Yehoash Raphael Ph.D.

Reprogramming and Gene Delivery

Reprogramming and Gene Delivery
Andy Groves, Ph.D. (chair), Baylor College of Medicine
John Brigande, Ph.D., Oregon Health & Science University
Yehoash Raphael, Ph.D., University of Michigan
Segil Lab, University of Southern California

This group will take the lead on transitioning to Phase II, testing candidate genes. They will study the effects of current transcription factor reprogramming cocktails on supporting cell behavior, including the collection of additional transcriptomic and epigenetic data that will be shared with the CSE group. These experiments will be performed in a variety of systems, including a flattened epithelium guinea pig model that shares features with chronic human deafness. The Groves lab will use transgenic mice to detail the effects of the reprogramming cocktails in the organ of Corti. The Brigande lab will continue its work on creating efficient mouse model systems to interrogate candidate genes for sensory hair cell regeneration, as pioneered by testing whether viral delivery of these same reprogramming factors is also efficacious. The Raphael lab will take a similar approach in the guinea pig model, in this case using a virus designed and generated by the Groves and Segil labs. These experiments are part of the group’s broader efforts to develop new methods to deliver molecules and/or genes, for example by endogenous activation of reprogramming factors via CRISPR/Cas-9.

Methods for Delivering Adenovirus Vectors to Non-Sensory Cells in the Deaf DTR Mouse Cochleae

Methods for delivering adenovirus vectors to non-sensory cells in the deaf DTR mouse cochleae
Yehoash Raphael, Ph.D. University of Michigan

The HRP is beginning to identify molecules that could modulate hair-cell regeneration, but introducing them into the mammalian inner ear is challenging. This project will develop methods using adenoviruses to deliver biomolecules into the mature mammalian cochlea. The methods used are designed to mimic a therapeutic approach.