By Lisa Goodrich, Ph.D.
The Hearing Restoration Project consortium model has, since its start, centered on team science, collaboration, and the faster exchange of data. To further energize this approach and facilitate even closer interaction, including among HRP researchers’ postdoctoral researchers and other lab members, the HRP decided at its March 2021 annual meeting to reorganize its research into three working groups.
To facilitate even closer interaction, including among HRP researchers’ postdoctoral researchers and other lab members (such as in the Sunnybrook Research Institute lab of Alain Dabdoub, Ph.D., above), the HRP decided at its March 2021 annual meeting to reorganize its research into three working groups.
These groups are organized in line with the consortium’s three main goals. The Cross-Species Epigenetics working group compares gene expression and epigenetics across species to identify and describe the molecular mechanisms that prevent hair cell regeneration. The Integrative Analysis working group performs a meta-analysis of data collected from different species over the years and will curate the data available to access via the gEAR, the data sharing and data visualization tool developed with HRP funding. The third working group, Reprogramming and Gene Delivery, is charged with finding ways to stimulate hair cell regeneration by targeting supporting cells.
Starting this year, funding is being distributed to members of each group, all of whom contributed to the submission of one joint proposal for each working group and all of whom will be contributing in specific ways to achieving their respective working group’s aims and milestones. The work previously organized in individual projects will continue, including the multiyear Seattle Plan projects readers are familiar with, but the working group model fosters the addition of even more timely and synergistic collaboration.
Each consortium member belongs to at least one working group, and a total of $1.2 million is being distributed to HRP members for the new project year (Oct. 1, 2021, through Sept. 30, 2022).
Cross-Species Epigenetics
Neil Segil, Ph.D. (chair), University of Southern California
Alain Dabdoub, Ph.D., Sunnybrook Research Institute
Andy Groves, Ph.D., Baylor College of Medicine
Stefan Heller, Ph.D., Stanford University
Tatjana Piotrowski, Ph.D., Stowers Institute for Medical Research
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, starting with fish and mouse and adding chick data. The group will also add data from humans using a pipeline that is now in place.
Integrative Analysis
Seth Ament, Ph.D. (co-chair), University of Maryland
Ronna Hertzano, M.D., Ph.D. (co-chair), University of Maryland
Albert Edge, Ph.D., Mass Eye & Ear
Stefan Heller, Ph.D., Stanford University
David Raible, Ph.D., University of Washington
Jennifer Stone, Ph.D., University of Washington
Mark Warchol, Ph.D., Washington University in St. Louis
This group will take the lead on data curation and analysis. The HRP is adding a dedicated full-time HRP analyst to work across groups to help collect and process data, thereby facilitating a long-planned cross-species analysis. The group will start by annotating hair cell types from all species so that anyone in the field can assess what kind of hair cell their regeneration approaches may produce, while also easing identification of common hair cell genes, which will help the Cross-Species Epigenetics group. Analysis of the hair cells produced in mouse organoids will be performed as an example and to lay the groundwork for using organoids to screen genes in the future.
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
Neil Segil, Ph.D., 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. They will additionally work toward developing new methods to deliver molecules and/or genes, including endogenous activation of reprogramming factors via CRISPR/Cas-9.
HRP scientific director Lisa Goodrich, Ph.D., is a professor of neurobiology at Harvard Medical School. For more, see hhf.org/hrp.
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