CSB Seminar: Emergent cellular ecosystems in melanoma revealed by single cell analysis
“Emergent cellular ecosystems in melanoma revealed by single cell analysis”
Arjun Raj, Full Professor
University of Pennsylvania
Department of Bioengineering
Department of Genetics
Abstract:
Anti-cancer therapies can often kill the vast majority of tumor cells but a few rare cells remain and grow despite treatment. Non-genetic variability has emerged as a potential contributor to this behavior. However, it remains unclear what drives this variability, and what the ultimate phenotypic consequences are. We have developed a set of new single cell barcoding technologies (Rewind and FateMap) that have enabled us to show how different types of variability can translate into different drug-resistant outcomes upon treatment with drug. In particular, we found that even a genetically and epigenetically clonal population harbors enough latent variability to produce an entire ecosystem of different resistant cell types, and show preliminary evidence suggesting that these cell types can contribute to tumor development in distinct ways.
Friday, 12th, 2021 at 11:00am
https://utoronto.zoom.us/j/94049486250
Host: Student invited speaker (Steven Chen)
CSB Seminar: The evolutionary potential of the SARS-CoV-2 receptor binding domain
“The evolutionary potential of the SARS-CoV-2 receptor binding domain”
Jesse Bloom, Associate Professor,
Fred Hutchinson Cancer Research Center
Investigator, Howard Hughes Medical Institute
Abstract:
Hopes for ending the SARS-CoV-2 pandemic rely largely on vaccines that are designed to elicit neutralizing antibodies that target the viral spike. Here I describe my lab’s work to understand how these antibodies target the spike’s receptor-binding domain, and the potential for viral mutations to affect recognition by these antibodies.
Friday, Jan 29th, 2021 at 12:00pm
https://utoronto.zoom.us/j/94049486250
Host: Student invited speaker (Steven Chen)
CSB Seminar: Exploring the landscape of tumor invasion at single-cell resolution
“Exploring the landscape of tumor invasion at single-cell resolution”
Research Fellow Miranda Hunter
Memorial Sloan Kettering Cancer Center
Abstract:
When tumors invade into different tissues, they come into contact with new cell types within the tumor microenvironment, but it is unclear how tumor and microenvironment cells interact to facilitate tumor invasion. To understand how changes in gene expression in both the tumor and surrounding cells influence tumor invasion, we integrated spatial transcriptomics, single-cell RNA-seq, and in vivo confocal microscopy to characterize tumor-microenvironment cell-cell interactions in a transgenic zebrafish model of melanoma. Using spatial transcriptomics, we identified a unique “interface” cell state at the tumor/microenvironment boundary. Single-cell RNA-seq revealed that the interface is composed of specialized tumor and microenvironment cells that upregulate a common set of cilia genes. We further found that cilia proteins are polarized specifically where the tumor contacts the microenvironment, indicating a novel role for cilia in melanoma invasion. Motif analysis revealed that cilia gene expression in interface cells is regulated by ETS-family transcription factors, which normally act to suppress cilia genes outside of the interface. Finally, we found that an ETS/cilia-driven interface is conserved across ten patient samples, indicating that it is a conserved feature of human melanoma. We are currently investigating the molecular mechanisms by which cilia facilitate tumor progression. Our results uncover a previously unknown role for cilia in melanoma invasion, and the power of applying interdisciplinary approaches to understanding cancer cell biology.
Friday, Jan 15th, 2021 at 11:00 a.m.
https://utoronto.zoom.us/j/94049486250
Host: Rodrigo Fernandez-Gonzalez (rodrigo.fernandez.gonzalez@utoronto.ca)
CSB Seminar: Environmental epi/genetics in mammalian development and cancer
“Environmental epi/genetics in mammalian development and cancer”
Miguel Ramalho-Santos, Professor
Lunenfeld-Tanenbaum Research Institute
Abstract:
Friday, Dec 4th, 2020 at 11:00 a.m.
https://utoronto.zoom.us/j/94049486250
Host: John Calarco (john.calarco@utoronto.ca)
CSB Seminar: Signals, forces, and cells: Decoding tissue morphogenesis
“Signals, forces, and cells: Decoding tissue morphogenesis”
Jennifer Zallen,
HHMI/Sloan Kettering Institute
Abstract:
During development, cells move and reorganize in response to a wide range of signals to build the unique structures of different tissues in the animal. How these behaviors are systematically organized across hundreds of cells is a question that has long fascinated developmental biologists. We found that in the Drosophila embryo, the cell movements that elongate the head-to-tail body axis are regulated by a global positional code provided by an ancient family of Toll-related receptors that are widely used for pathogen recognition by the innate immune system. These receptors direct the localization of cellular force-generating proteins that drive cell intercalation and rosette formation, conserved cell behaviors that promote epithelial elongation in flies, chicks, frogs, worms, and mice. Recent work on how genes encode the forces that shape tissues, and how cells modulate their behavior in response to biochemical and mechanical changes in their environment, will be presented.
Friday, Feb 26th, 2020 at 11:00 a.m.
https://utoronto.zoom.us/j/94049486250
Host: Tony Harris (tony.harris@utoronto.ca)