Full Professor and Director of the Cancer and Genetic Diseases Division Montreal Clinical Research Institute (IRCM)
Thursday, 22 June 2017 at 4:00 pm in QCRI Conference Rooms 100/01
“UNRAVELLING THE COMPLEXITY OF METASTASIS”: Characterizing the roles of the receptor tyrosine kinase AXL in metastatic progression
The majority of breast cancer deaths occur as a result of the formation of metastases. The metastatic process is complex: cancer cells must acquire invasive properties to migrate through the blood vessels to ultimately reach and survive at secondary sites. The expression of AXL correlates with the formation of metastases in several types of cancers, but the mechanism by which AXL plays its pro-metastatic function is poorly understood. We used proteomics approaches (phospho-MS and BioID screens) to identify signalling networks controlled by AXL. We also used in vivo approaches using mouse models and human Patient-Derived Xenografts to determine the involvement of this RTK at multiple stages of the metastatic process. Our results suggest that inhibition of AXL would be beneficial in limiting the spread of breast cancer.
Laval University and CHU-Q Hospital Research Centre, Quebec City, QC
Monday, 26 June 2017 at 12:00 noon in QCRI Conference Rooms 100/01
“Expanding roles of PARP1 in DNA-damage responses and its implication for cancer therapy"
After 50 years of discovery of poly(ADP-ribose) polymerase (PARP) metabolism, we are still identifying novel physiological and stress-related responses of PARP1, the principle enzyme of PARP metabolism. PARP1 is among the first proteins in mammalian cells to reach the DNA lesions, and gets activated to form polymers of ADP-ribose (PAR) that post-translationally modify target proteins. Prof Shah’s team has been exploring consequences of PARP-1 activation and PARylation of target proteins at the site of different types of DNA lesions in different processes ranging from DNA repair to cell death and cancer. He will discuss recently identified roles of PARP1 in cellular responses to UV-damaged DNA, including the nucleotide excision repair pathway (1), and non-homologous end joining repair (2). Professor Shah’s team has recently developed SKH-1 albino hairless PARP1-knockout mice as a model to study the roles of PARP1 in solar UV-induced non-melanoma skin cancers. Lastly, he will discuss how the pharmacological inhibitors of PARP1 have the potential to offer novel therapeutic approaches for treatment of not only BRCA-mutant breast and ovarian cancers (3,4), but also other cancers and non-cancer pathologies associated with PARP metabolism.
Hosts: Drs. Lois Mulligan (firstname.lastname@example.org) and Peter Greer (email@example.com)
Dr. Sirin Adham (Sultan Qaboos University, Muscat, Oman)
Thursday 17 Aug/17 at 4:00 pm in QCRI Conf Rms 100/10
"Investigating Specific Molecular Targets for Triple Negative Breast Cancer in Clinical Samples"
Circulating plasma and peripheral blood mononuclear (PBMCs) cells provide an informative snapshot of the systemic physiological state. The role of Neuropilin-1 (NRP-1) and its interacting molecules in breast cancer was associated with progression. We found that circulating and tumor tissue expression of NRP-1 and circulating placental growth factor (PlGF) were upregulated in triple negative breast cancer (TNBC) compared to other subtypes. In PBMCs VEGFR3 and PLXNA1 expression can differentiate between TNBC and non-TNBC tumor subtypes. This work supports the importance of NRP-1-associated molecules in circulation to characterize poor prognosis breast cancer and emphasizes on their role as favorable drug targets.