Speaker: Karen Osei-Boamah

Title: “IronMΦ: A Model of Reticuloendothelial Macrophage Iron Metabolism”

Via Webex: https://uconnhealth.webex.com/uconnhealth/j.php?MTID=mdacf393cf6a2ee5314a3b76525ea5e57

Speaker: Maya Abdalla

Title: “Biomechanical modeling of spatiotemporal bacteria-phage competition”  

https://www.nature.com/articles/s42005-025-02078-1

Via Webex: https://uconnhealth.webex.com/uconnhealth/j.php?MTID=mdacf393cf6a2ee5314a3b76525ea5e57

Speaker: Dr. Coralie Dessauges, Ph.D., Research Fellow in Therapeutic Science, Harvard Medical School

Title: “Prolonged BRAF targeted therapy generates spatially organized lineage states with distinct signaling dependencies”

Abstract: While targeted inhibition of the MAPK/ERK pathway has transformed the treatment of BRAFV600E melanoma, resistance inevitably develops within months. Whereas late resistance is often driven by secondary mutations, increasing evidence supports a role for early non-genetic mechanisms that enable cancer cells to survive before such mutations arise. These include rapid adaptations in signaling and cell-cycle state, as well as longer-term changes in cell identity through lineage plasticity. However, how these processes interact over the course of treatment remains poorly understood. Here, we use a longitudinal approach combining live- and fixed-cell imaging to monitor melanoma cell adaptation at single-cell resolution from days to weeks of BRAF targeted therapy. We find that prolonged treatment leads to the establishment of a dynamic equilibrium in which most cells are arrested, yet proliferating and dying cells persist at all time points. Within this equilibrium, cells transition into two coexisting NGFR-high and NGFR-low lineage states that self-organize into spatially distinct subcommunities. Functional studies reveal that these subpopulations rely on different signaling programs to survive under BRAF inhibition: NGFR-low cells rely on transient collective ERK signaling reactivation, whereas NGFR-high cells depend on AKT signaling activation. These differences translate into complementary therapeutic vulnerabilities, with ERK and AKT pathway inhibition preferentially targeting distinct fractions of the surviving population.

Altogether, our work shows that adaptation to BRAF targeted therapy involves multiple lineage-specific mechanisms and underscores the need for longitudinal single-cell approaches to capture the dynamic and heterogeneous nature of this process.

Guest Host: Dr. Sarvenaz Sarabipour

Speaker: Edwin Appiah

Title: 

Via Webex: https://uconnhealth.webex.com/uconnhealth/j.php?MTID=mdacf393cf6a2ee5314a3b76525ea5e57

Speaker: Shivinder Singh-Bhagania

Title: 

Via Webex: https://uconnhealth.webex.com/uconnhealth/j.php?MTID=mdacf393cf6a2ee5314a3b76525ea5e57