Charleen T Chu
University of Pittsburgh, PA·Neuroscience
Memory depends on dendritic spines. These are tiny bumps on the branches of brain cells where connections with other neurons form.
- Fields
Neuroscience
Medicine & Clinical Research
Biology
- Topics
Parkinson's disease
Lewy body dementia
Alzheimer's disease
- Grants
- 1 known grant, through Jun 2029
What they work on
- 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.
- Determine how PINK1 regulates mitochondrial motor proteins and the positioning of mitochondria next to synapses, including a PINK1-regulated phosphorylation site on a motor protein.
- Measure whether PINK1 deficiency weakens mitochondrial support of synaptic plasticity, using glutamate uncaging to stimulate single spines and electrophysiology to record neuron responses.
- Assess how PINK1 loss affects dendritic spine dynamics and cognitive function in living Pink1-knockout mice.
More about the research
Losing these connections is a major structural sign of dementia, seen in Alzheimer's disease and in Lewy body dementia (LBD). Mutations in PINK1 (PTEN-induced kinase 1), an enzyme that works at mitochondria, the cell's energy producers, cause early-onset Parkinson's disease (PD), often with dementia. Normal PINK1 is also reduced in the brain's cortex in patients with ordinary, non-inherited PD dementia and Alzheimer's disease. This raises the question of how PINK1 keeps neurons and their connections healthy.
Why it matters
Parkinson's disease and related dementias steadily destroy the brain connections that support thinking and memory. By showing how PINK1 keeps dendrites and synapses supplied and functioning, this work could point to new strategies for protecting brain cells. Such strategies could slow cognitive decline in patients with Parkinson's disease, Parkinson's disease dementia, Lewy body dementia and possibly Alzheimer's disease.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Jason Weick
University of New Mexico, NM·Neuroscience
Correlate NSG1 and NSG2 levels with AD and FTD subtypes and Sortilin-1 cleavage in post-mortem human and rodent brain samples.
Nicholas Seyfried
Emory University, GA·Biochemistry
Build a longitudinal Lewy body dementia registry under the Parkinson's Disease Biomarker Program, collecting clinical data and biospecimens to support validation of protein biomarkers.
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.
The school
University of Pittsburgh: 83 labs on PI Pages, $1.5B a year on research, 403 research doctorates a year.
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