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.
Dr. Joyce Ohm (Assoc. Professor of Oncology, Roswell Park Cancer Institute)
Thursday 14 Sept/17 at 4:00 pm in QCRI Conf Rms 100/10
"Genetic and Environmental Reprogramming of the Cancer Epigenome"
Dr. Joyce Ohm is an Associate Professor of Oncology at the Roswell Park Cancer Institute in Buffalo, NY. Her highly cited research program investigates mechanisms behind epigenomic plasticity and how plasticity contributes to tumor initiation and progression. She is interested in how both genetic driver mutations and environmental toxicant exposures can reprogram the epigenome, increasing stemness and contributing to cancer progression. Using -omics level approaches, her team studies transcriptome (RNA-sequencing), methylome (Illumina EPIC DNA methylation arrays), and global chromatin changes (ATAC-sequencing) in normal, pre-malignant, and malignant cell populations in response to genetic and environmental insults. The work is aimed at identifying novel therapeutic strategies for the treatment of aggressive human cancers based on their molecular profiling and to determine whether epigenetic therapies are effective at augmenting standard of care for specific subsets of patients.
Axel Thomson, PhD (Assoc. Professor, McGill University, Dept. of Surgery, Division of Urology, and Cancer Research Program)
Thursday 16 Nov/17 at 4:00 pm in QCRI Conf Rms 100/01
"Stromal regulation of prostate development and cancer; using tissues and single cell transcriptomics to define new markers and mechanisms"
Dr Thomson has spent his career studying how androgens and stromal:epithelial interactions control prostate growth in both development and cancer. This has involved transcriptional profiling of developmental mesenchyme and cancer-associated fibroblasts with tissue and single cell methods, and using models with low cell and tissue heterogeneity – a major confounder in biology and transcriptomics. Androgen signalling within mesenchyme is essential for the development of male sex-accessory organs such as the prostate, while androgen action in tumour stroma contributes to prostate tumourigenesis and progression. Most studies of androgen action have focussed upon Androgen Receptor function in tumour and epithelial cells, but Dr Thomson has addressed androgen action in stroma. Similarly, predictive bio-marker research has focussed on tumour cells, though stromal markers have emerged as a new way to predict cancer outcome. Mis-expression of developmental mesenchymal pathways in tumour fibroblasts has been shown to reduce tumour growth and invasion, confirming the importance of stroma in tumour progression.
Dr Thomson has lost many battles with prevarication, self-discipline, reviewers, and his children. He has ridden many technology bandwagons, and considers himself a reasonable judge of over-hyped claims, excluding his own. His seminar features old and modern methods, plenty of physiological relevance, and a minimum of statistics. The talk will be delivered with enthusiasm; perhaps sufficient to keep both senior faculty and students awake, for at least some of it. Dr Thomson will consider the talk a success if he is not chased out of the auditorium, and any of those in the audience can remember any part of the data or conclusions one month later.
Sheela Abraham, PhD Asst. Professor, Dept. of Biological & Molecular Sciences, Queen's University
Thursday 25 January 2018 at 1:30 pm*
QCRI 100/01 conference rooms
Title: "Investigating Signalling Pathways in Normal and Cancer Haematopoietic Stem Cells"
Chronic myeloid leukaemia (CML) is a clonal disorder, initiated by the expression of the BCR-ABL1 oncogene. Most CML patients must take tyrosine kinase inhibitors (TKIs) such as imatinib mesylate indefinitely, thus TKIs represent a life-long treatment without providing true cure. Our group identified that in CML the existing residual disease resistant to TKIs, is comprised of leukemic stem cells. To investigate the biology behind this critical tumour-initiating and maintaining subpopulation, we conducted systems approaches providing deeper insight into CML and importantly, engineered a more fundamental synthetic lethality proving superior to single target approaches. Our work has added to the knowledge base surrounding intracellular-based signalling events in leukaemia. In this seminar, I will present previous and future studies that incorporate our ‘OMICS’ approach focused on delineating critical pathways involved in normal and cancer stem cell maintenance.
Host: Dr. Andrew Craig (firstname.lastname@example.org)
*1:00pm - Welcome reception for Dr. Abraham, a new recruit in DBMS and Cancer Biology & Genetics division. Please join us for some refreshments (coffee, tea, cookies) and socialize prior to the seminar.
Douglas Richardson, PhD Director of Imaing, Lecturer on Molecular and Cellular Biology Harvard Center for Biological Imagining (Harvard University)
Tuesday 20 Feb/18 at 2:00 pm in QCRI 100/01 conference roms
"Measuring endosomal pH beyond the diffraction limit"
Fluorescence-based biosensors have become essential tools for modern biology, allowing real-time monitoring of biological processes within living cells. One widely used application of biosensors is to monitor the acidification of vesicles during endocytosis, an essential function that aids in intracellular cargo sorting and degradation. Prior to the development of super-resolution fluorescence microscopy (nanoscopy), investigation of endosomal dynamics in live cells remained difficult as these structures lie at or below the ~250 nm diffraction limit of light microscopy. Therefore, to aid in investigations of pH dynamics during endocytosis at the nanoscale, we have specifically designed a family of ratiometric endosomal pH probes for use in live-cell STED nanoscopy.
Thursday 01 March 2018 at 4:00 pm in QCRI 100/01 conf. rms.
Connie Zhang, PhD Senior Technical Support Scientist Advanced Cell Diagnostics, Newark, CA
"Visualizing gene expression and genetic variations in the tissue environment"
The RNAscope® technology is an advanced in situ hybridization platform that allows for the visualization of single-cell gene expression, targeting mRNA and ncRNA sequences directly in tissues. This highly sensitive and specific approach permits the detection of biomarkers in both the tumor and stroma, as well as secreted molecules, such as cytokines and chemokines. In this seminar we will examine applications of the RNAscope assay in oncology and immuno-oncology.