The Herbert and Florence Irving Institute for Cancer Dynamics will continue its seminar series on the topic of mathematical sciences underpinning cancer research. The monthly seminars take place on the second Wednesday of the month, 2:00-3:00 PM EST. The presentations are open to the Columbia community (in person and online) and to researchers outside Columbia (via Zoom).
On Wednesday, December 4th (2:00 PM ET), IICD welcomes Livnat Jerby, Assistant Professor, Department of Genetics, Stanford University. Seminar hosted by Sanja Vickovic. The seminar will take place in person in Schermerhorn Hall 603 (Morningside Heights campus). If you wish to attend the seminar remotely, please register using the following link: https://columbiauniversity.zoom.us/meeting/register/tJUqfu6tpjkqGdH9-POf628HWa-Q_vsFwPx9
Title: Towards New Mechanisms to Unleash Targeted Immune Responses
Abstract: Immune responses have a remarkable ability to eliminate unhealthy cells while sparing healthy ones. In this talk I will describe our ongoing efforts to decipher, redirect, and ultimately generate new types of immune responses for disease treatment and prevention by: (1) mapping the logic of immune cell migration and redirecting immune cells to specific sites in the body and within a target tissue; (2) developing RNA-based interventions to target cell autonomous immune evasion mechanisms that stand in the way of immune surveillance, and (3) decoupling multicellular processes in the tissue context. More specifically, performing CRISPR activation screens in cytotoxic lymphocytes (CTLs) we have leveraged directed evolution and identified cell engineering strategies to redirect CTLs to migrate to and infiltrate different types of solid tumors. We found that engineering CTLs to express a unique family of (non-chemokine) receptors redirects CTLs to the tumor through sensing of a specific set of underappreciated chemoattractants, revealing a novel and programmable recruitment mechanism that we show can form a basis for new cell therapies. Alongside CTL recruitment, our work demonstrated that CTLs will not be effective without the cooperation of their target cells and identified a novel RNA-based synthetic lethality mechanism that can help ensure this cooperation and proper initiation of programmed cell death in the target cells. This RNA-based intervention enhances immune surveillance and selective elimination of cancer, virally infected, and potentially other dysfunctional (e.g., senescent) cells. Lastly, I will describe new datasets and tools that we have generated and developed to identify the drivers of multicellular processes, including recent work where we mapped genetic cell state regulators and tumor spatial organization across 2.5 million cells and 130 tumors to identify immune evasion drivers in patients (Yeh et al., Nature Immunology 2024).
Bio: Livnat Jerby is an Assistant Professor in the Department of Genetics at Stanford University, a Chan Zuckerberg Biohub Investigator, and a Paul Allen Distinguished Investigator. In the last four years, her laboratory at Stanford Genetics has identified and developed mechanisms to enhance targeted immune responses via RNA-base and cell-engineering-based interventions. Her work has been generously supported by the Cancer Research Institute, the Burroughs Wellcome Fund, Ovarian Cancer Research Alliance, Schmidt Family Foundation, Rothschild Foundation, Paul G. Allen Family Foundation, Bill and Melinda Gates Foundation, Basser Center for BRCA, Chan Zuckerberg Biohub initiative, Stanford Cancer Institute, and the National Institute of Health.
