Roderick O'Connor
University of Pennsylvania, PA·Microbiology & Immunology
Engineered immune cells can cure some blood cancers, but their success hinges on stamina: a single T cell must find, attach to, and kill many tumor cells in a row. Tumors are metabolically hostile places, short on oxygen and nutrients, and a T cell that runs out of fuel stops killing.
- Fields
Microbiology & Immunology
Biochemistry
Medicine & Clinical Research
- Topics
CAR T cells
immunometabolism
serial killing
- Grants
- 1 known grant, through Feb 2028
What they work on
- Determine the separate energy costs of T cell migration versus immune synapse formation and killing, using a specialized CAR T cell conditioning regimen and real-time eSIGHT RTCA cell analysis.
- Test whether CAR T cells that can replenish spare respiratory capacity — their reserve mitochondrial power — during repetitive antigen stimulation are more efficient serial killers of tumor cells.
- Define how argininosuccinate synthase 1 (ASS1), a urea-cycle enzyme, supports mitochondrial function and tumor clearance, combining Seahorse flux assays, RNA sequencing, ATAC sequencing and in vivo tumor models.
- Test the proposed chain linking reductive glutamine metabolism, GOT1-mediated aspartate supply and ASS1-driven fumarate production to killing capacity, and compare CD28 versus 4-1BB CAR designs in hypoxic tumor models.
- Test whether extracellular fructose, which rises sharply in acute myeloid leukemia bone marrow, fuels CD123-directed CAR T cell cytotoxicity, and use single-cell RNA sequencing to identify the fructose-producing cells.
More about the research
This work asks a simple but under-studied question: what energy does each step of killing actually cost, and which metabolic pathways let chimeric antigen receptor (CAR) T cells — T cells engineered with a synthetic receptor that recognizes a tumor marker — keep going through repeated encounters with tumor cells.
Why it matters
Many patients given CAR T cell therapy for advanced blood cancers relapse because the engineered cells lose potency inside the tumor's nutrient-poor environment. Identifying the metabolic pathways and genes that sustain repeated killing could point to ways of manufacturing or conditioning CAR T products that last longer, and clarifying how tumor-derived fructose shapes immune reactivity may help explain poor responses in acute myeloid leukemia.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Corynn Kasap
University of California-San Francisco, CA·Medicine & Clinical Research·Early-career
Use computational protein engineering to build a CAR-T cell based on the natural ligand of CD70, a protein found on AML cells but largely absent from normal tissue, and test whether it clears CD70-low leukemia blasts.
Peter Chockley
Ohio State University, OH·Microbiology & Immunology·Early-career
Develop monomeric chimeric antigen receptors (single-unit CARs with a stable off state) for natural killer cells, adding immune synapse augmentation, to reduce erratic signaling and improve killing of pediatric solid tumor cells.
John Wagner
University of Minnesota, MN·Medicine & Clinical Research
Establish the safety and maximum tolerated dose of donor CAR19 regulatory T cells, given with and without IL-2, in patients with relapsed or refractory CD19+ acute lymphocytic leukemia, measuring cell persistence and tumor killing.
The school
University of Pennsylvania: 90 labs on PI Pages, $2.2B a year on research, 750 research doctorates a year.
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