Dr. Colin Anderson

 

 

Our research is focused on two main goals, 1. A basic understanding the mechanisms by which the immune system can become tolerant of some antigens while at the same time responding to others, and 2. Devising ways to induce tolerance to donor islet transplants in order to generate a clinical islet transplant protocol for the treatment of diabetes that does not require continuous immunosuppressive therapy of the patient.

 

In order to study the mechanisms of tolerance vs. immunity we use T cell antigen receptor transgenic mice that have a monoclonal population of T cells specific to donor graft antigens.  This allows us to track the fate of the graft reactive T cells, both under conditions of immunity or tolerance.  We are using these models to study natural peripheral tolerance and to dissect out the factors that control indirect recognition of islet transplants.  In order to generate tolerance protocols for islet transplantation we are testing the efficacy of blocking novel costimulatory molecules and triggering coinhibitory pathways.  In a second approach for tolerance we are developing new methods of establishing chimerism with donor cells.  In the clinical setting, we are analyzing the status of T cells in peripheral blood of clinical islet transplant recipients with the goal of generating prognostic markers for tolerance and the possibility of withdrawing immunosuppressive therapy.

 

These studies are carried out in our Tolerance Laboratory headed jointly by Dr. James Shapiro, and myself and through collaborations with other members of the Islet Transplant Group, and members of other Faculties/Departments and Institutions.  Our basic research has been supported by the Canadian Institutes of Health Research, the Alberta Heritage Foundation for Medical Research, the National Institutes of Health, the Alberta Diabetes Institute, and the Edmonton Civic Employees Charitable Assistance Fund.  The Juvenile Diabetes Research Foundation supports our clinical studies.

 

Tolerance Laboratory Staff/Students

William Chan (MMI PhD student; supported by studentships from the CDA and the MDRTC)


Dr. Wayne Truong (Experimental Surgery PhD student)

 

Shaheed Merani (Experimental Surgery PhD student)

 

Govindarajan Thangavelu (Experimental Surgery PhD student)

 

Dr. Juliet Emamaullee (PDF)

 

Haide Razavy (Technician)


Rena Pawlick (Technician)


Colleen Belohorec (Technician)

 

Joy Davis (Technician)

 

Ryan Edgar (Technician)


Carl Tan (Experimental Surgery MSc student)

 

Jennifer Plester (MMI MSc student)

 

Michael Bui (499 student)

 

Kristy Baron (499 student)

 

Tracy Mah (summer student)

 

Laura Stanton (summer student)

 

 

 

Selected Publications:

 

 

*Luo, B., *Chan, W.F.N., Lord, S.J., Nanji, S.A., Rajotte, R.V., Shapiro, A.M.J., and Anderson, C.C. (2006). Diabetes induces rapid suppression of adaptive immunity followed by homeostatic T-cell proliferation. Scand. J. Immunol. In press.  *co-first authors.

 

Nanji, S.A., Hancock, W.W., Luo, B., Schur, C.D., Pawlick, R.L., Zhu, L.F., Anderson, C.C., and Shapiro A.M.J. (2006). Combined ICOS and CD40L costimulation blockade induces dominant tolerance to islet allografts and prevents spontaneous autoimmune diabetes in NOD mice. Diabetes, 55, 27-33.

 

Anderson, C.C. (2006). Time, space and contextual models of the immunity tolerance decision: Bridging the geographical divide of Zinkernagel and Hengartner’s ‘Credo 2004’.  Scand. J. Immunol., 63, 249-256.

 

Merani, S., Truong, W.W., Hancock, W., Anderson, C.C., Shapiro, A.M. (2006)

Chemokines and their receptors in islet allograft rejection and as targets for tolerance induction. Cell Transplant.15, 295-309.

 

Truong, W., Hancock, W.W., Anderson, C.C., Merani, S., Shapiro, A.M. (2006)

Coinhibitory T-cell signaling in islet allograft rejection and tolerance.

Cell Transplant.15, 105-19.

 

Luo B., Nanji, S.A., Schur, C.D., Pawlick, R.L., Anderson, C.C., and Shapiro, A.M.J. (2005). Robust tolerance to fully allogeneic islet transplants achieved by chimerism with minimal conditioning. Transplantation, 80, 370-377.

 

Goldman, K.P., Park, C.-S., Kim, M., Matzinger, P., and Anderson, C.C. (2005). Thymic cortical epithelium induces self tolerance.  Eur. J. Immunol., 35, 709-717.

 

Anderson, C.C. and Chan, W.F.N. (2004). Mechanisms and models of peripheral CD4 T cell tolerance. Front. Biosci., 9, 2947-2963.

 

Nanji S.A., Hancock W.W., Anderson C.C., Adams A.B., Luo B., Schur C.D., Pawlick R.L., Wong L., Coyle A.J., Larsen C.P. and Shapiro A.M.J. (2004). Multiple combination therapies involving blockade of ICOS/B7RP-1 costimulation facilitate long-term islet allograft survival. Am. J. Transplant., 4, 526-536.

 

Anderson, C.C. (2004).  Conceptual Models In Immunity/Tolerance:  Application to transplantation.  Immunobiology of Organ Transplantation, edited by Burlingham, W. J. and Wilkes, D. S., Kluwer Academic/ Plenum Publishers. 171-190.

 

Anderson, C.C., Carroll, J.M., Gallucci, S., Ridge, J.P., Cheever, A., and Matzinger, P. (2001).  Testing Time-, Ignorance-, and Danger-based Models of Tolerance.  J. Immunol. 166, 3663-3671.

 

Anderson, C.C., and Matzinger, P. (2001). Tolerance or Immunity: Opposite outcomes of microchimerism from skin-grafts.  Nature Med., 7, 80-87. See also- Editorial pp 24-25.

 

 

Key Words:

 

Immunology, tolerance, transplantation, autoimmunity, islets of Langerhans

 

Telephone: (780) 492-6036

Fax: (780) 492-1627

E-mail: colinand@ualberta.ca