Alain Dabdoub Ph.D.

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Cross-Species Epigenetics

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Cross-Species Epigenetics
Tatjana Piotrowski, Ph.D. (chair), Stowers Institute for Medical Research
Alain Dabdoub, Ph.D., Sunnybrook Research Institute
Andy Groves, Ph.D., Baylor College of Medicine
Stefan Heller, Ph.D., Stanford University
The Lab of Neil Segil, Ph.D., University of Southern California
Litao Tao, Ph.D., Creighton University

This group will complete the collection of transcriptomic and epigenetic data from systems that regenerate (neonatal mouse, zebrafish, chick) and those that do not (mature mouse and human). In addition, they will begin to perform cross-species comparisons of the behavior of a shared set of hair cell loci across species. Collection of chick data is spearheaded by the Heller lab; the Groves, Segil, and Tao labs are responsible for mouse data; the Piotrowski lab leads work on zebrafish; and the Dabdoub lab will add data from humans. High-quality single-cell RNA-seq, ATAC-seq, and SHARE-seq data from multiple timepoints and conditions will be generated by all member labs.

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Establishing the Human Utricle from Surgical Patients as a Translational in Vitro Model for Hair Cell Regeneration

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Establishing the human utricle from surgical patients as a translational in vitro model for hair cell regeneration
Alain Dabdoub, Ph.D. University of Toronto
Stefan Heller, Ph.D. Stanford University
Michael Lovett, Ph.D. Imperial College London

These investigators will work with human utricles harvested during surgery to examine whether the response of human inner ear tissue to damage is similar to that of our mammalian model, the mouse. They will culture human utricles for extended lengths of time following damage with aminoglycoside drugs and determine whether the utricles show any proliferation of their supporting cells (making new supporting cells) or regeneration of their hair cells (making new hair cells). Mouse utricles have a limited ability to show proliferation and regeneration, and it is important to determine whether they are a good model for humans. The investigators also intend to examine gene expression in these human utricles to determine the molecular similarity of the cells of interest to their human counterpart cells.

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Growing Supporting Cells in Culture: Toward High-Throughput Screens

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Growing supporting cells in culture: toward high-throughput screens
Alain Dabdoub, Ph.D. University of Toronto
Andy Groves, Ph.D. Baylor College of Medicine
Neil Segil, Ph.D. University of Southern California

There is now a need for experimental systems to quickly test the candidates identified in Phase I experiments before moving into animal models and ultimately clinical trials. These researchers will develop a supporting cell culture system that can be used to quickly screen for factors that promote supporting cell growth or that promote supporting cells to generate hair cells. They will then test if this system can be used to grow cells at low density (allowing fewer cells to be used), to grow cells from older animals (necessary for a real drug), and to grow cells from the adult mouse utricle (which already shows limited regeneration). This project may give us the assay system needed to identify small molecule or gene therapeutics.

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