Dr. Moulay Alaoui-Jamali
Departments of Medicine and Oncology, McGill University
FRSQ Research Scholar
Associate Member, Goodman Cancer Research Centre
Changes in the local tumor microenvironment play an essential role in the development and progression of cancer. Using cellular and genetic approaches, this laboratory has demonstrated that specific members of the ErbB and non-ErbB tyrosine kinase receptor family play a key role in the regulation of tissue microenvironment and tissue homeostasis via multiple autocrine and paracrine signaling loops. These loops promote the disorganization and disassembly of the extracellular matrix, activation of local host stroma, and neovascularization. We are currently pursuing genomic and functional proteomic studies in order to understand these mechanisms, and determine their implications for cancer. A second aspect of our research is to characterize the function of a novel cancer associated gene we named p22RBT1. p22RBT1 is a nuclear protein that plays a role in the regulation of cell cycle and acts as a potent transcriptional co-activator. Furthermore, overexpression of this protein in normal cells leads to cellular transformation and tumor formation. We are pursuing genetic studies in cell lines and knockout mice to examine the function of this protein and its partners in transcription, cell cycle and carcinogenesis. A third aspect of our research is to understand the mechanisms by which viral oncoproteins, such as those of hepatitis B/C viruses, and their associated inflammatory processes, enhance cell susceptibility to carcinogenesis. We demonstrated that HBV/HCV enhance cell susceptibility to site-specific mutagenesis by interfering with DNA repair and its associated cell cycle checkpoints. The molecular mechanisms involved are under investigation. Finally, this laboratory has established a recognized expertise in in vivo models to study the anticancer, antimetastatic and antiangiogenic activities of novel agents. These models are now being used for drug/target discovery.