Guangyong Peng
Washington University in St Louis, MO·Microbiology & Immunology
T cells can kill tumor cells, but inside tumors they often stop working. One cause is regulatory T cells (Treg cells), immune cells that normally calm immune responses.
- Fields
Microbiology & Immunology
Medicine & Clinical Research
Neuroscience
- Topics
T cell senescence
regulatory T cells
Treg
- Grants
- 4 known grants, through Jul 2028
What they work on
- Identify how human Treg cells rewrite lipid metabolism and fate in responder T cells, focusing on the energy sensor AMPK, ATM DNA-damage signaling, and MAPK signaling.
- Test whether activating TLR8, an immune sensor, in Treg cells while blocking ATM or MAPK signaling in tumor-specific T cells reverses senescence and strengthens anti-tumor responses.
- Determine whether excess lipid metabolism, including lipid droplet buildup and secreted lipids, is required for Treg cells to make effector T cells senescent and suppressive.
- Test whether lipid metabolic reprogramming plus anti-PD-L1 checkpoint blockade revives senescent and exhausted tumor-specific T cells, using mouse adoptive T cell transfer tumor models.
- Identify which lipid species change in dendritic cells made senescent by breast tumor γδ Treg cells, and test the roles of STAT transcription factors and PD1-PDL1 signaling in those changes.
- Identify the key glucose metabolites TLR8 signaling controls in human γδ Treg cells, then test TLR8 activation combined with PD-L1 blockade in dendritic cells as a breast cancer strategy.
- Determine whether lipids and metabolites secreted by senescent T cells reprogram human neuronal cells toward amyloid beta and Tau aggregation, hallmarks of Alzheimer's disease.
- Test in SAMP8 mice, a strain that ages prematurely, whether accumulated senescent T cells drive Alzheimer's progression, and whether lipid reprogramming that reverses senescence prevents it.
More about the research
A central question here is how Treg cells push other immune cells into senescence, a worn-out state, and whether that state can be reversed. Senescent T cells and dendritic cells (cells that alert T cells to threats) do not merely stop working; they become suppressive themselves and spread the shutdown. Four projects ask how shifts in cell metabolism, especially the handling of fats (lipids) and sugar, drive this process, with applications to cancer immunotherapy, breast cancer, and Alzheimer's disease.
Why it matters
Checkpoint immunotherapy helps only roughly 15–35% of patients. Reversing T cell senescence could extend the benefit of checkpoint and T cell transfer therapies to more people, including women with breast cancer, the second leading cause of cancer death in women worldwide. The same metabolic targets may also suggest ways to prevent or treat Alzheimer's disease, the most common cause of dementia.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Excessive lipid metabolism in T cell senescence and immunosuppression
NIH · Aug 2023 – Jul 2028
Metabolic Control of T Cell Senescence in Pathogenesis and Immunotherapy of Alzheimer's Disease
NIH · Sep 2022 – Apr 2027
Targeting T Cell Senescence and Dysfunction for Anti-tumor Immunity
NIH · Mar 2020 – Feb 2027
Closest labs
Drew Pardoll
Johns Hopkins University, MD·Microbiology & Immunology
Identify molecules made by regulatory T cells (Tregs), immune cells that suppress other immune cells, that are found specifically in tumors of patients who do not respond to anti-PD-1 or anti-PD-L1 therapy.
Jin Xie
University of Georgia, GA·Biomedical Engineering
Test whether anti-CD205 antibody-conjugated calcium nanoparticles (αCaNPs) selectively raise cytosolic calcium in circulating cDC1 dendritic cells and increase their infiltration into tumors in murine head and neck cancer models.
Masanobu Komatsu
Johns Hopkins University, MD·Microbiology & Immunology
Test whether the signaling protein R-Ras in blood vessel cells drives the formation of high endothelial venules in tumors, using mice that lack or overproduce endothelial R-Ras in mammary tumor and melanoma models.
The school
Washington University in St Louis: 97 labs on PI Pages, $1.2B a year on research, 365 research doctorates a year.
Reach out
A start for your email. Fill in the brackets.