les colloques de l’I.N.R.A. 1993. 62: 325-330.

16 49. Ratcliffe, M.J.H. Ligation of cell surface immunoglobulin in the chicken bursa of Fabricius. Res. Immunol. 1993. 144: 450-455. 50. Paramithiotis, E. and Ratcliffe, M.J.H. B cell emigration directly from the cortex of lymphoid follicles in the bursa of Fabricius. Eur. J. Immunol. 1994. 24: 458-463. 51. Paramithiotis, E. and Ratcliffe, M.J.H. Survivors of bursal B cell production and emigration. Poult Sci. 1994. 73: 991-997. 52. Moeck, G.S., Bazzaz, B.S.F., Gras, M.F., Ravi, T.S., Ratcliffe, M.J.H. and Coulton, J.W. Genetic insertion of a reporter epitope in the ferrichrome-iron receptor of Escherichia coli K-12. J. Bacteriol. 1994. 176: 4250-4259. 53. Ratcliffe, M.J.H. and Jacobsen, K. Rearrangement and diversification of immunoglobulin genes in chicken B cell development. Semin. Immunol. 1994. 6: 175-184. 54. Paramithiotis, E. Jacobsen, K. and Ratcliffe, M.J.H. Loss of cell surface immunoglobulin expression precedes B cell death by apoptosis in the bursa of Fabricius. J. Exp. Med. 1995. 181: 105-113. 55. Tregaskes, C.A., Kong, F.K., Paramithiotis, E., Chen, C.L., Ratcliffe, M.J.H., Davison, F., and Young, J. Identification and analysis of the expression of CD8aa and CD8ab isoforms in chickens reveals a major TCRgd CD8aa subset of intestinal intraepithelial lymphocytes. J. Immunol. 1995. 154: 4885-4494. 56. Chan, S.L., Alizadeh-Khiavi, K., Chronopoulos, S., Li, W., Fried, V., Smith, H.T., Butt, T., Ratcliffe, M.J.H. and Ali-Kahn, Z. Recombinant and amyloid-associated ubiquitin during in vivo amyloidogenesis. Int. J. Clin. Invest. 1995. 2 191-194. 57. Moeck, G.S., Ratcliffe, M.J.H. and Coulton, J.W. Topological analysis of the Escherichia coli ferrichrome-iron receptor using monoclonal antibodies. J. Bacteriol. 1995. 177: 6118-6125. 58. Jacobsen, K.A., Paramithiotis, E., Ewert, D.L. and Ratcliffe, M.J.H. Apoptotic cell death in the chicken bursa of Fabricius. In Mechanisms of Lymphocyte Activation and Immune Regulation VI. Cell Cycle and Programmed Cell Death in the Immune System. Gupta, S. and Cohen, J.J. (Eds.), Plenum Publishing Corp., 1996. pp 155-166. 59. Paramithiotis, E. and Ratcliffe, M.J.H. Evidence for phenotypic heterogeneity among B cells emigrating from the bursa of Fabricius. A reflection of functional diversity? Curr. Top. Microbiol. Immunol. 1996. 212: 27-34. 60. Ratcliffe, M.J.H., Paramithiotis, E., Coumidis, A., Sayegh, C.E., Demaries, S.L., Martinez, O. and Jacobsen, K.A. The bursa of Fabricius and its role in avian B lymphocyte development. In Poultry Immunology, Davison, F., Payne, J. and Morris, T.R. (Eds.), Carfax, 1996. pp11-30. 61. Ratcliffe, M.J.H. The study of B cell differentiation. In Manual of Immunological Methods, 2nd Edition, Lefkovits, I. (Ed), Academic Press, 1997. pp 2200-2211.

