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Roger G.E. Palfree, Ph.D. Associate Professor Department of Medicine Division of Endocrinology & Metabolism Affiliated with Dept. of Microbiology and Immunology Endocrine Laboratory, Room L2.05 Royal Victoria Hospital |
Research:
Intercellular modulation of cell differentiation and effector functions.
The coordination of cell behaviour through long and short range communication with other cells is fundamental to the development and integrity of an organism like the human body. From a cell's perspective, all signals received are from its immediate environment. Many signals are provided by molecules, soluble or anchored on neighbouring cell surfaces, which bind to specific receptors on the cell surface. The types of receptor expressed by a cell determine which environmental factors will influence it. Any surface protein found on a restricted subset of cells is likely to be a specific receptor or signal molecule. One fascinating set of structurally-related surface proteins which has caught my interest is the Ly-6 family. Various members of this family are found on subsets of developing haematopoietic cells and mature leucocytes, and also in certain other tissues, including kidney, testis, placenta and adrenal. I believe that several members of the Ly-6 family are involved in the modulation of haematopoietic cell development and immune responses. The expression of three of them is known to be strongly induced by cytokines, most notably interferons. Six members of the family have been clearly defined in mouse, and two of these have newly discovered counterparts in human (Reviewed in: Palfree, R.G.E. 1996. Tissue Antigens 48: 71-79). One human homologue we are currently investigating is most similar to mouse TSA-1, an Ly-6 member found on pluripotent bone marrow cells and thymocytes (Shan, X., et al. 1998. J. Immunol. 160: 197-208). Its expression is induced during retinoic acid driven differentiation of promyelocytic leukaemia cells, and it may be a marker for the differentiated state. We are trying to identify the natural ligands for Ly-6 molecules as a crucial step toward understanding their functions, Studies in this area are likely to add to our understanding of cell differentiation during haematopoiesis, and the modulation of immune effector cell function. They may be useful in providing diagnostic reagents, and refining our control over cell differentiation. It is to be hoped that a more enlightened funding policy will soon reverse the disturbing decline in support for this type of discovery-level basic research. Other areas of interest, primarily through collaborative research, include the interaction between immune and endocrine systems, and a novel family of growth factors called granulins.
Selected Publications:
Palfree, R.G.E. and Hammerling, U. 1986. Biochemical Characterization of the Murine Activated Lymphocyte Alloantigen Ly-6E.1 Controlled by the Ly-6 Locus. J. Immunol. 136: 594-600.
Palfree, R.G.E., Dumont, F.J. and Hammerling, U. 1986. Ly-6A.2 and Ly-6E.1 molecules are antithetical and identical with MALA-1. Immunogenetics 23: 197-207.
Palfree, R.G.E., Sirlin, S., Dumont, F.J. and Hammerling, U. 1988. N-terminal and cDNA characterization of murine lymphocyte antigen Ly-6C.2. J. Immunol. 140: 305-310.
Toulon, M., Palfree, R.G.E., Palfree, S., Dumont, F.J. and Hammerling, U. 1988. Ly-6A/E antigen of murine T cells is associated with a distinct pathway of activation: Requirements for interferon and exogenous interleukin 2. Eur. J. Immunol. 18: 937-942.
Bhandari, V., Palfree, R.G.E. and Bateman, A. 1992. Isolation of the granulin precursor cDNA from human bone marrow reveals tandem cysteine-rich granulin domains. Proc. Natl. Acad. Sci. 89: 1715-1719.
Palfree, R.G.E. 1996. Ly-6-domain proteins - New insights and new members: a C-terminal Ly-6 domain in sperm acrosomal protein SP-10. Tissue Antigens 48:71-79.
Shan, X., Bourdeau, A., Rhoton, A., Wells, D. E., Cohen, E. H., Landgraf, B.E. and Palfree, R.G.E. 1998. Characterization and mapping to human chromosome 8q24.3 of ly-6-related gene 9804 encoding an apparent homologue of mouse TSA-1. J. Immunol. 160:197-208