I enjoy camping and good mystery novels.

 chelgaso@bccrc.ca
 http://www.geocities.com/cdhlab/

  View Publications

Department:	Cancer Endocrinology (@ the BCCRC since 1993)
Research Role:	Senior Scientist
Postdoctoral Fellows:	Min Lu
Graduate Students:	Amy Tien
Education:	Ph.D (Biochemistry), University of Alberta, 1993 M.Sc. (Biochemistry), University of Saskatchewan, 1987 B.Sc. (Hons. Biochemistry), University of Saskatchewan, 1984
Birthplace:	Canada
Phone:	604-675-8011
Fax:	604-675-8019

Research Interests:

An exciting new strategy for cancer therapy involves manipulation of the immune system to generate tumor-specific immune responses. Initial efforts involved the use of various growth factors or other agents to induce the activation and proliferation of tumor-specific T lymphocytes. Recently, an alternative approach utilizes the ability of dendritic cells (DC) to process and present antigens to naïve T cells, thus stimulating an antigen-specific immune response. More importantly, this latter method may also be useful for the development of cancer vaccines. The objective of my research is to investigate the regulation of immune cell development and function in order to devise innovative and effective regimes for the prevention or treatment of malignancies such as prostate cancer.

The immune system is delicately poised to respond to antigen in a specific and regulated fashion. However, inappropriate immune activation can lead to the development of systemic or tissue-specific autoimmune diseases. Targeted disruption of the SH2-containing inositol-5-phosphatase SHIP leads to numerous hematopoietic and immune perturbations that ultimately culminate in the development of a systemic autoimmune disease closely resembling systemic lupus erythematosus. The hypothesis underlying one of the projects in my laboratory is that perturbation in the development and/or function of DC contributes to the initiation and/or progression of autoimmune disease in this model. Phenotypic and functional characterization of wild type and SHIP-deficient DC is being carried out to address this question. In addition, tissue-specific gene targeting is being used to examine the cellular basis of autoimmunity in greater detail.

The inositol phosphatase SHIP and the protein tyrosine phosphatase SHP-1 are both negative regulators involved in establishing signaling thresholds for numerous cytokine and immune receptors. In order to determine the molecular mechanisms by which these thresholds are established regulation of B cell antigen receptor signaling is being examined in mice with mutations in one or both of these signaling molecules. These studies involve the use of "knock-in" mouse models expressing various SHIP mutants and the evaluation of cell cycle progression, apoptosis, and gene transcription following B cell antigen receptor stimulation in single and compound mutant mice.

An additional objective of my research is to determine if selected chemokines and/or chemokine receptors are novel therapeutic agents to enhance DC function as a means of overcoming the progressive immunodeficiency observed in prostate cancer. DC numbers and function are being correlated with disease progression in a transgenic mouse model of prostate cancer. The effect of primary prostate cancer cells on the expression of selected chemokines and their receptors during DC development and maturation is also being examined both in vitro and in vivo. Finally, studies will be carried out to determine if modulation of chemokine expression in the mouse prostate results in enhanced DC infiltration and migration with a consequent inhibition of tumorigenesis.