Geoffrey Markowitz
Rutgers University-New Brunswick, NJ·Microbiology & Immunology
Immunotherapies work by unleashing the body's own killer immune cells against tumors, but not all of those cells are equally useful. Among CD8+ T cells, which directly kill tumor cells, a subset marked by the protein TCF1 behaves like a reservoir of progenitors: it keeps producing fresh fighters and gives a longer-lasting response than the more short-lived effector-like cells that lack TCF1.
- Fields
Microbiology & Immunology
Biochemistry
Medicine & Clinical Research
- Topics
CD8+ T cells
progenitor-exhausted T cells
T cell exhaustion
- Grants
- 1 known grant, through Aug 2027
What they work on
- Identify metabolic enzymes whose loss increases generation of TCF1+ progenitor-exhausted CD8+ T cells, using a CRISPR/Cas9 knockout screen in vitro across T cells with different T-cell receptor affinities.
- Map how TCF1+ and TCF1- CD8+ T cells differ in fuel use during activation, using U-13C glucose stable isotope tracing under weak and strong T-cell receptor stimulation.
- Test whether manipulating validated metabolic targets improves anti-tumor activity, using mouse tumor models and an immunocompetent organoid system derived from human patient tumors.
- Define the shared and divergent features of TCF1+ progenitor-like T cells induced by different drugs and cytokine cocktails, by comparing their transcriptomes and metabolomes.
More about the research
How this progenitor state is created and kept is not understood, which limits how well it can be exploited. The question here is whether the state can be dialed up by changing how T cells handle fuel, since the metabolic pathways a T cell uses are closely tied to the kind of cell it becomes.
Why it matters
T-cell therapies and checkpoint immunotherapies help many cancer patients, but responses often fade. If metabolic drugs or culture conditions can reliably generate and sustain the long-lived TCF1+ CD8+ T cell population, it may be possible to make these treatments more durable, and the transcriptomic and metabolic profiles produced here could serve as benchmarks for assessing T-cell quality.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Willy Hugo
University of California-Los Angeles, CA·Microbiology & Immunology
Test whether long-term glioblastoma survivors after ATL-DC vaccination have more stem-like, progenitor-exhausted TCF7+ PD1+ CD8 T cells in their tumors, using spatial transcriptomics and high-plex immunofluorescence.
Nu Zhang
University of Texas Health Science Center at San Antonio, TX·Microbiology & Immunology
Determine how TRM-stem cells, Tcf-1+ stem-like CD8+ T cells that become resident in tumor-draining lymph nodes, are related to other T cell subsets there, by tracking tumor-specific T cells in mouse tumor models.
Hussein Sultan
Washington University in St Louis, MO·Microbiology & Immunology
Determine how the EBI3 subunit of the suppressive cytokine IL-35 drives induction of Tr1 regulatory CD4 T cells, using IL-35 reporter mice in established tumor models to identify which cells produce it.
The school
Rutgers University-New Brunswick: 57 labs on PI Pages, $837M a year on research, 713 research doctorates a year.
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