A gift from BRIGIL led to the identification of genes involved in the predisposition to colitis-induced colorectal cancer
Mr. Gilles Desjardins, president and CEO of a Gatineau construction company named BRIGIL decided to offer a substantial gift to the research team headed by Drs. Nicole Beauchemin and Philippe Gros to pursue their work on the identification of colorectal cancer (CRC) genes that predispose patients to the development of this cancer. This gift complemented a grant obtained and renewed from the Cancer Research Society.
The Morris and Rosalind Goodman Family Foundation has made a generous gift that will support a Chair to attract a world-class scholar who will make major contributions to the study of cancer, with emphasis on pulmonary cancer. In addition, their donation will help train young researchers to lead tomorrow’s cancer breakthroughs.
The Role of the Novel Multi-Argonaute Interacting Protein NIP-1 in Inheritable Nuclear RNAi
RNA interference (RNAi) is an umbrella term for highly conserved gene silencing mechanisms initiated by small, double-stranded RNA molecules. First discovered in plants, RNAi revolutionized the field of molecular biology. Doublestranded RNA (dsRNA) with sequence complementarity to a gene will lead to knockdown of that gene’s protein product, making it a novel research tool with possible applications in therapeutics. In short, long double-stranded RNA substrates are processed into shorter molecules called small interfering RNAs, or siRNAs, and loaded into proteins called Argonautes, which make up the heart of the protein complexes that execute gene silencing. This silencing phenomenon is not unique to synthetically introduced dsRNA. Recent studies have implicated endogenous RNAi mechanisms in development, fertility, and maintenance of chromatin (the combination of DNA and proteins that make up our chromosomes).
The proposed project will focus on characterizing the role of a novel protein (NIP-1) that was found to interact with several Argonautes in C. elegans. We believe it may play a role in stabilizing or loading the Argonaute silencing complexes with siRNAs. I will determine the function of this protein using several validated functional RNAi assays and establish the network of other proteins that interact with NIP-1. Very little is known about the mechanisms that make up these endogenous pathways and it is our hope that the following project will contribute to our understanding of RNAi. Understanding RNAi at the molecular level is crucial, because as new functions for RNAi pathways emerge in C.elegans and other organisms, so do the number of ways they can be misregulated in states of disease.
Alexander Kiepas, M.Sc. - Canderel Studentship Award, 2015
Role of Lipoma Preferred Partner (LPP) protein in breast cancer cell migration, invasion, and metastasis
Canadian women face a 1 in 9 risk of developing breast cancer throughout their lifetime. Despite significant progress in detection and early treatment, metastatic breast cancer capable of spreading to distant organs and tissues is largely incurable. A clearer understanding of the mechanisms controlling cell migration from the primary tumor into distant tissues is needed to identify new therapeutic targets.
Previous work by our group has identified Lipoma Preferred Partner (LPP) protein as a critical regulator of migration, invasion and metastasis in breast cancer cells by virtue of its ability to control the dynamics of adhesions that anchor the cell to its surrounding environment. My goals are to determine (1) how LPP is recruited to adhesions, (2) how LPP regulates the formation, stability and disassembly of these structures, and (3) if LPP acts as a force transducer to help breast cancer cells sense the stiffness of the substrates they migrate on.
Cancer research has always been a subject very close to my heart. My great grandmother died of breast cancer, my grandmother had a tumor removed, and my mother undergoes annual monitoring for suspicious lesions. The results of the present study have the potential to identify a new biomarker and therapeutic target in metastatic breast cancer. We will determine, for the first time, whether metastasis is drive by substrate stiffness. New strategies may then be developed to diminish the aggressiveness of this lethal form of cancer and improve clinical outcomes for patients.
Amr Omer Department of Biochemistry Masters Student Laboratory of Dr. Imed Gallouzi
Post-transcriptional Regulation of Interleukin-6 and -8 is a Key Mediator of Senescence
My project consists of studying the relationship between the changes in the expression of certain genes and the development of cancer with aging. It has been established that with age, a certain number of cells stop dividing (through a process known as "senescence") and accumulate in various tissues. This accumulation leads to the secretion of senescence associated secretory phenotype (SASP) factors, which promote the transformation of neighboring cells and metastasis.
Preliminary results indicate that post-transcriptional events are involved in the aberrant production of these factors, the details of the regulation process and the factors involved are not known. My project is to determine how messenger RNAs encoding these factors are regulated by associating proteins, which bind to these messages at the post-transcriptional level and the role of this regulation on the development of cancer and accumulation of senescent cells in elderly patients.
Jin Yong Patrick Park Canderel Studentship Award 2015 MSc in Experimental Medicine Laboratory of Dr. George Zogopoulos
Characterization of Pancreatic Adenocarcinoma Associated with Germline Homologous Recombination DNA Repair Defects
Pancreatic Adenocarcinoma (PC) is a deadly malignancy, and it is the fourth leading cause of cancer deaths in Canada. Unfortunately, the overall 5-year survival rate of this disease still remains at only 6 percent. PC being a genetically and molecularly heterogeneous disease is one of the reasons for this poor prognosis. Patients often show varying responses to currently available systemic chemotherapies, and thus there is strong motivation to evaluate novel therapies that target specific subtypes of PC.
In this project, I will characterize PC cases associated with germline mutations in genes involved in homology-directed DNA repair (HDR), and evaluate BMN 673, a novel PARP inhibitor, which may serve as a precision therapy for patients with this subtype of PC. In addition, I hope to identify a novel molecular signature that may serve as a prognostic tool for PC cases that will benefit from therapeutic strategies that exploit HDR defects.
