Schmidt Center - MIT EECS Colloquium, featuring Barbara Engelhardt (Gladstone Institutes, Stanford University)
Thursday, February 6, 2025 4pm to 5pm
About this Event
415 Main Street, Cambridge, MA 02142
https://www.ericandwendyschmidtcenter.org/events/barbara-engelhardtThursday, February 6, 2025
4:00 - 5:00 pm
Monadnock (Merkin building/415M 2040)
Please join us for a colloquium featuring Barbara Engelhardt, Senior Investigator at Gladstone Institutes and Professor in the Department of Biomedical Data Science at Stanford University, on Machine learning to analyze cellular behavior in live-cell imaging experiments of T cell—cancer cell co-cultures.
This colloquium is part of a series hosted jointly by the Eric and Wendy Schmidt Center at the Broad Institute and the Department of Electrical Engineering and Computer Science at MIT. Barbara’s colloquium will run from 4:00-5:00 pm with refreshments served at 3:30 pm.
The colloquium will be held at the Broad Institute in Monadnock as well as virtually via YouTube Livestream: broad.io/ewsc. If you do not have a Broad badge, please show up at the 415 Main Street entrance 10 minutes prior to the event to be escorted to the talk.
Questions? Email Amanda Ogden at aogden@broadinstitute.org.
Abstract:
T cell therapies, such as chimeric antigen receptor (CAR) T cells and T cell receptor (TCR) T cells, are a growing class of anti-cancer treatments. However, expansion to novel indications and beyond last-line treatment requires engineering cells’ dynamic population behaviors. Here we develop the tools for cellular behavior analysis of T cells from live-cell imaging, a common and inexpensive experimental setup used to evaluate engineered T cells. In this talk, I will first describe segmentation and tracking using Van Valen Lab's Caliban software. Then, I will discuss our Occident pipeline, developed to collect a catalog of phenotypes that characterize cell populations, morphology, movement, and interactions in co-cultures of modified T cells and antigen-presenting tumor cells. We use Caliban and Occident to interrogate how interactions between T cells and cancer cells differ when beneficial knock-outs of RASA2 and CUL5 are introduced into TCR T cells. We apply spatiotemporal models to quantify T cell recruitment and proliferation after interactions with cancer cells. We discover that, compared to a safe harbor knockout control, RASA2 knockout T cells have longer interaction times with cancer cells leading to greater T cell activation and killing efficacy, while CUL5 knockout T cells have increased proliferation rates leading to greater numbers of T cells for hunting. Together, segmentation and tracking plus phenotype quantification from Occident enable cellular behavior analysis to better engineer T cell therapies for improved cancer treatment.