Patrick S. Stayton
University of Washington, WA·Biomedical Engineering
Lung infections can turn deadly fast, and drugs given by mouth or vein often fail to reach the lung cells where viruses and bacteria hide, at high enough levels and for long enough. Both projects in this lab build on one shared tool: "drugamers," polymeric prodrugs.
- Fields
Biomedical Engineering
Pharmacology
Microbiology & Immunology
- Topics
polymeric prodrug
drugamer
inhalation therapy
- Grants
- 2 known grants, through Jun 2029
What they work on
- Develop remdesivir and baricitinib as polymeric prodrug ("drugamer") candidates, using mannose tags to target alveolar macrophages and peptide ligands to target lung epithelial viral reservoirs for extended inhaled dosing.
- Characterize how drugamers load drug into lung macrophage and epithelial cells and how long dosing persists, using quantitative LC-MS pharmacokinetics and lung inflammatory response assays for safety.
- Test and optimize drugamers and drugamer combinations against SARS-CoV-2 in hACE2 mice, which express the human viral entry receptor, measuring viral load and survival.
- Build a panel of host-directed immune modulators as macrophage-targeted polymeric prodrugs to concentrate drug inside the intracellular lung compartment with extended release.
- Identify which immune-modulatory pathways improve treatment and prophylaxis in aerosolized F. novicida and B. thailandensis mouse models, and test them combined with a ciprofloxacin polymeric prodrug.
- Assess up-selected immune-modulator plus antibiotic prodrug combinations against aerosolized Francisella tularensis and Burkholderia pseudomallei in high-containment rodent disease models, seeking combinations active against both pathogens.
More about the research
These are chain-like polymer molecules that carry drug molecules attached along their length and release them gradually. They are made to be inhaled from nebulizers and distributable inhalation devices, and they direct drugs into specific lung cell reservoirs, especially the alveolar macrophage, an immune cell that patrols the lung's air sacs. Compared with conventional formulations, the platform carries more drug per particle, can combine very different drugs in one dose for combination therapy, and lets each drug's release profile be tuned to avoid a sudden burst. One project applies this to coronaviruses, the other to bacterial biodefense threats.
Why it matters
Inhaled, slow-release drug carriers could give patients with COVID-19 or future coronavirus outbreaks a treatment usable before hospitalization and in settings without infusion facilities, and could protect caregivers. For tularemia and melioidosis, both biodefense and global health threats with rising antibiotic resistance, a single inhaled dose combining immune-modulating and antibacterial drugs may offer multi-day protection where daily pill-taking is unreliable.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Shelton Wright
University of Washington, WA·Microbiology & Immunology·Early-career
Determine the role of gamma-delta T cells, mucosa-enriched T cells that respond rapidly like innate immune cells, in driving lung inflammation during pulmonary melioidosis in vivo.
Daniel Voth
University of Arkansas for Medical Sciences, AR·Microbiology & Immunology
Identify which neurotransmitter signaling machinery in human alveolar macrophages Coxiella burnetii needs to replicate, using host-directed drugs that block these pathways.
Ying Fang
University of Illinois Urbana-Champaign, IL·Microbiology & Immunology
Generate and characterize SARS-CoV-2-specific antibody reagents and diagnostic standards for COVID-19 research and diagnostics.
The school
University of Washington: 81 labs on PI Pages, $1.7B a year on research, 694 research doctorates a year.
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