17 62. Ratcliffe, M.J.H. Chicken immunoglobulin isotypes and allotypes. In Handbook of Experimental Immunology, 5th edition, Weir, D.W., Herzenberg, L.A. and Herzenberg, L.A. (Eds), Blackwell Scientific Publications, Oxford, 1997. pp 24.1-24.15. 63. Jeurissen, S.H.M., Vainio, O. and Ratcliffe, M.J.H. Leukocyte markers in the chicken. In Handbook of Vertebrate Immunology, Pastoret, P.P., Griebel, P. and Govaerts, H. (Eds.), Academic Press Ltd., London. 1998. pp81-85. 64. Demaries, S.L. and Ratcliffe, M.J.H. Cell surface and secreted immunoglobulins in chicken B cell development. In Handbook of Vertebrate Immunology, Pastoret, P.P., Griebel, P. and Govaerts, H. (Eds.), Academic Press Ltd., London. 1998. pp89-92. 65. Sayegh, C.E., Drury, G.L., Demaries, S.L., Iacampo, S. and Ratcliffe, M.J.H. Colonization of the bursa of Fabricius by sIg+ B cell precursors lacking V(D)J encoded determinants: a clonal analysis. In 10th International Congress of Immunology, Talwar, G.P., Nath, I., Ganguly, N.K. and Rao, K.V.S. (Eds.), Monduzzi Editore, Bologna, Italy. 1998. pp 111-114. 66. Sayegh, C.E., Demaries, S.L., Iacampo, S. and Ratcliffe, M.J.H. Development of B cells that lack V(D)J-encoded determinants in the avian embryo bursa of Fabricius. Proc. Natl. Acad. Sci. USA. 1999. 96: 10806-10811. 67. Sayegh, C.E., Drury, G.L. and Ratcliffe, M.J.H. Efficient antibody diversification by gene conversion in vivo in the absence of selection for V(D)J-encoded determinants. EMBO J. 1999. 18: 6319-6328. 68. Sayegh, C.E., Rao, M.A. and Ratcliffe, M.J.H. Avian B cell development: lessons from transgenic models. Vet. Immunol. Immunopathol. 1999. 72: 31-37. 69. Sayegh, C.E., Demaries, S.L., Friedmann, J., Pike, K. and Ratcliffe, M.J.H. The chicken B cell receptor complex and its role in avian B cell development. Immunol. Rev. 2000. 175: 187-200. 70. Sayegh, C.E. and Ratcliffe, M.J.H. Perinatal deletion of B cells expressing surface immunoglobulin molecules that lack V(D)J-encoded determinants in the bursa of Fabricius is not due to intra-follicular competition. J. Immunol. 2000. 164: 5041- 5048. 71. Pike, K.A., Friedmann, J.E., Iacampo, S., Sandhu, R. K. and Ratcliffe, M.J.H. Replacement of surface immunoglobulin expression by the cytoplasmic domains of the Iga/b heterodimer in early B cell development. In Proceedings of the 6th AIRG Meeting, Schat, T., Dietert, R., Marsh, J. and Naqi, S. (Eds.), AAAP Press. 2001. 90-97. 72. Ratcliffe, M.J.H. and Pike, K.A. Influence of antibody diversification on the mechanism of haplotype exclusion of immunoglobulin gene expression. Semin. Immunol. 2002. 14: 199-205. Second round comments on the issue of haplotype exclusion. ibid 14: 233. Final round comments on the issue of haplotype exclusion. ibid 14: 243-244. Final final round comments on the issue of haplotype exclusion. ibid 14: 245.

