I work in Professor Janine LaSalle’s lab which focuses on genetic and epigenetic factors in human autism-spectrum disorders (ASDs). The LaSalle lab’s research focuses primarily on the MeCP2 protein and its role in the regulation of gene expression and chromosome organization. The gene for MeCP2 is located on the X-chromosome and is mutated in a number of neurodevelopmental disorders. Mutations in the MeCP2 gene cause Rett (RTT) syndrome, a devastating ASD that manifests almost exclusively in females and is characterized by a normal early development with a regression in development between the ages of 6-18 months of age.

I am investigating dynamic changes in neuronal maturation and MeCP2 throughout development and following neuronal activity, functional roles of each MeCP2 isoform using siRNA technology, and MeCP2 isoform-specific targets. It is hypothesized that the sub-nuclear localizations of MeCP2 isoforms are important for their functions in gene regulation. My preliminary data shows that neuronal activity dynamically regulates nuclear morphology, neuronal maturity, and the fluorescent intensity of MeCP2. The study of Rett syndrome, and more specifically the MECP2 gene and gene products, can allow for the development of therapies that can treat or compensate for the loss of MeCP2 function seen in RTT and provide hope for those who are suffering with this devastating disorder. In addition, my study may provide insight into other autism spectrum disorders.

Publications:

Articles:

H. Hirase, J. Creso, M. Singleton, P. Bartho, G. Buzsaki. 2004. Two-Photon Imaging of Brain Pericytes In Vivo Using Dextran Conjugated Dyes, Glia, 46 (1): 95-100

Abstracts:

M.K. Singleton, D.H. Yasui , Y. Gwye, K.N. Thatcher, A. Kumar, N.C. Schanen, J.M. LaSalle 2008. Activity-dependent changes in MeCP2 sub-nuclear localization. Abstract for oral presentation, 7th annual International Meeting for Autism Research (IMFAR), London, UK.

M. K. Singleton, D. H. Yasui, Y. Gwye, K. N. Thatcher, A. Kumar, N. C. Schanen, J. M. LaSalle. Activity-dependent changes in MeCP2 sub-nuclear localization. Society for Neuroscience abstract, 2007.

H. Hirase, J. Creso, M. Singleton, G. Buzsaki. Capillary Level Imaging of Local Cerebral Blood Flow in Bicuculline Induced Epileptic Foci. Program No. 429.6 2004 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience, 2004. Online.

H. Hirase, L. Qian, J. Creso, M. Singleton, P. Bartho, I. Creese, G. Buzsaki. Two-Photon Imaging of Astrocytes Using Calcium Sensitive Fluorescent Proteins In Vivo During Epileptic Events. Epilepsia 44 Suppl. 9: 33 (Abst. 1.085), 2003

H. Hirase, L. Qian, M. Singleton, I. Creese, G. Buzsaki. Two-Photon Imaging of Astrocytes Using Calcium Sensitive Dye and Virus-delivered Fluorescent Proteins In Vivo. Program No. 378.7. 2003 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience, 2003. Online.

H. Hirase, J. Creso, M. Singleton, G. Buzsaki. Relationship Between Neuronal Activity and Deep Microcapillary Hemodynamics Studied by 2PLSM in Mouse Neocortex In Vivo. Program No. 579.13. 2002 Abstract Viewer/Itinierary Planner. Washington, DC: Society for Neuroscience, 2002. Online.