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Assistant Professor of Molecular and Cellular Biology

Amanda Whipple

Assistant Professor of Molecular and Cellular Biology

Arriving summer 2019

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Gene Regulation in the Brain by Imprinted Non-coding RNAs

Genomic imprinting results in the preferential expression of a gene from either the maternal or paternal allele. Nearly all imprinted domains express non-coding RNAs, including both long and small non-coding RNAs, in a parental biased manner. Yet, the physiological functions and molecular mechanisms of these imprinted transcripts are poorly characterized. Our lab aims to determine the cis- and trans-acting mechanisms of imprinted, non-coding RNAs in the brain.

We have established an in vitro system that enables detection and manipulation of allele-specific expression in neurons. We are currently using this system to (1) identify the neuronal targets of orphan snoRNAs, (2) delineate the neuronal networks regulated by imprinted miRNAs, and (3) determine the mechanisms by which imprinted long non-coding RNAs repress genes in cis.

Imprinted disorders arise from inappropriate genetic alterations within imprinted domains. We have previously shown that targeting an imprinted long non-coding RNA is a viable therapeutic strategy for treatment of an imprinted disorder. In the future, we will perform additional studies to examine the physiological role of imprinted non-coding RNAs during normal and dysregulated neurodevelopment.

Selected Publications

  1. Fink JJ, Robinson TM, Germain ND, Sirois CL, Bolduc KA, Ward AJ, Rigo F, Chamberlain SJ, and Levine ES (2017) Disrupted neuronal maturation in Angelman syndrome-derived induced pluripotent stem cells. Nat Commun 8:15038. PMCID: PMC5413969
  2. d’Ydewalle C, Ramos DM, Pyles NJ, Ng SY, Gorz M, Pilato CM, King K, Kong L, Ward AJ, Rubin LL, Rigo F, Bennett CF, & Sumner CJ (2017) The antisense transcript SMN-AS1 regulates SMN expression and is a novel therapeutic target for spinal muscular atrophy. Neuron, 93(1):66-79. PMCID: PMC5223741
  3. Meng L*, Ward AJ*, Chun S, Bennett CF, Beaudet AL, & Rigo F (2015) Towards a therapy for Angelman syndrome by targeting a long non-coding RNA. Nature, 518(7539):409-12. PMCID: PMC4351819
  4. Ward AJ, Rimer M, Killian JM, Dowling JJ, & Cooper TA (2010) CUGBP1 overexpression in mouse skeletal muscle reproduces features of myotonic dystrophy type 1. Hum Mol Genet 19(18):3614-22. PMCID: PMC2928132

Note: In 2016 Ward was changed to Whipple