Hiroko Yano
Washington University in St Louis, MO·Neuroscience
Huntington's disease is an inherited, fatal brain disorder caused by an abnormally long stretch of repeated glutamine amino acids in a protein called huntingtin. Neurons die progressively, especially in the striatum, a deep brain region controlling movement, and in the cortex.
- Fields
Neuroscience
Genetics
Pharmacology
- Topics
Huntington's disease
huntingtin
polyglutamine repeat
- Grants
- 1 known grant, through Feb 2027
What they work on
- Determine how a DNA methyltransferase inhibitor alters gene expression in individual brain cell types, including striatal neurons and glia, in Huntington's disease model mice, using single-nucleus RNA sequencing.
- Test whether treatment with the hypomethylating agent improves motor and behavioral deficits in two different mouse models of Huntington's disease.
- Assess whether the demethylating treatment reduces neuropathology, including the loss of vulnerable striatal and cortical neurons, in Huntington's disease mice.
- Identify which DNA methylation-mediated transcriptional changes are critical for neuronal function and survival, and whether blocking them accounts for any neuroprotection observed.
More about the research
Why these particular cells die is still unclear, and no treatment slows the disease. One of the earliest molecular abnormalities seen is widespread disruption of gene expression — which genes are switched on and off. Growing evidence points to DNA methylation, a chemical tag that cells place on DNA to silence genes, as a driver of that disruption. This project tests whether removing those tags protects the brain.
Why it matters
There is no therapy that slows Huntington's disease. By testing a DNA demethylating drug in mouse models and measuring the response of each brain cell type, the project could supply preclinical evidence for a new class of disease-modifying treatment and clarify how such treatment protects neurons. The same epigenetic strategy may be relevant to other neurological disorders in which abnormal DNA methylation has been implicated.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Srinivasa Subramaniam
Florida Atlantic University, FL·Neuroscience
Identify the protein and RNA components on ribosomes that interact with mutant huntingtin (mHTT), the toxic protein that causes Huntington disease, using biochemical approaches.
Han Tan
University of California-Irvine, CA·Neuroscience·Early-career
Test whether BNC2 neurons, leptin-sensing cells in the hypothalamic arcuate nucleus, control the function of glucose-regulating organs through direct nerve connections.
Marianne Seney
University of Pittsburgh, PA·Neuroscience
Determine whether somatostatin-expressing neurons in human prefrontal cortex show pronounced transcriptional changes in people with opioid use disorder who also used nicotine, using postmortem brain tissue.
The school
Washington University in St Louis: 97 labs on PI Pages, $1.2B a year on research, 365 research doctorates a year.
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