18 73. Pike, K.A. and Ratcliffe, M.J.H. Cell surface immunoglobulin receptors in B cell development. Semin. Immunol. 2002. 14: 351-358. 74. Ratcliffe, M.J.H. B cell development in gut associated lymphoid tissues. Vet. Immunol. Immunopathol. 2002. 87: 337-341. 75. Pike, K.A., Baig, E. and Ratcliffe, M.J.H. Distinct roles for Iga and Igb in chicken B cell development. Immunol. Rev. 2004. 197: 10-15. 76. Pike, K.A., Iacampo, S., Friedmann, J.E. and Ratcliffe, M.J.H. The cytoplasmic domain of Iga is necessary and sufficient to support efficient early B cell development. J. Immunol. 2004. 172: 2210-2218. 77. Pike, K.A. and Ratcliffe, M.J.H. Dual requirement for the Iga immunoreceptor tyrosine-based activation motif (ITAM) and a conserved non-Iga ITAM tyrosine in supporting Igab-mediated B cell development. J. Immunol. 2005. 174: 2012-2020. 78. Aliahmad, P., Pike, K.A. and Ratcliffe, M.J.H. Cell surface immunoglobulin regulated check-points in chicken B cell development. Vet. Immunol. Immunopathol. 2005. 108: 3-9. 79. Ratcliffe, M.J.H. Antibodies, immunoglobulin genes and the bursa of Fabricius in chicken B cell development. Dev. Comp. Immunol. 2006. 30: 101-118. 80. Pike, K.A. and Ratcliffe, M.J.H. Ligand-independent signaling during early avian B cell development. Immunol Res. 2006. 35: 103-116. 81. Imamura, Y., Oda, A., Katahira, T., Bundo, K., Pike, K.A., Ratcliffe, M.J.H. and Kitamura, D. BLNK binds active H-Ras to promote B cell receptor-mediated capping and ERK activation. J. Biol. Chem. 2009. 284: 9804-9813.

82. Chan, E.T., Quon, G.T., Chua, G., Babak, T., Trochesset, M., Zirngibl, R.A., Aubin. J., Ratcliffe, M.J.H., Wilde, A., Brudno, M., Morris, Q.D. and Hughes, T.R. Conservation of core gene expression in vertebrate tissues. J Biol. 2009. 8: 33-33.17.

83. Kothlow, S., Schenk-Weibhauser, K., Ratcliffe, M.J.H. and Kaspers, B. The RCAS retroviral gene transfer technology: an efficient system for functional in vivo studies with soluble proteins in the chicken. Submitted for publication.

84. Akram, A., Williams, D., Ratcliffe, M.J.H. Slutsky, A.S. and DosSantos, C.C. Pattern of HLA alele co-expression influences immunodominance of anti-influenza CTL responses. Sunbitted for publication.

85. Agard, E., Dervovic, J., Chou, M.-Y., Lewis, S. and Ratcliffe, M.J.H. Frequent DH to DJH rearrangement at the chicken immunoglobulin heavy chain locus mediated by efficient spacer sequence dependent RSS12/12 recombination. in preparation. 86. Neschadim, A. and Ratcliffe, M.J.H. A high frequency of immunoglobulin heavy and light chain combinations isolated from the chicken bursa of Fabricius fail to pair. In preparation.

19 E. Presentations and Special Lectures

National and International Symposia and Workshop Chairmanships:

Workshop chairman (B cell subpopulations). International Union of Immunology Societies 6th International Immunology Congress, Toronto 1986. Symposium co-chairman (Immunoglobulin genes). 6th Canadian Society for Immunology Meeting, Mont Gabriel, March 1992. Workshop chairman (2nd International Avian CD Nomenclature Workshop). 3rd International Veterinary Immunology Symposium, Budapest, August 1992. Symposium chairman (Developmental and Comparative Immunology). 3rd International Veterinary Immunology Symposium, Budapest, Hungary, August 1992. Workshop chairman (3rd International Avian CD Nomenclature Workshop). Avian Immunology Research Group Meeting, Tours, France, September 1992. Symposium co-chairman (Ontogeny and lymphoid development). Avian Immunology Research Group Meeting, Tours, France, September 1992. Workshop chairman (Antigen expression in lymphocyte development). 7th Canadian Society for Immunology Meeting, Lake Louise, Alberta, March 1993. Workshop chairman (4th International Avian CD Nomenclature Workshop). Avian Immunology Symposium, East Lansing, July 1993. Symposium co-chairman (B cell development). Avian Immunology Research Group Meeting, Reading, U.K., March 1994. Workshop chairman (5th International Avian CD Nomenclature Workshop). Avian Immunology Research Group Meeting, Compton, U.K., March 1994. Symposium chairman (T lymphocyte development) World Poultry Science Association Meeting, Reading, U.K. September 1995. Symposium co-chairman (Avian Biology: The Immune System and Environmental Stressors) American Society of Zoologists Meeting, Washington, U.S.A., December 1995. Symposium co-chairman (Evolutionary Aspects of the Immune System) International Symposium on the Challenges of Lower Vertebrates to Immunology, Kyoto, Japan, November 1997. Workshop chairman (6th International Avian CD Nomenclature Workshop). Avian Immunology Research Group Meeting, Turku, Finland, June 1998. Symposium Chairman (Avian Immunology) 5th International Veterinary Immunology Symposium, Ludhiana, India, November 1998. Workshop co-chairman (Lymphocyte development). 14th Canadian Society for Immunology Meeting, Chateau Bromont, Quebec, March 2000. Symposium Chairman (B cells in secondary lymphoid organs) 15th Canadian Society for Immunology Meeting, Lake Louise, Alberta, April 2001.

