The Gubbels Laboratory
Faculty Samuel P. Gubbels
Samuel P. Gubbels
Assistant Professor, Department of Surgery, Division of Otolaryngology
Organ System/Disease Focus
Inner ear, Hearing loss
Aligned Research Focus
Regenerative medicine for hearing loss, Hair cell regeneration, Inner ear stem cell transplantation, Adult cochlear stem cells
Research Description
Hearing loss is an exceedingly common problem worldwide with severe to profound deafness affecting 278 million people worldwide. In general, hearing loss in humans is caused by loss or dysfunction of the hair cells of the cochlea and, when lost, these cells cannot spontaneously regenerate which leads to the permanency that typifies the clinical course of most cases of deafness. While the current treatments for hearing loss, hearing aids and cochlear implants, work very well, they do have some drawbacks. The ideal treatment for hearing loss would be to replace the elements of the inner ear which have been lost due to loud noise, ageing, ototoxic medications, or hereditary causes.
My lab is interested in using a variety of pluripotent stem cell types to model the development, disease and regeneration of inner ear hair cells in vitro. In collaboration with the laboratory of Dr. Su-Chun Zhang, we are actively defining a method to reliably direct the differentiation of pluripotent stem cells into auditory hair cells and other inner ear cell types. In addition, we seek to evaluate the ability of these cells to integrate into the appropriate areas of the inner ear upon transplantation by using a novel, developmental in vivo model system. We believe that knowledge gained in these studies may provide important insight into how pluripotent stem cells can be used to model inner ear disease and realistically pursue cell-based therapies for hearing loss in the future.
Selected References
Gubbels SP, Woessner DW, Mitchell JC, Ricci AJ, Brigande JV. Functional auditory hair cells produced in the mammalian cochlea by in utero gene transfer. Nature, September 25, 2008; 455(7212): 537-542.
Brigande JV, Gubbels SP, Woessner DW, Jungwirth J, Bresee CS. Electroporation-Mediated Gene Transfer to the Developing Mammalian Inner Ear. Methods in Molecular Biology, 2009; 493:125-139.
Hildebrand MS, Newton SS, Gubbels SP, Sheffield AM, KocharA, de Silva MG, Dahl HH, Rose SD, Behlke MA, Smith RJ. Advances in Molecular and Cellular Therapies for Hearing Loss. Molecular Therapy, February 08; 16(2), 224-236.
Sheffield AM, Gubbels SP, Hildebrand MS, Newton SL, Chiorini JA, Di Pasquale G, Smith RJH. Viral Vector Tropism for Supporting Cells in the Developing Murine Cochlea. Hearing Research, 2011; 277(1-2):28-36. (PMCID – PMC3137760)