My strong interest and motivation toward my project arise primarily from the significant translational impact that the findings may have. In fact, the findings from my project will help rationalize future clinical trials for HDR-associated PC.
Shivshankari Rajkumar Canderel Studentship Award 2015 MSc in Biochemistry Laboratory of Dr. Ian Watson
Identifying novel therapeutic strategies for the treatment of NF1 mutant melanomas
Cutaneous melanoma is the deadliest form of skin cancer that originates in melanocytes, the pigment producing cells of the skin. Current targeted therapeutic options rarely provide patients with a durable anti-tumour response due to the development of resistance. By elucidating the role of NF1, a significantly mutated tumor suppressor gene, in melanomagenesis, we hope to develop novel therapeutic strategies for the treatment of patients harboring mutant NF1 melanomas.
My interest in cancer research stems from my past undergraduate research experience characterizing the glycoprotein, Pannexin-3 in rhabdomyosarcoma (RMS), a sarcoma that afflicts children and adolescents. I am highly interested in research involved in understanding the molecular mechanisms underlying cancer processes by applying current state-of the art biochemical and molecular biology techniques. Namely, I am especially keen on incorporating the use of “OMIC” approaches to examine changes in genes, proteins and metabolites in cancer cells compared to normal cells. This will allow us to intervene in key pathways of the disease process to reduce cancer cell proliferation and induce death of these cells. Ultimately, this will pave way to the development of novel therapeutic approaches that can overcome the hurdle of drug resistance and can lead to enhanced survival of melanoma patients.
Arresten Production in Tumour Growth Arrest and Cancer Diagnosis
Tumour cells can release factors that promote the generation of new blood vessels which allows greater access to oxygen and nutrients. This creates an environment that permits tumours to grow. The human body suppresses tumour growth by releasing anti-angiogenic factors into the blood stream to inhibit the formation of these blood vessels.
An anti-angiogenic factor called Arresten is an endogenous angiogenesis inhibitor that is upregulated by the p53 tumour suppressor. By gaining further understanding on the way Arresten is processed, we can determine how to suppress tumour growth. We hypothesize that Arresten levels in circulation play an important role in tumour suppression and have the potential to be used both for cancer diagnosis and treatment.
Therefore, we will focus on identifying the proteases that are involved in cleaving Arresten from the extracellular matrix of human cells. We will also characterize the levels of Arresten in the blood of patients and determine if there is a correlation between Arresten levels and the prevalence of cancer. In addition to having great potential as a diagnostic tool for cancer, Arresten can easily be translated as a novel therapy for inhibiting angiogenesis and tumour growth, since it is naturally produced in humans.
Fatemeh Fekrmandi, M.D., M.Sc. - MICRTP Travel Award 2015
Anticancer and anti-inflammatory effects of vitamin D
Our project examined the molecular basis for the anticancer properties of vitamin D. We did this by studying the interaction of the vitamin D cell receptor with an enzyme, the E3 ligase FBW7. FBW7 targets turnover of several proteins, many of which are oncogenes, that is, they play an important role in cancer development. One of these is nuclear factor kappa B (NF-B), whose signaling controls inflammatory immune responses, and is often altered in human cancer. I successfully showed that vitamin D suppresses different NF-B subunits in different cancer cell lines by stimulating its FBW7-mediated turnover. The results of this work were recently accepted for publication as an original paper in Nature Publishing Group (July 2015).
Étienne Audet-Walsh, Ph.D. - MICRTP Travel Award 2015
Presenting a new cell-signaling pathway that can potentially improve the use of antifolates in cancer therapy
The MICRTP Travel Award offers great opportunities for students and postdoctoral fellows. As a part of this program, I will be able to present my work exploring a new cell-signaling pathway that can potentially improve the use of antifolates in cancer therapy at an important meeting in France in September 2015. The results that I will present show that the PGC-1a/ERRa axis, a powerful cell signaling pathway, can control the activity of genes involved in One-Carbon Metabolism, a pathway which is used by cancer cells to grow faster.
Oraly Sanchez Ferraz, Ph.D. - MICRTP Travel Award 2015
Deciphering the molecular regulators of collective cell migration in a model of tissue invasion
Collective cell migration (CCM) is an important mechanism for metastatic invasion and migration of epithelial cancers. However, how CCM is orchestrated at the molecular level is still poorly understood and the targeting of this process hampered by the limited number of in vivo models of CCM. A powerful and tractable model of CCM occurs during the elongation of an epithelial tube known as the nephric duct (ND), during embryonic development. My research project aims to use the ND elongation process as a model of CCM in development and tumor invasion. For this I will use powerful tools such as live imaging and mouse genetics, particularly the CRISPR/Cas9 genome editing technology. With my expertise in embryology and mouse genetics, the guidance of Dr. Bouchard an expert in the fields of mouse genetics; development and cancer of the urogenital system, the platforms and fertile scientific environment of the GCRC and the financial support of the MICRTP program, this project will identify new molecules and pathways implicated in tumor invasion that can be used as therapeutic targets for cancer.
Li-Ting Wang - MICRTP Travel Award 2015
Gaining comprehensive training and scientific knowledge
The McGill Integrated Cancer Research Training Program (MICRTP) will allow me to communicate with people from multiple disciplines and institutes, and exchange ideas through workshops and meetings. This program provides the tools to gain comprehensive training and scientific knowledge to yield answers to my area of research. I will do my best to research cancer prevention and treatment, and hope to address issues plaguing cancer researchers to provide a potential solution for practical application.