This proposal describes a 5 year training program for the development of a clinician-scientist career in Stem Cell Biology and Nanotechnological Medicine. The principal investigator is now an assistant professor at Northwestern University where he will expand upon his scientific skills through a unique integration of interdepartmental resources. This program will improve outcome of current technology in a cochlear implant and it would ultimately benefit the 275 million deaf people worldwide for restoring their hearing. John Kessler, M.D. will mentor the principal investigators'scientific development. Dr. Kessler is a recognized leader in the field of stem cell neurobiology. He is the director of Stem Cell Biology Institute at Northwestern University and has trained numerous postdoctoral fellows and clinician-scientists. To enhance the training, the program will enlist the expertise of Dr. Samuel Stupp, Director of Institute of BioNanotechonology in Medicine (IBNAM) at Northwestern University. Dr. Stupp pioneered the Nanotechnological application in medicine. In addition, Dr. Stefan Heller at Stanford University, who is a leading scholar in hair-cell regeneration, will also provide scientific and career advice. The proposed study will integrate our current understanding of auditory neuron regeneration. The PI will first establish a method for the controlled generation of functional human embryonic stem cell (hESCs)-derived auditory neurons using diffusible ligands and overexpression of relevant human transcription factors. Having established this goal, The PI will then develop an appropriate stem cell niche for hESC-derived auditory neurons using a combined biophysical and biochemical approach involving nanotechnology and neurotrophic factors. The PI has the great fortune to be situated at a unique institute at Northwestern University, where both a human Pluripotent Stem Cell (hPSC) core facility and one of the largest bionanotechnology communities in the world co- exist in one academic institute. It is access to this technology and the support of PI's mentors, which makes this proposed work feasible. Department of Otolaryngology-Head and Neck Surgery Northwestern University provides an ideal setting for training clinician-scientists by incorporating expertise from diverse resources into customized programs. Such an environment maximizes the potential for the principal investigator to establish a scientific niche from which an academic career can be constructed.

Public Health Relevance

Successful controlled regeneration of spiral ganglion neurons with human embryonic stem cells would immediately allow us to re-program human induced pluripotent stem cells, which can be readily harvested from a patient's skin without any ethical concerns. With the provision of an appropriate stem cell niche by neurotrophic factors and nanofiber gel matrix, the human induced pluripotent stem cells can be transplanted into human cochlea to regenerate auditory neurons in the near future.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Clinical Investigator Award (CIA) (K08)
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Special Emphasis Panel (ZDC1)
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Sklare, Dan
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Northwestern University at Chicago
Schools of Medicine
United States
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Matsuoka, Akihiro J; Sayed, Zafar A; Stephanopoulos, Nicholas et al. (2017) Creating a stem cell niche in the inner ear using self-assembling peptide amphiphiles. PLoS One 12:e0190150
Matsuoka, Akihiro J; Morrissey, Zachery D; Zhang, Chaoying et al. (2017) Directed Differentiation of Human Embryonic Stem Cells Toward Placode-Derived Spiral Ganglion-Like Sensory Neurons. Stem Cells Transl Med 6:923-936
Newlands, Shawn D; Wei, Min; Morgan, David et al. (2016) Responses of non-eye-movement central vestibular neurons to sinusoidal yaw rotation in compensated macaques after unilateral semicircular canal plugging. J Neurophysiol 116:1871-1884