Steven L. Gonias
University of California-San Diego, CA·Microbiology & Immunology
Inflammation protects the body but also drives damage in many diseases, from colitis and arthritis to Alzheimer's and Parkinson's disease. Both projects study natural "off switches" for inflammation.
- Fields
Microbiology & Immunology
Biochemistry
Neuroscience
- Topics
inflammation
innate immunity
microglia
- Grants
- 2 known grants, through Jun 2029
What they work on
- Test whether anti-inflammatory derivatives of cellular prion protein (PrPC) reduce microglia and astrocyte activation triggered by amyloid-β, Tau and α-synuclein, proteins that aggregate in neurodegenerative diseases.
- Determine how deleting or overexpressing the PrPC gene (Prnp) changes neuroinflammation biomarkers in AppNL-F, P301S-Tau and α-synuclein fibril-injected mouse models, including tga20 mice with extra PrPC.
- Test whether PrPC-derived proteins and short peptides given systemically use LRP1 to cross the blood-brain barrier and boost the anti-inflammatory LRP1/NMDA receptor system in microglia.
- Identify the structural parts of tissue-type plasminogen activator (tPA) needed to block inflammation, and engineer improved enzymatically inactive tPA (EI-tPA) variants as candidate drugs.
- Define tPA signaling downstream of the NMDA receptor, including Trk receptor activation by Src kinases, and test in mice lacking NMDA-R in immune cells whether EI-tPA needs it to neutralize LPS toxicity.
- Use single-cell transcriptome profiling in the DSS colitis mouse model to identify colon cells targeted by EI-tPA and the pathways behind its benefit.
More about the research
Proteins best known for other jobs can bind a pair of receptors on immune cells and calm them down. The receptors are LRP1 (LDL receptor-related protein-1) and the NMDA receptor (NMDA-R). One protein is the cellular prion protein (PrPC), and the other is the clot-dissolving enzyme tPA. The lab aims to understand these pathways and to test whether they can be turned into anti-inflammatory therapies.
Why it matters
These pathways could lead to new anti-inflammatory drugs. Engineered tPA variants could help inflammatory conditions such as colitis and arthritis. Prion-protein-based peptides delivered into the brain could reduce neuroinflammation in Alzheimer's disease, Parkinson's disease and tauopathies. The work also clarifies how blood-clotting systems and immunity interact.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Steven Boeynaems
Baylor College of Medicine, TX·Neuroscience·Early-career
Define the biophysical rules by which neuropathological proteins form condensates with nucleic acids that mimic antimicrobial peptides and boost Toll-like receptor immune signaling, using in vitro biophysical approaches.
Christina Sigurdson
University of California-San Diego, CA·Neuroscience
Determine how an anti-PrP antibody or purified infectious prion oligomers trigger synaptic kinase signaling (enzymes that add phosphate tags) in neurons derived from human induced pluripotent stem cells.
Yohei Kirino
Thomas Jefferson University, PA·Biochemistry
Determine how RNase Kappa, a newly found enzyme that makes cyclic phosphate-containing RNAs, and two cP-RNA-stabilizing proteins control cP-RNA levels, using cP-RNA-seq.
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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