20 Symposium Chairman (B cells and Antibodies) 6th International Veterinary Immunology Symposium, Uppsala, Sweden, July 2001. Symposium co-chair (Bursal Physiology and Oncogenesis) International Workshop on Experimental Models from the Bursa of Fabricius, Seattle, Washington, USA, October 2002. Minisymposium Co-chair (Mechanisms of B Cell Diversity) 12th International Congress of Immunology. Montreal, Que. July 2004. Minisymposium Co-chair (Evolution of the Immune System) 13th International Congress of Immunology. Rio de Janeiro, Brazil, August 2007.

National and International Symposium Presentations:

British Society for Immunology Summer Meeting, Bristol, UK, July 1979. Allotype suppression in the chicken. International Conference on Avian Immunology, Philadelphia, USA, July 1986. B lymph- ocyte ontogeny in the chicken. 4th Canadian Society for Immunology Meeting, Mont-Gabriel, March 1990. Generation of B cells and Immunoglobulin diversity in the avian bursa of Fabricius. 6th Canadian Society for Immunology Meeting, Mont-Gabriel, March 1992. Chicken Ig genes and concluding remarks. American Veterinary Medicine Association Annual Meeting, Boston, USA, August 1992. High frequency retroviral transformation of chicken T cells expressing either ???or ?? T cell receptors. 3rd International Veterinary Immunology Symposium, Budapest, Hungary, August 1992. Early B cell development in the chicken. Avian Immunology Research Group Meeting, Tours, France, September 1992. Allelic variation of chicken immunoglobulin genes and the sequence of their rearrange- ment. Avian Immunology Symposium, East Lansing, USA, July 1993. Bursal and post-bursal B cell development in the chicken. Avian Immunology Research Group Meeting, Reading, U.K., March 1994. Life and death in chicken B cell development. Immunology and Developmental Biology of the Chicken, Basel, Switzerland, December 1994. Life and death in the B cell lineage. World Poultry Science Association Meeting, Reading, U.K., September 1995. Regulation of B lymphocyte development. American Society of Zoologists, Washington, U.S.A., December 1995. Regulation of lymphoid development and activation.

