ABSTRACT
Following traumatic injury to the adult central nervous system (CNS), neural connectivity is lost and fails to spontaneously regrow. This regeneration failure may be due to an intrinsic inability for damaged neurons to regrow in the adult as well as the formation, and persistence, of a lesion that is devoid of essential axon growth cues. My work is focused on using bioengineered tools (Biomaterials, AAVs, and neural progenitor cells (NPC)) to address these sources of regeneration failure so as to stimulate and chronically support neural circuit repair. The first part of the talk will outline new biological characterizations of the unique multicellular foreign body response (FBR) to biomaterials observed in the CNS and how various biomaterials properties can be manipulated to improve the functionality of these tools in bioengineered neural repair strategies. The second part of the talk will outline how we have used these biomaterial tools in combination with AAVs to stimulate axons to regrow after injury by the sequential re-activation of neuronal growth capacity and the reintroduction of essential molecular factors not present in CNS lesions. The last part of the talk evaluates the application of NPC grafts to CNS injury and outlines gains and remaining challenges in directing the differentiation of these grafts into specific neural cell phenotypes in vivo to provide long-term support to stimulated axon regeneration paradigms.
BIOGRAPHY
Dr. Timothy O’Shea is a Postdoctoral Fellow in Neurobiology at UCLA. He completed his PhD study in Medical Engineering and Medical Physics within the collaborative Health Sciences and Technology program of the Harvard Medical School and the Massachusetts Institute of Technology. Tim conducted PhD thesis research with Institute Professor Robert Langer developing injectable biomaterials to improve the delivery of reparative therapies for the treatment of various central nervous system (CNS) diseases. At UCLA he works with Professors Michael Sofroniew (Neurobiology) and Timothy Deming (Bioengineering) developing and testing novel bioengineering tools to study biological mechanisms involved in CNS injury and repair as well as the CNS FBR to biomaterial implants. His work has been supported by prestigious research fellowships from the Sir John Monash Foundation, the Society of Chemical Industry, the Craig H. Neilsen Foundation, Paralyzed Veterans of America, Wings for Life Foundation and the American Australian Association.
