Barbara Engelhardt

Thursday, February 6, 2025

4:00 - 5:00 pm (refreshments at 3:30 pm)

Monadnock (Merkin building/415M 2040)

Add to your calendar

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.

‍

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.

‍

Biography:

Barbara Engelhardt is a Senior Investigator at Gladstone Institutes and Professor at Stanford University in the Department of Biomedical Data Science. She received her B.S. (Symbolic Systems) and M.S. (Computer Science) from Stanford University and her PhD from UC Berkeley (EECS) advised my Prof. Michael I Jordan. She was a postdoctoral fellow with Prof. Matthew Stephens at the University of Chicago. She was an Assistant Professor at Duke University from 2011-2014, and an Assistant, Associate, and then Full Professor at Princeton University in Computer Science from 2014-2022. She has worked at Jet Propulsion Labs, Google Research, 23andMe, and Genomics plc. In her career, she received an NSF GRFP, the Google Anita Borg Scholarship, the SMBE Walter M. Fitch Prize (2004), a Sloan Faculty Fellowship, an NSF CAREER, and the ISCB Overton Prize (2021). Her research is focused on developing and applying models for structured biomedical data that capture patterns in the data, predict results of interventions to the system, assist with decision-making support, and prioritize experiments for design and engineering of biological systems.

‍

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. 

Questions? Email Amanda Ogden at aogden@broadinstitute.org.