Amanda Whipple

Amanda Whipple

Assistant Professor
Department of Molecular and Cellular Biology
Amanda Whipple Photo
Studying RNA chemical modifications that are guided by imprinted non-coding and how differences in the three-dimensional folding of the two parental genomes in offspring impacts imprinted expression and neurodevelopment.

Our DNA represents the full library of genetic information each of us inherits from our parents. We inherit two copies of each gene, one from our mother and one from our father. Typically, the two copies are treated equally in the cell. However, my lab studies a unique class of “imprinted genes,” in which only one parental copy is active (“expressed”) while the other is inactive (“silenced”). Genomic imprinting is a phenomenon that occurs in cells in which a molecular mark distinguishes the gene copy inherited from one‘s mother versus one‘s father. Imprinted genes are unique because only one of the two parental copies are expressed or ‘on‘ while the other copy is ‘off‘. This type of parent-specific gene regulation has an immense impact on health and disease.

Imprinted genes are highly expressed in the brain and regulate many neurophysiological processes, including organismal behavior, cognition, socialization, and energy homeostasis. While concerted efforts have been made to delineate the functions of imprinted protein-coding genes, my lab seeks to discover new mechanisms by which parental genomes influence neuronal function by studying the activities of imprinted non-coding RNAs. We use computational and molecular approaches to understand why non-coding RNAs evolved imprinted expression in the brain, how imprinted non-coding RNAs function in neurons, and how dysregulation of imprinted non-coding RNAs contributes to disease.

We previously demonstrated that reduction of an imprinted long non-coding RNA is a viable therapeutic strategy for Angelman syndrome, a neurodevelopmental disorder caused by genetic loss of a maternally-expressed gene. This study serves as a paradigm for how fundamental discoveries of long non-coding RNA regulation can be translated to novel therapeutic strategies for imprinted disorders. We seek to expand on this work by examining the molecular mechanisms by which non-coding RNAs shape neuronal function.

Contact Information

Biological Laboratories Building, Room 4005B
16 Divinity Avenue,
Cambridge, MA 02138

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