Nanomaterials to improve growth factor delivery to the cornea - This proposal describes a 3-year mentored career development plan to foster a transition to research independence in the fields of ocular biomaterials and drug delivery. The candidate, Levi N. Kanu, M.D., is an Instructor in Ophthalmology at Harvard Medical School, an Investigator at Schepens Eye Research Institute, and a practicing cornea specialist at Mass Eye and Ear. The proposed career development plan will be conducted in the enriching environments of the Harvard community, including Schepens Eye Research Institute, Mass Eye and Ear, and the Harvard School of Engineering. His background includes scientific training in chemical engineering, medical devices, drug delivery, cell culture, animal models, and clinical and surgical management of ocular diseases. His long-term goals are to become a thought leader in his area of research and to make important advances in the treatment options for patients with ocular diseases. This proposal outlines a comprehensive plan to achieve scientific independence through 1) systematically investigating novel techniques for ocular protein delivery, 2) refining grantsmanship skills, 3) developing leadership and managerial skills, and 4) fostering early career collaborations. Dr. Kanu’s proposal includes regular educational seminars, structured coursework, regular meetings with expert mentors, and clearly defined milestones. The advisory committee will include the following: 1) Primary Mentor Dr. Joseph Ciolino, an expert in ocular drug delivery; 2) Co-mentor Dr. Reza Dana, a scientific leader in corneal disease with extensive clinician-scientist mentorship experience; 3) Collaborator Dr. David Mooney, a renowned expert in biomaterials and drug delivery; and 4) Collaborator Dr. Dimitrios Karamichos, an expert in corneal biology and wound healing. The proposed basic and translational research plan will be conducted primarily at Schepens Eye Research Institute and aims to address the challenges associated with therapeutic protein delivery to the cornea. Specifically, Dr. Kanu will study the feasibility of a novel nanocomposite hydrogel to achieve sustained and localized nerve growth factor-delivery to the ocular surface as a treatment for diabetic keratopathy, since effective treatments for this condition are currently lacking. Dr. Kanu will perform the following investigations: 1) study the effects of physicochemical nanoparticle properties on nerve growth factor-release kinetics and epithelial cell interactions of a nanocomposite hydrogel; 2) study the effect of continuous nerve growth factor exposure on corneal epithelial cell receptor activation and consequent cell functions; and 3) study the effects of continuous nerve growth factor exposure on diabetic corneal epithelium and nerves using in vitro and in vivo models of diabetic keratopathy. The proposed research may lead to improved methods to efficiently deliver proteins to the ocular surface. Both the proposed technology and the systematic approaches may be adapted to other large molecule therapies. Finally, findings from this research may provide scientific evidence to support a clinical trial and will form the basis of an R01 application by the end of the K08 award period.
