Budd A. Tucker, Ph.D.

Education

2001-2006    Ph.D.        Neuroscience, Memorial University of Newfoundland

1996-2001    B.A.H.         Sir Wilfred Grenfell College

Awards

• 2006-2008, Post-Doctoral Fellowship (PDF), NSERC, Government of Canada

• 2006, Summer Fellowship, Marine Biological Laboratories, Research Award, Fundamental Issues in Vision Researc

• 2006, Fellow of the School of Graduate Studies

• 2004-2006, Canadian Graduate Scholarship Doctoral (CGSD), NSERC, Government of Canada; Awarded to the top post-graduate scholarship (PGS) doctoral candidates across the country

• 2001-2006, Graduate fellowship, Institutional fellowship, Memorial University of Newfoundland

• 2002-2004, Postgraduate Scholarship (PGSB), NSERC, Government of Canada

• 2001-2002, School of Graduate Studies Fellowship, Institutional fellowship, Memorial University of Newfoundland

• 2000-2001, Research scholarship, Institutional scholarship, Sir Wilfred Grenfell College

• 2000, Millennium scholarship, Provincial scholarship, Newfoundland, Canada

• 1996, Entrance scholarship, Institutional scholarship, Sir Wilfred Grenfell College

Research Project

Unlike the peripheral nervous system, the regenerative capacity of the adult mammalian central nervous system is limited, due in part to the formation of an injury-induced glial scar.  The glial scar is a structure that forms during reactive gliosis, in which reactive glial cells form a dense fibrotic barrier that contains a variety of inhibitory extracellular matrix molecules.  These molecules include the chondritin sulfate proteoglycans (CSPGs) and the glycoprotein CD44, both of which function as chemical inhibitors to axon growth, thus preventing regeneration.  Like the brain and spinal cord, the retina, a part of the central nervous system, is not exempt from these growth inhibitory processes.  For example, the C3H-rd1 mouse, which undergoes rapid degeneration of the photoreceptor layer, is plagued by the formation of a glial scar and the deposition of CD44 and various CSPGs at the outer limits of the remaining retina.  Therefore, retinal transplantation, which attempts to induce regeneration, has failed, in part due to the presence of these inhibitory molecules.  Thus, my current research is focused on the removal of the inhibitory extracellular matrix (ECM)/glial barrier and the induction of retinal regeneration via healthy donor cell transplantation for the treatment of blinding eye diseases, such as retinitis pigmentos and age related macular degeneration.  Two specific strategies are being utilized:  1) stem cell transplantation and 2) drug delivery via biodegradable polymers, both of which center around the ECM degrading enzymes, matrix metalloproteinases (MMPs).  MMPs have the ability to digest a range of bioactive extracellular matrix molecules including the CSPGs and CD44.  For instance, our recent study utilized the transplantation of retinal progenitor cells and showed that increased MMP2 secretion from activated muller glia result in the proteolysis of CD44 and neurocan (a CSPG) in the degenerated retina, thereby producing a more permissive environment for regeneration while enhancing transplant integration.  Thus, new strategies are focused on the delivery of retinal stem cells and active MMP2 to sites of injury via biodegradable polymers, giving controlled precise release and degradation of glial scar proteins, while stimulating new photoreceptor production or donor cell integration.

Selected Publications

1. Tucker, B.A. Chen, D.F., Yang, L. and Young, M.J. Elevated matrix metalloproteinases expression in the retina of the healer mouse creates a permissive environment for retinal regeneration.  IOVS, submitted 2007.

2. Tucker, B.A., Rahimtula, M., and Mearow, K. M. Src and Fak are key early signaling intermediates required for neurite growth in NGF-responsive adult DRG neurons.  Cellular signaling, submitted 2007.

3. Zhang, Y., Klassen, H.J., Tucker, B.A., Perez, M.T., and Young, M.J. (2007).  CNS progenitor cells promote a permissive environment for neurite outgrowth via a matrix metalloproteinase-2-dependent mechanism.  Journal of Neuroscience, 27(17):4499-506.

4. Ploughman, M., Granter-Button, S., Chernenko, G., Attwood, Z., Tucker, B.A., Mearow, K.M., and Corbett, D. (2007).  Effects of acute exercise on growth factors involved in neuronal plasticity following focal ischemia.  Brain Research, 1150:207-16.

5. Tucker, B.A., Rahimtula, M., and Mearow, K.M. (2006).  Sub-populations of dorsal root ganglion neurons respond differently to integrin and growth factor receptor stimulation: Identifying potential targets for the treatment of peripheral neuropathies.  European Journal of Neuroscience, 24(3): 676-90.

6. Tucker, B.A., Rahimtula, M., and Mearow, K.M. (2005).  A procedure for selecting and culturing sub-populations of cells from a heterogeneous pool of DRG neurons by the use of antibody coated magnetic beads.  Brain Research, 16: 50-57

7. Ploughman, M., Granter-Button, S., Chernenko, G., Tucker, B.A., Mearow, K.M., and Corbett, D. (2005).  Endurance exercise regimens induce differential effects on BDNF, synapsin-I and IGF-I after focal ischemia.  Neuroscience. 136 (4): 991-1001.

8. Tucker, B.A., Rahimtula, M., and Mearow, K.M. (2005).  Integrin activation and neurotrophin signalling cooperate to enhance neurite outgrowth in sensory neurons. Journal of Comparative Neurology. 486 (3): 267-280.

9. Jones, D.M., Tucker, B.A., Rahimtula, M., and Mearow, K.M. (2003).  The synergistic effects of NGF and IGF-1 on neurite growth in adult sensory neurons: Convergence on the PI 3-kinase signaling pathway. Journal of Neurochemistry. 86: 1116-1128.