Member: Hearing Restoration Project
Current Institution: National Institute on Deafness and Other Communication Disorders (NIDCD)
Education: Tel Aviv University, Sackler School of Medicine, B.Sc., M.D., and Ph.D.
What is your area of focus?
I am an otolaryngologist surgeon-scientist. My clinical practice focuses on the diagnosis and treatment of diseases of the ear, with an emphasis on hearing restoration. I see and treat patients with auditory and vestibular dysfunction (hearing loss and dizziness), including cochlear implantation, and dedicate the remainder of my time to research, where my goal is to make significant contributions toward the treatment of these conditions. In terms of hearing restoration, I work to unravel pathways that lead to the proper development of the ear, specifically the inner ear’s sensory hair cells.
Why did you decide to get in to scientific research?
I actually did not plan to be a scientist. In my first summer of medical school I did a research rotation in a cancer laboratory and it felt like the first time I went diving, discovering a new world. The next year, I looked for a laboratory that focused on genetics, as this was my favorite topic in medical school at Tel Aviv University. My mother is an audiologist and I used to visit the rehabilitation center for preschoolers who were deaf or hard of hear and their families on a regular basis. Karen Avraham, Ph.D., who studies the molecular basis of hearing loss using mouse models and human families with hereditary hearing loss, offered me a summer research position in her laboratory. That summer everything came together. I subsequently switched to the M.D.-Ph.D. track, completed a Ph.D. under the guidance of Dr. Avraham and other mentors, focusing of regulation of gene expression in the ear.
If you had not become a researcher, what would you have done?
I would have joined my family’s business, Rummikub. My grandfather, Efraim Hertzano, developed the tile-based game that combines elements from rummy, dominoes, mah-jongg, and chess when he immigrated to Israel from Romania, where card-playing had been outlawed. His children—my father and aunt—joined the business and turned Rummikub into a game that is now played in 26 languages and in more than 50 countries. I have worked in the company since I was a child, and still serve as a referee for the World Rummikub Championships, which takes place every three years.
What is the most exciting part of your research?
Mentorship. The laboratory consists of medical, audiology, undergraduate, graduate, and postdoctoral students, as well as research staff. The team is wonderful and the gift of being able to teach our students and provide a nourishing academic environment for them to experience research, grow, and become independent, is fulfilling. Of course, this is all fueled by ongoing discoveries—small steps that ultimately lead to better understanding of hearing and hopefully development of therapeutics.
What has been a highlight /memorable moment of your career?
During my residency training at the University of Maryland School of Medicine, I worked on a project (funded by Hearing Health Foundation’s Emerging Research Grants program) to detect fingerprints of regulatory genes in different cells in the ear. Our top candidate was a match to the binding site of a family of regulators called RFX. These were supposed to be important for the final differentiation of the sensory cells. The day we finally found the correct combination of RFX necessary for hearing was one of the most memorable moments of my career.
What do you enjoy doing when you are not in the lab?
Fitness has always played a great role in my life. I used to be a long and triple jumper in the Israeli youth and adult national teams, and then a combat fitness and self-defense instructor for the Israel Defense Forces. While I do not engage in these sports anymore, I enjoy long distance running, group road biking, and high interval training classes. Participating in sports on a regular basis is vitalizing, refreshing, and often times the best ideas come up during a run.
How does your research complement the HRP’s work?
Several years ago I realized that big data from what are called “-omics” experiments—which look at all of the genes (or proteins) that are expressed (or turned on) in a cell or tissue—are becoming more prevalent. The HRP uses a variety of -omics to compare sensory cell regeneration in ears of chick, fish (which do regenerate the sensory cells) and mice (which, like humans, do not). However, the files are so big and complex that while biologists are generating them they need computational scientists to access and interpret them.
On a run, I had an idea of how to turn big data into self-colorizing “cartoons,” where values of gene expression are represented as variations in color intensity—making it much easier to conceptualize than massive spreadsheet tables or even graphs. The tool is called the gEAR—gene Expression Analysis Resource. With funding from HHF donors, the HRP supports the gEAR, and the gEAR supports HRP scientists—while also using them as a focus group. This is a perfect relationship, allowing the gEAR to progress much faster than expected.
What has been a highlight from the HRP consortium collaboration thus far?
The HRP consists of a tremendous group of researchers that are all focused on curing hearing loss. Being able to interact with this diverse group of researchers, collaborate with them, and exchange ideas on a regular basis has been a true highlight. I learn something new every time we meet and hope that the tools we develop are beneficial for the groups.
What do you see is needed to help make HRP goals happen?
The HRP needs more funds and donations. These are the most important building brick right now, that is necessary to keep the experiments and collaborations going. The HRP has many more focused research proposals than funds to perform the research. The donations are what make research happen.
Integrative Analysis
Seth Ament, Ph.D. (co-chair), University of Maryland
Ronna Hertzano, M.D., Ph.D. (co-chair), National Institute on Deafness and Other Communication Disorders
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
This group will take the lead on data curation and analysis. A dedicated full-time HRP analyst is working across groups to help collect and process data, thereby facilitating a broader analysis of cell states and trajectories across species. 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. The Ament lab will leverage their expertise in bioinformatics, while the Hertzano lab will continue to oversee upkeep of gEAR, with a goal of making it even easier for HRP members to post their new data and for others in the community to analyze those data. The Edge lab will take the lead on the development of organoids as a screening platform for the future. The Heller, Hertzano, Raible, and Stone labs will validate markers by in situ hybridization across species, and all working group members will help direct the analysis.