By Lisa Goodrich, Ph.D.
Regular readers will know that Hearing Restoration Project members are incredibly adept at collaborating virtually thanks to Zoom, the gEAR data platform, and a number of other tools. But there is something really special about getting everyone together in person in one place.
Earlier this year the entire HRP consortium gathered in Salt Lake City for our annual meeting—the first such meeting to be held in person since the COVID pandemic. I relished the chance to spend dedicated time with this group of amazing scientists away from our everyday responsibilities at our home institutions. This kind of personal interaction leads to different types of discussions and has been sorely missed over the past few years!
At the same time, the consortium is more than its principal investigators (PIs)—each member has a team of exceptional graduate students, postdoctoral researchers, and lab technicians who are absolutely central to the experiments and data collection that need to be done every day. Logistics and funding mean that only the PIs can attend the HRP annual meeting in person, but we all agreed that it would be more successful and impactful if we could include our teams.
This is why the majority of the first day of our two-day meeting was hybrid, with lab members joining from our respective 14 institutions to hear updates from each of the three working groups and discuss the data presented. This went a long way toward creating a sense of community that is essential for the kind of uniquely collaborative work we are doing.
The second day was dedicated to discussion among the PIs on the current status of working groups’ plans, the path forward, and the joint article that will be submitted to a journal by the end of this year. We all learned a lot from one another, identified ways to improve our integrated analysis, and were able to go home with new ideas and renewed vigor.
The annual meeting provides a valuable opportunity for us to look at the data as a consortium and think about both what this data is telling us and what our next steps are. One of the huge benefits of being in the consortium is having the opportunity to share our findings with people who are part of the same mission, yet have their own unique perspectives and deep wells of expertise.
Taking the time to look at the big picture together helps us identify roadblocks and also opportunities. Because the HRP meets frequently as a full group and as working groups, each lab is able to remain flexible and pivot if and when results indicate a better direction, knowing that we can leverage each other’s expertise, reagents, and tools.
Since its beginnings, the HRP has been guided by a three-phase strategic plan. While some of the details have changed over the years (as should be expected), the overall path has remained fairly constant. The first phase or goal is cataloging gene expression across the three primary species: zebrafish, chick, and mouse. We remain convinced that by comparing genes and the regulation of those genes, as well as comparing these in species and systems where hair cells regenerate and where they do not, that we can identify genetic pathways and targets that we might be able to use to encourage the events we aim to stimulate.
The second goal is figuring out what happens when we manipulate these pathways in an adult mammalian cochlea, which cannot naturally regenerate hair cells on its own. One of the working groups has begun to do exactly this and the results suggest we are on the right path, though we still have a ways to go.
In fact, an important part of this work is testing potential mechanisms to identify where they stop working. Each step forward puts us in a position where we can go back and do it better in the next attempt. The third goal, and we’re not quite there yet, is to use all of this information to design drugs that have the effect we want: to regenerate viable hair cells in the human inner ear.
And the fourth goal guiding the group is how the HRP helps the entire ear field. Science is collaborative. We demonstrate that in our consortium model, but we want this collaborative spirit to extend beyond our labs. Through data sharing, training the next generation of scientists, and building tools that are being used by colleagues around the world, the HRP is having a positive impact far beyond the consortium itself. The challenge we are tackling is complex, and the more people working on it, and the more information they have available to them, the faster we as a field can move toward resolving that challenge.
The collaborative spirit of our consortium is especially evident as we work together to complete a publication describing our analysis of hair cell gene expression. This will be the first all-member joint publication by the HRP and is a significant milestone. We will share with the entire field a meta-analysis of genes that are expressed in 28 different kinds of hair cells—from both auditory and vestibular organs, in four species, and at many stages of development.
To do this, we figured out a way to compare data that was collected from different species and using different methods. This required first determining how to identify the same gene across species and then to devise a reliable metric for whether that gene is expressed at higher levels in each hair cell relative to its surrounding supporting cells.
This has been a complex process, and we will share the methodology and results with our colleagues. With these data, labs across the world can compare the data they generate in their own labs to the HRP’s to see, for example, how a gene they have identified in one animal model acts in any of the species we used and whether that gene might be a good target for future therapies.
As well as sharing what we have learned in the article, we will make these data even more accessible on the gEAR, our data sharing and visualization tool that removes technical and coding difficulties to allow anyone to conduct incredibly simple and quick analyses.
This most recent annual meeting allowed us to step back and appreciate just how far the consortium has come over the past decade. It is hard to convey the excitement in the group in an article like this, but there is a collective feeling that we are entering a new phase in the HRP’s work.
As is typical in this kind of ambitious endeavor, we have spent years figuring out what kind of data we need to see and how to get it. Now, we are looking at that data and seeing evidence of the effects we are hoping to be able to control. We have not reached the ultimate goal of regenerating human inner ear hair cells but, more than ever, we know we are on the right path.
HRP scientific director Lisa Goodrich, Ph.D., is a professor of neurobiology at Harvard Medical School. This appeared in the Summer 2023 issue of Hearing Health magazine, whose cover story features HRP member and Emerging Research Grants scientist Ronna Hertzano, M.D., Ph.D.
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Our results suggest that mature cochlear supporting cells can be reprogrammed into sensory hair cells, providing a possible target for hair cell regeneration in mammals.