Edgar G. Engleman
Stanford University, CA·Microbiology & Immunology
Most cancer deaths are caused not by the original tumor but by its spread to other organs. A puzzling feature of that spread is that it seems to require the immune system to stand down: tumors reach new sites and grow there without being attacked.
- Fields
Microbiology & Immunology
Medicine & Clinical Research
Biology
- Topics
metastasis
tumor microenvironment
macrophages
- Grants
- 2 known grants, through Jun 2031
What they work on
- Test whether macrophages carrying the erythropoietin receptor EPOR are the primary gatekeepers permitting tumors to colonize the liver, using liver-tropic orthotopic mouse models with multiplexed microscopy, flow cytometry and single-cell RNA sequencing.
- Determine whether EPO-EPOR signaling drives immune tolerance specific to the tumor, comparing transgenic mouse models of liver metastasis and validating the immunohistology findings in human tissue samples.
- Evaluate whether antibodies or decoy receptor-fusion proteins that block EPO-EPOR signaling prevent or treat liver metastasis, and whether they sensitize tumors to immune checkpoint blockade.
- Map the timeline by which tumors generate body-wide immune tolerance after lymph node colonization, using CODEX high-dimensional imaging to track local microenvironments across the host over time.
- Identify the cell-cell interactions inside tumor-involved lymph nodes that enable immune evasion, using single-cell RNA sequencing and spatial transcriptomics, then test candidate genes with CRISPR editing, cell depletion and knockout mice.
- Trace whether immune and stromal cells leaving tumor-involved lymph nodes build a pro-metastatic environment at distant organs, using a cell labeling platform to follow their movement to distant sites and back to the primary tumor.
More about the research
Both projects here investigate how tumors engineer that silence, each at a different stop along the metastatic route. One focuses on the liver, a common and dangerous destination for spreading tumors; the other on lymph nodes, the immune filtering stations that tumors typically colonize first. In both cases the question is mechanistic and the goal is a target that could be drugged to prevent or treat metastasis.
Why it matters
Metastasis causes most cancer deaths, and the liver is one of its most common and lethal destinations. If tumors depend on EPO signaling to macrophages to colonize the liver, antibodies or decoy receptors that block that signal could potentially prevent or treat liver metastasis in patients with pancreatic or colon cancer and make existing immunotherapies work in tumors that currently resist them. Mapping how lymph node metastases spread immune tolerance through the body could likewise identify targets for stopping stage III disease from progressing further.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Sana D Karam
Washington University in St Louis, MO·Microbiology & Immunology
Determine how immune checkpoint inhibitors such as anti-PD-L1 drugs act on PD-1-expressing regulatory T cells and their STAT3 signaling during radiation therapy, using genetically engineered mice and samples from HNSCC clinical trials.
Julio Aguirre-Ghiso
Albert Einstein College of Medicine, NY·Medicine & Clinical Research
Map the transcriptional and chromatin programs controlled by ZFP281, a gene-regulating protein, in early disseminated breast cancer cells and in human DCIS samples, and test how they drive both dissemination and dormancy in mouse models.
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.
The school
Stanford University: 87 labs on PI Pages, $1.6B a year on research, 739 research doctorates a year.
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