Harvard Medical School
Degree: Doctor of Philosophy
One component of my work focuses on the functional properties of mature neurons from
the salamander and primate retina. These are neurons that have completed their neuroanatomical
differentiation in the animal. The general approach is to isolate cells following
enzymatic treatment of tissue and to use the characteristic morphology of cells to
identify them. Our main experimental approaches are electrophysiology and optical
imaging. We have studied phototransduction, synapse formation among the classes of
retinal cells and the ionic conductances and their compartmentalization in identified
cells. To improve the poor adhesion of mature neurons to conventional substrates,
we have immobilized select antibodies that target cell surface antigens to coverslips
to promote cell adhesion.
A second component focuses on the ability of adult newts to regenerate a new retina from retinal pigment epithelial (RPE) cells. Enucleation of an eye followed by re-implantation leads to retinal degeneration and to the generation of a new retina through a series of steps involving RPE cells. The steps include the depigmentation of the RPE cells followed by proliferation and differentiation of RPE-derived cells into an intact retina. Our aim is to determine the conditions that support retinal regeneration in vitro to help identify the cellular and molecular events that control the retinal regenerative process.
O’Brien, J.J., Chen, X., MacLeish, P.R., O’Brien, J. and Massey, S.C. Photoreceptor Coupling Mediated by Connexin 36 in
the Primate Retina. J. Neuroscience 32:4675-4687, 2012.
Young, A., Machacek, D.W., Dhara, S.K., MacLeish, P.R., Benveniste, M., Dodla, M.C., Sturkie, C.D. and Stice, S.L. Ion channels and ionotropic receptors in human embryonic stem cell derived neural progenitors. Neuroscience 192: 793-805, 2011.
Ford, G.D., Ford, B.D., Steele, E.C. Jr., Gates, A., Hood, D., Matthews, M.A., Mirza, S., MacLeish, P.R. Analysis of Transcriptional Profiles and Functional Clustering of Global Cerebellar Gene Expression in PCD3J Mice. Biochem. Biophys. Res. Commun. 2008 Oct 16, PMID: 18930027.
MacLeish, P.R. and Nurse, C.A. Ion channel compartments in photoreceptors: Evidence from salamander rods with intact and ablated terminals. J. Neurophysiology 98: 86-95, 2007.
Honors and Awards
Member, Dana Alliance for Brain Initiatives
Member, Institute of Medicine of the National Academies
Member, NIH BRAIN Working Group