Nicole Steinmetz
University of California-San Diego, CA·Biomedical Engineering
Viruses that infect plants cannot infect people, but the immune system still treats them as danger signals. That reaction can be put to work as medicine.
- Fields
Biomedical Engineering
Microbiology & Immunology
Medicine & Clinical Research
- Topics
cowpea mosaic virus
plant virus nanoparticles
virus-like particles
- Grants
- 4 known grants, through Jul 2029
What they work on
- Determine how cowpea mosaic virus (CPMV) trains innate immune cells, by stimulating cells in culture and challenging them with bacterial LPS while using ChIP and ATAC sequencing to detect epigenetic rewiring and metabolic change.
- Test whether CPMV-induced protection depends on innate or adaptive immunity, using B16F10 melanoma in wild-type, Rag1-knockout and CCR2-knockout mice with β-glucan as benchmark, and single-cell profiling of blood-forming stem and progenitor cells.
- Test whether prior CPMV exposure protects mice from influenza virus challenge and pathology, benchmarked against the FluMist vaccine and the fungal sugar β-glucan.
- Build CPMV virus-like particles displaying S100A9, an inflammation-driving myeloid protein, and ask whether the resulting antibodies lower S100A9 levels, inflammatory signals and cholesterol in mouse atherosclerosis models.
- Develop a dual-target vaccine combining S100A9 with PCSK9, a cholesterol checkpoint, and test whether attacking inflammation and cholesterol together improves protection, including in aging, chemotherapy and tumor-bearing mice.
- Formulate slow-release CPMV-polymer implants and microparticles by hot melt extrusion, tune release rate, and confirm that released particles retain structure and immune activity.
- Compare efficacy, mechanism and safety of CPMV implants across doses in immune-competent mouse models of metastatic triple-negative, HER2+ and ER+ breast cancer, then in a phase 0 trial of companion dogs with mammary tumors.
- Test whether intratumoral CPMV synergizes with immune checkpoint blocking antibodies by increasing tumor-antigen-specific effector T cells in triple-negative breast cancer models.
- Define the pharmacology and mechanism of S100A9-targeted CPMV given into the bloodstream, asking whether it concentrates at metastatic sites and prevents metastatic outgrowth.
More about the research
Research here builds nanoparticles from cowpea mosaic virus (CPMV), a plant virus whose protein shell can be produced in plants, and uses it to wake up the body's fast-acting "innate" immune cells. Four projects extend this one platform in different directions: understanding why CPMV is such a strong immune stimulant and whether it can train the immune system against future threats, turning it into a vaccine against cardiovascular disease, engineering slow-release implants so tumors need fewer injections, and combining it with checkpoint drugs and tumor-homing targeting for triple-negative breast cancer. Across projects the work moves from mechanism in cells and mice toward testing in pet dogs with naturally occurring tumors.
Why it matters
Cancer immunotherapies that are injected into tumors, and lifelong drugs for heart disease, both run into cost, side effects and patient compliance. A plant virus particle grown in plants offers a potentially inexpensive way to stimulate immunity: as a tumor injection or slow-release implant for breast cancer, as a vaccine aimed at arterial inflammation and cholesterol, and as a possible way to prime broad protection against infections such as influenza. Companion dogs with spontaneous tumors would be treated while informing human translation.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Mostafa Yazdi
Missouri University of Science and Technology, MO·Biomedical Engineering·Early-career
Evaluate the anti-tumor activity of the Tumor-derived Cell-membrane Coated NanoVaccine (TCC-NV), adjuvant-loaded particles wrapped in tumor cell membranes, in immune-competent mouse models of triple-negative breast cancer.
Ashish Ranjan
University of Texas Southwestern Medical Center, TX·Biomedical Engineering
Determine how well histotripsy plus anti-CD40 antibody microparticles works in mouse melanoma models that differ in immune visibility and tumor burden.
Eric Ubil
University of Kentucky, KY·Microbiology & Immunology
Determine how tumor cells regulate secretion of proteins that activate the macrophage Mer receptor, and test whether their levels in human tumors predict response to chemotherapy.
The school
University of California-San Diego: 84 labs on PI Pages, $1.9B a year on research, 637 research doctorates a year.
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