21 6th International Conference on Lymphocyte Activation and Immune Regulation, Newport Beach, U.S.A., February 1996. Apoptotic cell death and its regulation in the avian B lymphoid system. International Symposium on the Challenges of Lower Vertebrates to Immunology, Kyoto, Japan, November 1997. Avian B lymphocyte development and the bursa of Fabricius. 5th Avian Immunology Research group Meeting, Turku, Finland, June 1998. No obligatory ligand for V(D)J encoded determinants of the pre-diversified B cell surface immunoglobulin receptor. 5th International Veterinary Immunology Symposium, Ludhiana, India, November 1998. Avian B cell development: lessons from transgenic models. 6th Annual Congress of the British Society for Immunology, Harrogate, U.K. December 1998. Transgenic regulation of avian B cell development. 15th Canadian Society for Immunology Meeting, Lake Louise, Alberta, April 2001. Evolution of lymphopoiesis from a secondary lymphoid organ. 6th International Veterinary Immunology Symposium, Uppsala, Sweden, July 2001. Membrane proximal expression of the cytoplasmic domain of Iga is sufficient to drive B cell development. AAVI-ACVM 2001 Symposium, St. Louis, Missouri, USA, November 2001. The role of the surface immunoglobulin receptor complex in chicken B cell development. International Workshop on Experimental Models from the Bursa of Fabricius, Seattle, Washington, USA. October 2002. Basal signaling through the cytoplasmic domain of Iga is sufficient to support early B cell development. 12th International Congress of Immunology, Montreal, Que. July 2004. Diverse mechanisms of antibody diversity. (Minisymposium presentation). 7th International Veterinary Immunology Symposium, Quebec City, Que. July 2004. Chicken B cell development: a paradigm for the generation of B cell repertoires in the gut. 13th International Congress of Immunology, Rio de Janeiro, Brazil, August 2007. Evolution of primary B cell lymphopoeisis from a secondary lymphoid organ.

22 Selected Invited seminars and lectures (1990-present):

Department of Immunology, Rush Presbyterian Hospital, University of Chicago. March 1990. Avian B cell development. Center for Host Resistance, McGill University. March 1991. How birds do it! Department of Anatomy, McGill University. November 1991. Avian B cell development. Department of Biochemistry, University of Sherbrooke. February 1992. Immunoglobulin genes in avian B cell development. Department of Immunology, University of Toronto. February 1992. Immunoglobulin genes in avian B cell development. Department of Immunology, University of Glasgow, U.K. April 1992. Immunoglobulin genes in avian B cell development. Department of Immunology, The Medical School, Newcastle upon Tyne, U.K. April 1992. Immunoglobulin genes in avian B cell development. Institute for Animal Health, Compton, U.K. April 1992. Immunoglobulin genes in avian B cell development. Department of Pathology, University of Cambridge, U.K. April 1992. Immunoglobulin genes in avian B cell development. Central Research Division, Pfizer Inc., Groton, CT. May 1992. Avian B cell development. Department of Microbiology, State University of New York at Stony Brook. November 1992. Normal and transformed models of avian B lymphocyte development. USDA-RPRL, East Lansing, MI. December 1992. Normal and Transformed Models of avian B lymphocyte development. Department of Medical Physiology, University of Calgary. March 1993. B cell development: how birds do it. Department of Avian Sciences, Cornell University. November 1993. Life and death in the avian bursa of Fabricius. Montreal General Hospital Research Institute, McGill University. February 1994. Life and death in chicken B cell development. Basel Institute for Immunology, Basel, Switzerland, December 1994. Life and death in chicken B cell development. Max Plank Institute for Immunobiology, Frieburg, Germany, December 1994. Life and death in chicken B cell development. Institute for Genetics, Cologne, Germany, December 1994. Life and death in chicken B cell development. School of Biological Sciences, University of Manchester, Manchester, U.K., September 1995. Life and death in chicken B cell development. Central Research Division, Pfizer Inc., Groton, CT, U.S.A., December 1995. Normal and transgenic models of chicken B cell development.

