Dr. Gil Mor Professor and Director Division of Reproductive Sciences Director, Discovery to Cure Translational Research Program Department of obstetrics, Gynecology & Reproductive Sciences Yale University School of Medicine
Cancer stem cells: implications for chemoresistance and recurrence
A major burden in the treatment of ovarian cancer is the high percentage of recurrence and chemoresistance. Cancer stem cells (CSCs), provides a reservoir of cells that can self-renew, maintain the tumor by generating differentiated cells (non-stem cells (non-CSCs)) which make up the bulk of the tumor and may be the primary source of recurrence. We describe the characterization of human ovarian cancer stem cells (OCSCs). These cells have a distinctive genetic profile that confers them with the capacity to recapitulate the original tumor, proliferate with chemotherapy, and promote recurrence. Chemotherapy eliminates the bulk of the tumor but it leaves a core of cancer cells with high capacity for repair and renewal. The molecular properties identified in these cells may explain some of the unique characteristics of CSCs that control self-renewal and drive metastasis. The identification and cloning of human OCSCs can aid in the development of better therapeutic approaches for ovarian cancer patients.
April 25th, 2018 1:00 - 2:00pm Biosciences Complet, Room 1102
Canada Research Chair Senior Investigator & Professor Departments of Molecular Genetics and Laboratory Medicine and Pathology Lunenfeld-Tanenbaum Research Institute Mount Sinai Hospital Toronto, Ontario
N-glycosylation and metabolism: a critical network in cancer progression
Metabolic reprograming in cancer cells increases the flux of glucose into anabolic pathways including the Hexosamine Biosynthesis Pathway (HBP) which supplies UDP-GlcNAc to N-glycan branching. We have shown that loss-of-function in these pathways suppresses cancer progression, alters T cell regulation and risk of autoimmune disease, and plays a role in glucose homeostasis. The branching and elongation of N-glycan chains found on cell surface receptors generates a gradation of affinities for carbohydrate-binding proteins, the galectin, selectin and siglec families. These interactions adapt cellular responsiveness to environmental conditions. Attesting to their importance, glycoproteins display accelerated evolution rates proportional to N-glycosylation site multiplicity during vertebrate radiation. Complex polygenetic diseases involve multiple pathways, and effective treatments are likely to require a better knowledge of gene interactions (SIs). The advent of CRISPR/Cas9 gene editing makes discovery of gene interactions possible on large scale. However, this is a large challenge that requires the collaboration of many research groups. I will discuss the background on our work with HBP and N-glycan branching pathways, and our progress on genome-wide CRISPR/Cas9 screening in query tumor cell lines with specific mutations targeting HBP and N-glycan branching enzymes.
Wednesday, May 2nd, 2018 10:00 - 11:00 am Botterell Hall, Room B139
Immunotherapy: learning how to turn up the heat on cold tumors
Immunotherapy has made a big impact in clinical oncology in the last 5 years however this clinical activity is only seen in the minority of tumors that already are recognized by the immune system (either due to neoantigens or viral antigens) and have an active but stalled immune response. Several techniques are showing promise in combination with immune checkpoint inhibition that may broaden the activity of immunotherapy to the majority of tumors that aren't recognized by the patient's immune system. Dr. Gulley will discuss some of these approaches his group is testing in the clinic and share emerging data as well as techniques to evaluate the impact of immunotherapy on the tumor microenvironment.