James LaBelle
University of Chicago, IL·Microbiology & Immunology
Drugs that make cancer cells self-destruct are increasingly used in medicine, but how do they affect the immune cells that patients also rely on? BCL-2 family proteins sit at the mitochondria and control apoptosis, a cell's programmed death, through a balance of pro-death and anti-death partners.
- Fields
Microbiology & Immunology
Pharmacology
Biochemistry
- Topics
BCL-2 family
BH3 mimetics
venetoclax
- Grants
- 1 known grant, through Apr 2031
What they work on
- Test whether venetoclax and other BH3 mimetics, drugs that block anti-death BCL-2 proteins, alter the function of CAR T cells made from healthy donors and heavily pretreated patients.
- Map protein-protein interactions within the BCL-2 family network in CAR T cells at baseline and after BH3 mimetic treatment to identify how the drugs modulate immune function.
- Determine how changes in BCL-2 family interactions control T cell effector function, plasticity and mitochondrial dynamics through apoptotic, genetic and metabolic adaptations.
More about the research
BH3 mimetics such as venetoclax pull these partners apart to kill cancer cells. Immune cells, especially T cells, depend heavily on BCL-2 proteins throughout their lives, and new evidence suggests blocking some of these proteins changes immune function in ways unrelated to cell death.
Why it matters
Defining how BH3 mimetics reshape T cells could expand use of this drug class as immune-modulating agents, potentially improving CAR T cell therapies for patients, and could uncover new drug targets that control immune function across a wide range of diseases.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
David Akhavan
University of Kansas, KS·Biomedical Engineering
Develop nanocarriers, tiny drug-carrying particles, that can be loaded into CAR T cells, which are engineered tumor-targeting immune cells, to create a platform for delivering drugs into glioblastoma.
Mohamad Hamieh
Weill Medical College of Cornell University, NY·Microbiology & Immunology
Test strategies to reduce ICANS, the neurotoxicity of CAR T-cell therapy, by targeting extracellular vesicles released by activated CAR T cells, using animal models that track blood-brain barrier integrity and antitumor activity.
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.
The school
University of Chicago: 39 labs on PI Pages, $681M a year on research, 457 research doctorates a year.
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