Research Faculty

Address
ICRC Room 1001
1130 St. Nicholas Ave
New York NY 10032

Phone: 212-851-4632
Fax: 212-305-4548

pc561@columbia.edu
Education and Training
Sc.B., 1987 Brown University
Ph.D., 1997 New York University School of Medicine
M.D., 1998 New York University School of Medicine
Peter D. Canoll, M.D., Ph.D.
Associate Professor of Pathology & Cell Biology
Research Summary

Diffusely infiltrating gliomas, including glioblastomas, astrocytomas, and oligodendrogliomas, are the most common type of adult brain tumors. Which cell types give rise to gliomas is not clear and identifying the 'cells of origin' remains a major goal of brain tumor research. To address this question, we have chosen to focus on the population of progenitors cells that reside in the adult white matter. The subcortical white matter is the largest region of the human forebrain and the most common location in which gliomas arise. Previous studies have shown that approximately 2% of the total cells in the adult rat white matter are cycling progenitors. In humans the number may be as high as 4%. Thus, white matter contains one of the largest pools of proliferating cells in the adult brain. Normally, these cells are slowly proliferating and non-migratory. However, when these cells are stimulated with certain growth factors, such as PDGF, they acquire a more proliferative and migratory phenotype that resembles glioma cells. Also, human gliomas express a number of proteins that are normally expressed by adult white matter progenitors, such as Olig2, NG2 and PDGFR⎕, suggesting they are closely related.

We have developed an experimental glioma model that uses a retrovirus to deliver PDGF and fluorescent reporter genes into adult rat white matter. Tumors that closely resemble human glioblastomas form in 100% of the animals injected. Remarkably, the tumors are composed of a mixture of progenitors infected with the PDGF retrovirus and non-infected progenitors that have been recruited via paracrine growth factor signaling. Both cell populations look and behave like malignant glioma cells. However, when the recruited progenitors are removed from the mitogenic environment they stop proliferating and differentiate. These findings raise several important questions about the relationship between glioma cells and adult progenitors. They also call into question 2 basic doctrines of cancer biology; 1) that tumors are derived from clonal expansion of a single transformed cell and 2) that the malignant behavior requires the accumulation of multiple genetic lesions.

We are using a variety of experimental approaches to study the regulation of glioma cell migration and proliferation and to further investigate interactions between glioma cells and adult progenitor cells in the PDGF model. Our approaches include time-lapse microscopy to monitor migration and proliferation of GFP and DsRed labeled cells in living slices of brain; isolation of progenitor cells and glioma cells from the rodent model and from human tumor specimens using FACS; analysis of proliferation, differentiation, migration and survival in vitro; immunohistochemistry, in situ hybridization and microarray analysis to compare the alterations of gene expression that occur in the PDGF model and those seen in human glioblastomas. In collaboration with the Laboratory of Dr. Jeffery Bruce, we are using the PDGF retrovirus model to test the efficacy of intracerebral delivery of chemotherapeutics.

Selected Publications

Please click the PubMed link below to view Dr. Canoll's publications:

Honors and Awards

1996
Merck Scholar

1998
Award for Distinguished Performance in Research, Associated Medical Schools of New York

2001
Inspiration Award for Pediatric Brain Tumor Research, Children's Brain Tumor Foundation

2002
Sontag Foundation Award for Brain Tumor Research, American Brain Tumor Association

2008
Teacher of the year award for outstanding small group preceptor

2009
Adult Translational Award, Society for Neuro-oncology


Committees , Council, and Professional Society Memberships

Society for Neuroscience

Society of Neurooncology


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