Member: Hearing Restoration Project
Current Institution: Creighton University
Education: Tsinghua University, B.Sc. and M.Sc.; University of Southern California, Ph.D. and postdoctorate work
What is your area of focus?
We are interested in the role of epigenetic repression (i.e., chromatin architecture and histone modifications to block gene expression) in the silencing of sensory hair cell programming in the supporting cells of the mammalian cochlea. We hypothesize that in mammals, the epigenetic silencing state of hair cell genes in supporting cells hampers reactivation of those genes and hence blocks the conversion of supporting cells to hair cells, one major hair cell regeneration mechanism found in non-mammalian animals. Investigation of the epigenetic regulatory mechanisms not only helps us understand the failure of sensory hair cell regeneration in humans, but also provides potential targets for us to manipulate the epigenetic status of genes to stimulate gene expression for hair cell regeneration toward hearing restoration.
Why did you decide to get into scientific research?
Chinese Taoism teaches that every movement or change in the universe is dictated by certain rules (“道”) and that people become powerful if they understand those rules. When I was a kid, I was fascinated by Taoist stories, and I started to pay close attention to natural phenomena to understand the rules behind them. Expectedly and unexpectedly, I found myself interested in science and became a scientist instead of a Taoist.
Why hearing research?
The first time I saw the structure of the human cochlea, I was immediately drawn by the delicate structure and the beauty of sensory hair cells. On top of this, I had the good fortune to work with the late Neil Segil, Ph.D., who was a member of HHF’s Hearing Restoration Project. Dr. Segil welcomed me as a Ph.D. student and encouraged me to study hair cell death induced by aminoglycoside antibiotics. From these ototoxicity studies conducted in the supportive environment of the Segil lab, I developed a fondness for the science of the inner ear.
What is the most exciting part of your research?
Compared with other tissues and organs, the cochlea presents unique challenges in order to be studied. This tiny organ is buried in a bony structure and contains a limited number of specialized cells. Implementing new techniques and designing novel experimental approaches to overcome these challenges is an ongoing journey in hearing research and an essential part of the job, without which many of our biggest questions would be difficult or impossible to address. The most exciting part of our work is to see results generated successfully with these new techniques and approaches, regardless of whether they support or contradict our hypotheses.
Describe a typical day.
After dropping my daughter off at school, I begin my workday catching up on email correspondence. Then I walk into the lab to greet my lab members, and if I don’t have a lecture to give, I’ll discuss experiments with them. Next, I spend an hour or two putting together lecture materials, analyzing new datasets, or preparing presentation slides. Lunch is usually followed by student presentations, journal club discussions, seminars featuring an invited speaker, or department meetings. I spend most of my time in the afternoon in various meetings and discussions with students, lab members, colleagues, and collaborators. After finishing up any paperwork, reading and sending a few more emails, I say goodbye to the lab and head home. When it gets dark, I spend my evenings playing basketball or jogging for a little while, and then enjoy some reading or writing before bed.
Tell us something you enjoy doing outside the lab.
I like fishing. I used to go deep sea fishing or surf fishing once a week when I lived in Los Angeles, and now I am exploring the fun in lake fishing and river fishing in the Midwest. Staring at the float or pole tip quickly isolates me from the surrounding environment so that I can think about something without interruption from the world outside. Of course, the bites from any fish always pull me back to the real world.
How has the collaborative effort helped your research?
The question as to why the mammalian cochlea lost the capacity to regenerate sensory hair cells while robust hair cell regeneration happens in non-mammalian animals requires the investigation of the auditory organs of multiple species. The collaborative effort from multiple groups working with a variety of species makes it possible to address this intriguing and important question. Everyone has their own unique expertise and can provide critical feedback from angles I would never have considered myself. With so many branches of auditory research to keep in mind, even a brief conversation can provide very important reminders and key pieces to a puzzle.
What do you hope for the HRP over the next few years?
The HRP brings some of the greatest minds in auditory science together, supporting many diverse projects by encouraging collaboration and cooperation. This unique platform has greatly accelerated hearing research and played a significant role in advancing our knowledge of the inner ear. Over the next few years, I would like to see more resources allocated to projects geared toward the translational aspect of hearing research, with themes such as drug screening, gene delivery, and expression manipulation for potential therapeutic treatments. Of course, we cannot make this happen without the continued support from HHF and its generous donors.
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.