|Dr. David DANKORT|
David Dankort received his PhD in Biology from McMaster University, where he biochemically and genetically dissected the oncogenic signals emanating from the ErbB2/Neu receptor tyrosine kinase (RTK). As a research assistant in the same lab he generated several ErbB2 transgenic models of breast cancer and uncovered a metastatic specific pathway from the ErbB2 RTK. He then went on to develop sophisticated genetically engineered mouse models of lung cancer and melanoma as a General Motors Cancer Research Postdoctoral Fellow in Martin McMahon’s lab at the UCSF Comprehensive Cancer Center. Dr. Dankort joined the Department of Biology at McGill as Assistant Professor in November 2008. As a member of the DBRI, he is using genetically engineered mouse models to study cell growth control and metastasis in a whole organism.
Genetically engineered mice are presently the gold standard for whole organism cancer modeling. Existing and emerging technologies afford researchers the ability to query fundamental questions regarding the genetics of tumor initiation, progression, maintenance and ultimately, malignancy.
Cancer arises due to the sequential acquisition of genetic and epigenetic “hits” in a stepwise fashion. The genes can be loosely grouped into two classes: oncogenes and tumour suppressor. RAS and BRAF are the two most prevalent mutated oncogenes found in human cancers, particularly in lung cancer (~30%) and melanoma (~85%) where they function in the classical Ras-activated Raf-Mek-Erk kinase pathway. Additionally, there is a constellation of tumour suppressor loss in these cancers particularly losses in p53, PTEN, and INK4a/ARF. Despite the enumeration of genetic lesions from human cancer data, there is a lack of understanding of how these oncogenes and tumour suppressors contribute in the evolution of malignancy. For instance, aberrant activation of the Ras-activated Raf-Mek-Erk pathway in primary cells paradoxically induces a sustained cell cycle arrest (senescence), suggesting additional genes cooperate to permit tumour formation and/or progression. Armed with the vast array of genetic and molecular tools afforded to those who work with the mouse as a model organism, the Dankort lab seeks to: define these cooperating genes and how they function, establish when they are important in the evolution of a tumour and to determine the proper cell to target for destruction within a tumor. The results of these findings will be important for the understanding of aberrant cell control and tumour progression and will inform the development of rational therapeutic strategies to treat effectively cancer.
Dankort D, Curley D, Cartlidge R, Nelson B, Karnezis A, Damsky W, You, M, DePinho R, McMahon M and M Bosenberg. (2009) BRafV600E cooperates with Pten loss to induce metastatic melanoma. Nature Genetics [Published online: 12 March 2009 | doi:10.1038/ng.356]
Dankort D, Curley D, Cartlidge R, Nelson B, Karnezis A, Damsky W, You, M, DePinho R, McMahon M and M Bosenberg. (2009) BRafV600E expression combined with Pten silencing cooperate to induce metastatic melanoma Nature Genetics (in press)
Dankort D, D Curley, X Zhang, R DePinho, M McMahon and M Bosenberg. (2009) BRafV600E expression combined with Pten silencing cooperate to induce metastatic melanoma Nature Genetics (Revised manuscript under review NG-A23700R)
Dankort, DL, Z Wang, V Blackmore, MF Moran and WJ Muller (1997) Distinct tyrosine autophosphorylation sites negatively and positively modulate Neu-mediated transformation Mol Cell Biol 17(9): 5410-5425.