Christina Sigurdson
University of California-San Diego, CA·Neuroscience
Prion diseases are rare brain disorders that are always fatal. Patients lose memory and movement quickly, often dying within six months of the first symptoms.
- Fields
Neuroscience
Biochemistry
Medicine & Clinical Research
- Topics
prion disease
prions
prion protein
- Grants
- 4 known grants, through May 2027
What they work on
- 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.
- Map the PrPC signaling network at the neuron membrane, and how it changes after PrPC is triggered, using highly sensitive quantitative proteomics in human iPSC-derived neurons.
- Test how the ESCRT disposal protein Hrs affects synapse activity, structure, proteins and signaling in uninfected and prion-infected neurons, using electrophysiology and correlative light-electron microscopy.
- Determine how distinct prion forms disrupt the ESCRT pathway at glutamate-using synapses, and whether glutamate receptor activity drives prion spread and neurodegeneration, comparing results with human prion-affected brain.
- Measure how a disease-causing point mutation in PrPC alters synaptic proteins, glutamate receptor function and the cell's endolysosomal recycling system, using a knock-in mouse model and its cultured neurons.
- Define the protein partners and phosphorylation network of mutant PrP in the mouse brain by tandem mass tag mass spectrometry, and compare them with prion-infected mouse and human brain.
- Genetically alter heparan sulfate chains in neurons, astrocytes and blood vessel cells of mice to test how this sugar co-factor affects which cells prions target and how long animals survive.
- Determine how heparan sulfate slows clearance of PrP through the brain's interstitial fluid, using conditional HS mouse models and radiolabeled PrP.
- Test whether antisense oligonucleotides that block heparan sulfate-making enzymes or Prnp mRNA reduce prion plaques when given at early and middle stages of disease in a mouse model.
More about the research
They are caused by the prion protein (PrP) misfolding into clumps that spread through the brain. Like Alzheimer's disease, prion diseases involve protein aggregates and massive loss of synapses, the connections between nerve cells. The work asks how the normal form of the protein on neurons, called PrPC, sets off harmful signals that damage synapses, and how host molecules help prions clump and spread. Four projects approach this from different angles: early signaling in human neurons, a synapse-clearing pathway, a mutant mouse model, and the sugar-like molecules that help prions form plaques.
Why it matters
Prion diseases have no curative treatment. By defining the signals that drive synapse loss and neuron death, and the HS interactions that let prions form plaques and resist clearance, this work could reveal new drug targets. It will directly test whether ASOs that reduce PrP or HS can slow plaque buildup in a disease model. Because prion and Alzheimer's disease share features such as synapse loss, the insights may also inform research on Alzheimer's disease.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Linda C Hsieh-Wilson
California Institute of Technology, CA·Chemistry
Map glycosaminoglycans (GAGs) in the hypothalamus and disrupt them in animal models to test effects on food intake, body weight and blood sugar control.
Charleen T Chu
University of Pittsburgh, PA·Neuroscience
Test whether loss of PINK1, a mitochondrial enzyme, impairs the transport of mitochondria into dendrites, using molecular genetic manipulations in Pink1-knockout mouse neurons and patient iPSC-derived cortical neurons.
Jennifer Freeman
Purdue University, IN·Neuroscience
Compare the immediate effects of developmental exposure to legacy PFOA and replacement PFAS (PFBA, GenX) on dopamine neurons, using zebrafish and human iPSC-derived dopamine neurons.
The school
University of California-San Diego: 84 labs on PI Pages, $1.9B a year on research, 637 research doctorates a year.
Reach out
A start for your email. Fill in the brackets.