Damon Page, Ph.D.
Ph.D., University of Cambridge (Medical Research Council Laboratory of Molecular Biology), 2002
Department of Neuroscience
The Scripps Research Institute
130 Scripps Way C341
Jupiter, Florida 33458
My laboratory is focused on understanding how the components that make up the cellular architecture of the brain (neuronal and glial cell types) are generated and assemble into functional circuits that underlie behavior and cognition. The mechanisms by which these processes occur are largely unknown, and yet, disruptions can have enormous societal and personal consequences in the form of neurodevelopmental and psychiatric disorders. Such disorders provide a window into the basic genetic, molecular and cellular mechanisms involved in building the brain. This insight may be used in turn to benefit those affected by mental illness, pointing to molecular targets for improved diagnostics and therapeutics.
Autism spectrum disorder (ASD) is one such disorder. ASD is characterized by a range of phenotypes, including deficits in social behavior, as well as an altered trajectory of brain growth in some cases. Clues to mechanisms come from reports that PTEN-PI3K-mTOR, monoamine, neuropeptide and synaptic signaling pathways have been implicated in ASD pathogenesis. Understanding how these risk factors influence brain and behavior will give us basic insight into how the brain develops and how this process is altered in ASD.
Along these lines, my laboratory makes use of transgenic and knockout mice to understand the biology of how risk factors for autism and related neurodevelopmental disorders influence the development of cell types and circuits underlying behavior and cognition, and to test efficacy of potential therapeutics. The development of structural and functional connectivity in the cerebral cortex, the seat of our highest cognitive capabilities and a structure that is highly relevant for autism, is a major area of focus for our work.
We use a variety of techniques, including mouse genetics, histology, molecular cell biology, cell culture, genomics, informatics, pharmacology, imaging and behavioral phenotyping.
Huang W-C, Chen Y, & Page DT. (2016) Hyperconnectivity of medial prefrontal cortex-amygdala circuitry in a mouse model of macrocephaly/autism syndrome. Nature Communications (In Press)
Huang W-C, Abraham R, Shim B-S, Choe H & Page DT. (2016) Zika virus infection during the period of maximal brain growth causes microcephaly and corticospinal neuron apoptosis in wild type mice. Scientific Reports 6, 34793.
Clipperton-Allen AE, Chen Y and Page DT. (2016) Autism-relevant behaviors are minimally impacted by conditional deletion of Pten in oxytocinergic neurons. Autism Research online DOI:10.1002/aur.1641
Swarnkar S, Chen Y, Pryor WM, Shahani, N, Page DT, Subramaniam S. (2015) Ectopic expression of the striatal-enriched GTPase Rhes elicits cerebellar degeneration and an ataxia phenotype in Huntington's disease. Neurobiology of Disease 82, 66-77.
Sejourne J, Llaneza D, Kuti OJ and Page DT. (2015) Social Behavioral Deficits Coincide with the Onset of Seizure Susceptibility in Mice Lacking Serotonin Receptor 2c. PLOS One, DOI:10.1371/journal.pone.0136494.
Chen Y, Huang WC, Sejourne J, Clipperton-Allen, AE and Page DT. (2015) Pten Mutations Alter Brain Growth Trajectory and Allocation of Cell Types through Elevated β-Catenin Signaling. Journal of Neuroscience 35, 10252-10267.
Clipperton-Allen AE and Page D. (2015) Decreased aggression and increased repetitive behavior in Pten haploinsufficient mice. Genes, Brain and Behavior. 14, 145-157.
Pryor W, Biagioli M, Shahani N, Swarnkar S, Huang WC, Page DT, MacDonald M and Subramaniam S (2014) Huntingtin promotes mTORC1 signaling in the pathogenesis of Huntington’s disease. Science Signaling 7 (349): ra103
Aceti M, Creson TK, Vaissiere T, Rojas C, Huang W-C, Wang Y-X, Petralia RS, Page DT, Miller CA, Rumbaugh G. (2014) Syngap1 Haploinsufficiency Damages a Postnatal Critical period of Pyramidal Cell Structural Maturation Linked to Cortical Circuit Assembly. Biological Psychiatry 77, 805-815.
Clippterton-Allen, AE and Page, DT (2014) Pten haploinsufficient mice show broad overgrowth but selective impairments in autism-relevant bahavioral tests. Human Molecular Genetics, 23: 3490-3505.
Awards, Recognition, Appointments, and Honors
1999 Medical Research Council Laboratory of Molecular Biology/Peterhouse Research Studentship
2002 Max Perutz Research Student Prize (MRC LMB)
2004 Fellowship from the Nancy Lurie Marks Family Foundation
2006 Investigator, Autism Consortium
2010 Mentor of Intel Science Talent Search national finalist