Professor, Department of Biochemistry
Tumour Angiogenesis and Apoptosis
Rosalind and Morris Goodman Cancer Center and
Department of Biochemistry
The Cancer Research Building
1160 Pine Avenue
Office: Room 616; Lab: Room 607
Montreal, Quebec H3A 1A4
Tel: 514-398-3273; Lab: 514-398-8934
Fax: 514-398-6769
jose.teodoro [at] mcgill.ca
1994 - PhD, Ï㽶ÊÓƵ
Major Awards
- 2000-2003 The Medical Foundation Charles A. King Trust Fellowship
- 1997-2000 National Cancer Institute of Canada Postdoctoral Fellowship
- 1997 Prix d’Excellence de l’Académie des Grands Montréalais
- 1997 Governor General’s Gold Medal
- 1994-1996 National Cancer Institute of Canada, Steve Fonyo Research Studentship
Research Interests
My lab has a broad interest in identifying molecular pathways that limit tumour growth and delineating the mechanisms by which they become subverted in cancer. Towards this goal, we are studying two distinct processes.
A. The Role of the p53 Tumour Suppressor in Inhibiting Angiogenesis.
Angiogenesis, the process by which new blood vessels are formed, is an absolute requirement for tumour formation. One of our interests is understanding how tumors become vascularized and the mechanisms that can limit this process. Our focus is on the p53 tumour suppressor pathway and how it is able to inhibit angiogenesis. The p53 gene is mutated in half of all human cancers and at least part of its tumour suppression activity stems from inhibiting tumour vascularization. Angiogenesis is regulated through a balance of factors that either promote or inhibit vascularization. Studies from our group demonstrated that p53 stimulates the production of the potent angiogenesis inhibitors Endostatin and Tumstatin. Projects in the lab include the identification of novel p53-induced angiogenesis inhibitors and defining how such factors work.
B. Viral Mechanisms of Tumour Cell Destruction.
A variety of animal viruses have the ability to kill cancer cells while leaving normal cells unaffected. Thus, discovering the mechanisms by which these viruses destroy cancer cells could potentially lead to novel pathways that can be exploited for therapy. We use the viral protein Apoptin from Chicken Anemia Virus as a model for understanding tumour-specific cell death. The Apoptin protein has the ability to induce cell cycle arrest and p53-independent apoptosis specifically in cancer cells. We demonstrated that Apoptin interacts with and inhibits a large protein complex called the Anaphase Promoting Complex/Cyclosome (APC/C). The APC/C is absolutely required for cells to progress through mitosis and been shown to be a cellular target of several human viruses including HTLV, Adenovirus and Papillomavirus. Projects in the lab seek to determine why the APC/C seems to be a general target of such a diverse range of viruses and how inhibition of this complex can lead to specific destruction of cancer cells.
Selected Publications
(2006). p53-Mediated Inhibition of Angiogenesis through Upregulation of a Collagen Prolyl Hydroxylase. Science 313; 968-971.
(2006) Apoptin Nucleo-Cytoplasmic Shuttling is Required for Cell-Type-Specific Localization, Apoptosis and Recruitment of APC/C to PML. Journal of Virology. 80; 7535-7545.
(2005) The Anaphase Promoting Complex: A Critical Target of Viral Proteins and Anti-Cancer Drugs. Cell Cycle 4; 560-563.
(2004). The viral protein Apoptin associates with the anaphase-promoting complex to induce G2/M arrest and apoptosis in the absence of p53. Genes & Development 18:1952-1957.
(2001) Induction of Apoptosis by a Secreted Lipocalin That Is Transcriptionally Regulated by IL-3 Deprivation. Science 293, 829-834.