Tracy Hagemann
University of Wisconsin-Madison, WI·Neuroscience
Why do some children with a rare brain disease stop growing and keep vomiting, even when they are fed? Alexander disease is a severe neurodegenerative disorder caused by mutations in GFAP (glial fibrillary acidic protein), a structural protein made by astrocytes, the star-shaped support cells of the brain.
- Fields
Neuroscience
Medicine & Clinical Research
Genetics
- Topics
Alexander disease
AxD
astrocytes
- Grants
- 1 known grant, through Jun 2027
What they work on
- Test whether GDF15 levels track failure-to-thrive symptoms in Gfap+/R237H rats by lowering GFAP with antisense oligonucleotides and measuring GDF15, GFRAL neuron activation and weight gain.
- Measure GDF15 in spinal fluid and plasma from Alexander disease patients in a natural history study and compare it with vomiting, growth and MRI lesion locations.
- Determine whether the integrated stress response, a cellular alarm program, drives GDF15 in astrocytes by altering it with drugs in rats and mapping cells with single-nucleus and spatial transcriptomics.
- Test whether GDF15 is the main cause of failure to thrive by blocking its receptor GFRAL with antibodies or knocking down GDF15 in the rat brainstem.
More about the research
The mutant protein clumps inside astrocytes and damages them. Many patients show failure to thrive, meaning poor weight gain and growth, along with frequent vomiting. Current treatments, such as nutritional supplements and feeding tubes, are invasive and often do not work.
Why it matters
Children and adults with Alexander disease often suffer from vomiting and poor growth that feeding tubes and supplements do not fix. If GDF15 drives these symptoms, blocking it or its receptor could offer a new way to prevent them, and GDF15 could serve as a biomarker. Insight into how stressed astrocytes affect the body may also inform other disorders with abnormal astrocytes, such as Alzheimer's and Parkinson's disease.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
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Harvard University, MA·Neuroscience
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Charles Brown
Stanford University, CA·Medicine & Clinical Research
Test whether cerebrospinal fluid markers of blood-brain barrier leak, inflammation, and neuron and astrocyte injury — including the CSF/blood albumin ratio, cytokines, neurofilament light and glial fibrillary acidic protein — are associated with delirium after aortic surgery in 180 patients with CSF drains.
Seunghye Han
Northwestern University, IL·Medicine & Clinical Research
Test whether a raised mitochondrial NADH/NAD+ ratio and the protein DELE1 are needed to activate the integrated stress response that blocks AT2-to-AT1 lung cell maturation when mitochondrial complex I is lost.
The school
University of Wisconsin-Madison: 91 labs on PI Pages, $1.9B a year on research, 854 research doctorates a year.
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