23 Department of Immunology, University of Toronto, January 1996. Life and death in chicken B cell development. City of Hope Medical Center, Duarte, California, U.S.A., February 1996. Avian B lymphocyte development. Department of Microbiology and Immunology, University of California San Francisco, San Francisco, California, U.S.A., February 1996. Life and death in avian B cell development. Department of Anatomy, McGill University, Montreal, February 1996. Avian B lymphocyte development. Department of Veterinary Microbiology and Immunology, University of Guelph, Guelph, Ont., June 1996. Life and death in avian B cell development. Department of Medical Microbiology, University of Calgary, Calgary, Alta., May 1996. Development of avian B lymphocytes. Department of Microbiology and Immunology, University of Western Ontario, London, Ont., November 1996. Development of B lymphocyte lineages. Department of Immunology, University of Toronto, Toronto, Ont., February 1997. Development of chicken B lymphocyte lineages. Department of Microbiology and Immunology, University of Sherbrooke, Sherbrooke, Que., April 1997. Development of chicken B lymphocyte lineages. Department of Immunology, University of Tokyo, Tokyo, Japan, November 1997. Regulation of apoptosis in avian B cell development. Department of Pathology, CMU, University of Geneva, Geneva, Switzerland, June 1998. Transgenic regulation of avian B cell development. Basel Institute for Immunology, Basel, Switzerland, June 1998. Avian B lymphocyte development regulated by retroviral gene transfer. University Pierre and Marie Curie, Paris, France, July 1998. Transgenic regulation of avian B cell development. Department of Immunology, University College London, London, U.K., July 1998. Avian B cell development regulated by retroviral gene transfer. Department of Immunology, University of Glasgow, Glasgow, U.K., July 1998. Avian B cell development regulated by retroviral gene transfer. Montreal Children's Hospital research Institute, Montreal, Que., November 1998. Trans- genic regulation of avian B lymphocyte development. Institute for Animal Health, Compton, U.K. December 1998. Cell surface immunoglobulin in chicken B cell development. Department of Immunology, University of Toronto, Toronto, Ont., November 1999. The chicken sIg receptor complex and its role in B lineage development. Department of Immunology, University of Toronto, Toronto, Ont., May 2000. The role of the surface immunoglobulin receptor complex in B lymphocyte development.

24 Department of Microbiology, Loyola University, Chicago, IL, USA. September 2000. The role of the surface immunoglobulin receptor complex in B lymphocyte development. Department of Anatomy and Cell Biology, University of Calgary, Calgary, Alta. April 2001. The chicken sIg receptor complex and its role in B lineage development. Heinrich-Pette-Institute, Hamburg, Germany, July 2001. The role of the surface immunoglobulin receptor complex in B lymphocyte development. Department of Pathobiology, University of Guelph, Guelph, Ont., November 2001. The role of the surface immunoglobulin receptor complex in B lymphocyte development. CIHR Transplantation Seminar Series, University of Toronto, Toronto, Ont., November 2001. B lymphocyte development dissected by retroviral gene transfer. Department of Microbiology and Immunology, Université de Montréal, Que. January 2002. The role of the surface immunoglobulin receptor complex in B lymphocyte development. Biotechnology Research Center, University of British Columbia, Vancouver, BC, October 2002. The role of the surface immunoglobulin complex in B lymphocyte development. Albert Einstein College of Medicine, New York, NY, USA. September 2003. Role of surface immunoglobulin in B cell development. Origen Therapeutics, Burlingame, CA, USA. March 2004. Surface immunoglobulin and B cell development. Michigan State University, East Lansing, MI, USA. May 2005. Regulation of B cell development by the surface immunoglobulin receptor complex. Immunology Research Group, University of Calgary, June 2005. Regulation of B cell development by the surface immunoglobulin receptor complex. CIHR Transplantation Group, Toronto, Ontario, February 2006. Immunoglobulin gene expression and B cell development. Center for Women’s Health Symposium on Emergent Paradigms in Women’s Health, Toronto, Ontario, May 2006. The immune system. Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, July 2009. Regulation of B cell development in gut associated lymphoid tissue.

25 F. Teaching and design 1986-2001, Department of Microbiology and Immunology, McGill University; 2001-present, Department of Immunology, University of Toronto

1. Courses taught 2002-present Immunobiology (IMM335Y) Course coordinator and lecturer, 6 hours. Design and implementation of new course for Immunology Specialists. 2001-present Immunobiology (IMM334Y) Course coordinator and lecturer, 12 hours. 2001-present Recent Advances in Immunology (IMM1016) lecturer, 4 hours. 2003-present Pathobiology of Disease (Undergraduate Medical Curriculum, year 2) lecturer, 1 hour. 2003-present Developmental Immunology (IMM429H) lecturer, 2 hours. 2003-present The Immune Response (IMM430H) lecturer, 2 hours. 2009-present Immunology of Emerging Infectious Diseases, Shantou University, China, lecturer, 12 hours.

