(provided by candidate): The goal of this application is to provide a supervised training program that will promote the candidate's development into an independent physician - scientist. This will be accomplished through a coordinated effort in the Department of Otolaryngology and the Interdisciplinary Stem Cell Institute (ISCI), at University of Miami. This proposal will enable the candidate to pursue his interest in mechanisms of regeneration in the olfactory system through a mentored plan to study nasal stem cells and specific signaling pathways. Research Program: Although olfactory neurons in the nose are replaced continually from progenitor or stem cells, certain conditions can lead to a loss of olfactory function that likly is a consequence of failures in this repair process. Anosmia can occur following head injury, prior upper respiratory infections, active sinusitis, or as a consequence of the aging process. There are currently no effective treatments for sensorineural anosmia. The broad, long term goals of this proposal are to develop novel treatments for anosmia. Our interest in determining mechanisms regulating olfactory progenitors has led to the novel finding that olfactory cells expressing the c-kit receptor can give rise to olfactory neurons. The central hypothesis of this proposal is that c-kit (+) progenitor cells serve a key role in adult olfactory maintenance. The experiments proposed here will directly define the role of nasal c-kit (+) progenitors in olfactory neurogenesis and regeneration under various conditions. Defining the function of specific nasal stem and progenitor cells underlying olfactory neuronal replacement, and determining their regulatory mechanisms, are essential steps towards the establishment of new treatments for anosmia. Training Program: The candidate will participate in a didactic program to enhance his career development. Courses and seminars at University of Miami relating to ethics, research design, and biostatistics will be audited. Also, he will participate in intellectual activities in he Otolaryngology Department and the Stem Cell Institute. Frequent meetings with advisors will be utilized to monitor progress. Dr. Josh Hare, ISCI Director, and Dr. Nirupa Chaudhari, Professor of Physiology and Biophysics, will serve as Mentors.

Public Health Relevance

of this proposed project is to develop potential treatments for the clinical problem of anosmia, for which there are currently no treatments. Olfactory impairment is estimated to affect at least 14 million older adults in the United States, and more than 200,000 visits are made to physicians each year for chemosensory complaints. The sense of smell contributes to one's safety, nutritional intake, and quality of life.

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-SRB-Y (56))
Program Officer
Rivera-Rentas, Alberto L
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University of Miami School of Medicine
Schools of Medicine
Coral Gables
United States
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Choi, Rhea; Goldstein, Bradley J (2018) Olfactory epithelium: Cells, clinical disorders, and insights from an adult stem cell niche. Laryngoscope Investig Otolaryngol 3:35-42
Goldstein, Bradley J; Choi, Rhea; Goss, Garrett M (2018) Multiple polycomb epigenetic regulatory proteins are active in normal and regenerating adult olfactory epithelium. Laryngoscope Investig Otolaryngol 3:337-344
Kurtenbach, Sarah; Ding, Wen; Goss, Garrett M et al. (2017) Differential expression of microRNAs among cell populations in the regenerating adult mouse olfactory epithelium. PLoS One 12:e0187576
Goncalves, Stefania; Goldstein, Bradley J (2016) Pathophysiology of Olfactory Disorders and Potential Treatment Strategies. Curr Otorhinolaryngol Rep 4:115-121
Goldstein, Bradley J; Goss, Garrett M; Choi, Rhea et al. (2016) Contribution of Polycomb group proteins to olfactory basal stem cell self-renewal in a novel c-KIT+ culture model and in vivo. Development 143:4394-4404
Goss, Garrett M; Chaudhari, Nirupa; Hare, Joshua M et al. (2016) Differentiation potential of individual olfactory c-Kit+ progenitors determined via multicolor lineage tracing. Dev Neurobiol 76:241-51
Goldstein, Bradley J; Goss, Garrett M; Hatzistergos, Konstantinos E et al. (2015) Adult c-Kit(+) progenitor cells are necessary for maintenance and regeneration of olfactory neurons. J Comp Neurol 523:15-31