PIPages
Labs

John Edwards

Washington University in St Louis, MO·Neuroscience

The brain contains a huge variety of neuron types. Each must keep a stable identity even as it adapts to changing inputs from its surroundings.

Fields

Neuroscience

Genetics

Biochemistry

Topics

epigenetics

DNA methylation

5-methylcytosine

Grants
1 known grant, through Apr 2027

What they work on

  1. Develop a nanopore long-read sequencing method that simultaneously and accurately profiles 5-methylcytosine and 5-hydroxymethylcytosine in both CG and non-CG contexts across gene promoters and gene bodies.
  2. Determine how mC and hmC patterns direct binding of MeCP2, a methyl-DNA reader mutated in Rett syndrome, to maintain distinct gene activity in cerebellar granule and Purkinje neurons.
  3. Use long-read data to dissect how allele-specific DNA methylation patterns on individual gene copies contribute to neuronal gene regulation.

More about the research

One way cells "remember" which genes to keep on or off is DNA methylation, a chemical tag added to DNA. Mutations in the proteins that write and read these tags are linked to neurodevelopmental disorders and intellectual disability. A key example is Rett syndrome, caused by mutations in MeCP2. Yet how these marks actually work in neurons is still poorly understood.

Why it matters

Mutations in DNA methylation readers and writers, such as MeCP2 in Rett syndrome and TET enzymes, are linked to neurodevelopmental disorders and intellectual disability. A single-assay long-read method for sequencing DNA and reading methylation could greatly increase the number of methylation maps available from clinical and research samples. The insights gained could suggest new therapies for these conditions.

Known grants

From NIH and NSF research grants. Labs often have other funding we can't see.

New approaches to determine the function of neuronal epigenetic marks

NIH · May 2024 – Apr 2027

Closest labs

Tomoko Yamada

Northwestern University, IL·Neuroscience

Determine how functional domains of the transcription factor Etv1 couple recruitment of target genes to ME bodies with gene activation during cerebellar granule neuron maturation.

Debarshi Mustafi

University of Washington, WA·Genetics·Early-career

Use targeted long-read sequencing of RB1 DNA and methylation from a patient's sample alone to assign the parent of origin of the inherited variant, and link it to retinoblastoma severity, treatment response and second-cancer risk.

X. Shawn Liu

Columbia University, NY·Neuroscience

Test whether reactivating the healthy MECP2 copy on the silenced X chromosome, by removing promoter methyl tags with dCas9-Tet1, rescues Rett syndrome symptoms in female mouse models.

The school

Washington University in St Louis: 97 labs on PI Pages, $1.2B a year on research, 365 research doctorates a year.

More about Washington University in St Louis

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