1988-2001 Advanced Immunology (528-414A) Course coordinator and lecturer, 8 hours. Design and implementation of new course. 1987-2001 Immunology (528-314B) Course coordinator (1994-2001) and lecturer 12 hours. 1991 Selected Topics in Lymphocyte Development (Graduate Reading and Conference course) Course coordinator. 1995 Cell and Molecular Events in Lymphocyte Development (Graduate Reading and Conference course) Course coordinator. 2001 Recent Advances in Lymphocyte development (Graduate Reading and Conference course) Course coordinator. 1992-2001 Academic Advisor, Department of Microbiology and Immunology.

26 2. Undergraduate student research project supervision

Summer students:

Sandra Iacampo (1990) Sham Baig (2002) Spencer Lister (1991) Ephraim Tang (2003) Mina Marmor (1991) Raj Satkunisavam (2003) Mina Marmor (1992) Christina Grava (2004) Vasiliki Bitzas (1993) Ania Radziszewska (2004) Camil Sayegh (1994) Gladys Wong (2005) Sandra Demaries (1994) Joseph Fiorelino (2005) Nathalie Earl (1995) Pamela Tsao (2005, 2006) Martin Chang (1995) Jennifer Li (2006) Sandra Demaries (1995) Jerome Chan (2006) Benjamin Mathew (1995) Michael Orthofer (2006) University Of Kristie Devreitis (1996) Vienna Iris Doyle (1996) Dianne Wu (2007) Peggy Lau (1996) David Shih (2007) Gillian Drury (1998) Harveer Mihal (2007) Kelly Pike (1999) Linda Zhao (2008) Jennifer Friedmann (1999) Christopher Yao (2009) Krista Heinonen (2000) Nhat Tran (2009) Roop Kaur Sandhu (2000) Yurij Baglaekno (2009) Ming-Yi Chou (2002)

Final Year Research Project Students

Nathalie Riebel (1987-88) Microbiology and Immunology Honors Program. David Wilson (1988-89) Microbiology and Immunology Honors Program. Tania Benatar (1989-90) Microbiology and Immunology Honors Program. Winner of the E.D.G. Murray Prize for top graduating Honors student. Jennifer Wilshire (1993) Microbiology and Immunology Honors Program. Mina Marmor (1992-93) Interdepartmental Honors Immunology Program. Sandra Demaries (1994-95) Microbiology and Immunology Honors program. Benjamin Matthew (1995-96) Microbiology and Immunology Major Program. Cemaine Tsang (1996) Microbiology and Immunology Major Program. Iris Doyle (1996-97) Microbiology and Immunology Honors Program. Peggy Lau (1996-97) Interdepartmental Honors Immunology Program. Derrick Gibbings (1997-98) Microbiology and Immunology Honors Program. Gillian Drury (1998-1999) Microbiology and Immunology Honors Program. Kelly Pike (1999-2000) Microbiology and Immunology Honors Program. Jennifer Friedmann (1999-2000) Microbiology and Immunology Honors Program.

27 Krista Heinonen (2000-2001) Microbiology and Immunology Honors Program. Roop Kaur Sandhu (2000-2001) Microbiology and Immunology Honors Program. Sham Baig (2002-2003) Immunology IMM450Y. Husam Abdel-Qadir (2002-2003) Immunology IMM450Y. Ephraiam Tang (2003-2004) Immunology IMM450Y. Raj Satkunisavam (2003-2004) Immunology IMM450Y. Christina Grava (2004-2005) Immunology IMM450Y. Ania Radziszewska (2004-2005) Immunology IMM450Y. Gladys Wong (2005-2006) Immunology IMM450Y. Joseph Fiorelino (2005-2006) Immunology IMM450Y. Jennifer Li (2006-2007) Immunology IMM450Y. Jerome Chan (2006-2007) Immunology IMM450Y. Dianne Wu (2007-2008) Immunology IMM450Y David Shih (2007-2008) Immunology IMM450Y Linda Zhao (2008-2009) Immunology IMM450Y Christopher Yao (2009-2010) Immunology IMM450Y Nhat Tran (2009-2010) Immunology IMM450Y Yurij Baglaekno (2009-2010) Immunology 450Y

3. Graduate trainees, direct supervision

Eustache Paramithiotis (Ph.D. 1994) Supported by FCAR and NSERC. Tania Benatar (M.Sc., 1992) Supported by the Cancer Research Society. Winner of the Wilfred Yaffe Award for top M.Sc. graduate (1992-3). Oswald Martinez (M.Sc., 1996) Sandra Demaries (M.Sc. 1997) Supported by a studentship from FCAR. Winner of the Wilfred Yaffe Award for top M.Sc. graduate 1997-98) Mira Rao (M.Sc. 1999) Supported by a studentship from NSERC. Karen Jacobsen (post-doctoral fellow, 1994-98) Supported by MRC post-doctoral fellowship. Camil Sayegh (Ph.D. 2000) Supported by an MRC studentship. Winner of the Becton-Dickinson prize for best student poster presentation at the 13th Canadian Society for Immunology Meeting. Kelly Pike (Ph.D. 2005) Supported by FRSQ. Parinaz Aliahmad (M.Sc. 2002) Supported by NSERC. Anton Neschadin (M.Sc. 2005) Sonja Kothlow (post-doctoral fellow, 2005) Supported by DAAD, Germany. Mani Larijani (Ph.D. 2003) co-supervisor with G. Wu. Emily Agard (Ph.D. 2005) co-supervisor with S. Lewis. Joseph Fiorelino (M.Sc. 2008) Dariush Tahamzadeh (Ph.D. in progress) Supported by CIHR. Alex Ling (Ph.D. in progress)

28 4. Graduate students indirect supervision

A. Duclos (Microbiology and Immunology, 1994-6) J. Lee (Biochemistry, 1995) J. Stewart (Microbiology and Immunology, 1993-96) L. Chow (Biochemistry, 1993) R. Srikumar (Microbiology and Immunology, 1992-96) B. Huang (Experimental Medicine, 1993-6) L. Petropolous (Microbiology and Immunology, 1995-98) X. Shan (Microbiology and Immunology, 1994-98) L. Haughn (Microbiology and Immunology, 1993-98) S. Klein (Experimental Medicine, 1994-97) G. Moeck (Microbiology and Immunology, 1992-96) D. Dahan (Microbiology and Immunology, 1993-97) J. Hu (Experimental Medicine, 1995-99) J. Albenese (Haematology, 1994-98) S. Lesage (Experimental Medicine, 1996-99) F. Phillappoussis (Microbiology and Immunology, 1998-2001) D. St. Dic (Microbiology and Immunology, 1997-2001) I. Doyle (Microbiology and Immunology, 1998-99) C. Moldovan (Microbiology and Immunology, 1998-2001) J.F. Poulin (Microbiology and Immunology, 1998-2002) K. Brassinger (Microbiology and Immunology, 1998-2001) L. Fawaz (Experimental Medicine, 2000-2001) M. Ciofani (Immunology, J.C. Zuniga-Pflucker, 2002-2007) R. de Pooter (Immunology, J.C. Zuniga-Pflucker, 2002-2008) J. Yuan (Immunology, C. Guidos, 2003-2008) C. Hammond (Medical Biophysics, D. Spaner, 2003-2008) C. Koscik (Immunology, G. Levy, 2003-2005) M.Sc 2005. D. Frieder (Immunology, A. Martin, 2003-2009) F. Guerra (Immunology, R. Rottapel, 2004-2009) E. Tang (Immunology, A. Martin, 2004-2007) D. McCarthy (Immunology, J. Gommerman, 2004-present) C. Loh (Immunology, J. Wither, 2004-present) I. Shalev (Immunology, G.Levy, 2005-2009) P. Urbanellis (Immunology, G. Levy, 2007-present)

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