Spotlight
Winter 2024 Newsletter
The Stanford Initiative to Cure Hearing Loss (SICHL) is focused on developing new treatments and potential cures for hearing loss, which currently affects 1.5 billion people worldwide. Towards the goal of advancing our understanding of the biological mechanisms of hearing loss, the researchers at SICHL study all aspects of the auditory system, from the ear to the brain, in humans as well as in a variety of cellular and animal model systems.
Many exciting discoveries have recently emerged from research groups at SICHL that are helping to overcome long-standing challenges in treating hearing loss, using tools spanning molecular biology, genetics, stem cell and regenerative biology, electrophysiology, structural biology, and computational modeling.
A team lead by Dr. Alan Cheng performed single-cell RNA sequencing of living inner ear tissues from surgical patients and organ donors and used computational approaches to establish the first molecular atlas of the normal and diseased human inner ear sensory organs.
Remarkably, they discovered that human inner ear tissues with degenerating hair cells do show evidence of regenerative responses, although the process is incomplete. The next step is to determine how to sustain this regenerative process to repair the damaged cells in humans, which may be informed by recent work from the lab of Dr. Stefan Heller. They uncovered a new cell signaling mechanism directing hair cell regeneration in the chicken cochlea, an important model of hearing loss due to birds’ ability to spontaneously replace missing hair cells, that prompts cells to divide.
A primary challenge when diagnosing the unique cause of a patient’s hearing loss is that the cells within the cochlea are too small to be imaged with MRI, CT, or other clinical imaging methods. However, a team led by Dr. Konstantina Stankovic and Dr. Gary Tearney have utilized an imaging method called dynamic micro-optical coherence tomography to provide high-resolution images of inner ear cells and gain information about their health and metabolism. They are now working on implementing this technology into a tiny microendoscope to help identify which cochlear cells are healthy, unhealthy, or missing altogether and then direct the choice of the best therapy for a patient’s specific type of hearing loss.
Towards overcoming challenges for the delivery of therapies to the fragile inner ear, a recent study from the lab of Dr. Anthony Ricci showed that drugs can be selectively delivered to the inner ear’s perilymphatic space in a controlled manner that does not damage either hearing or vestibular function. Additionally, the lab of Dr. Tulio Valdez is developing “nanocarrier” molecules, which could deliver medications across the intact eardrum to the middle and inner ear. His lab is also using advanced imaging techniques to rapidly diagnose middle ear infection, a common cause of both temporary and permanent hearing loss.
About half of all hearing loss is caused by genetic mutations which, if well understood, could be candidates for gene therapy. A team led by Dr. Nicholas Grillet discovered that a gene called LOXHD1 causes a form of inherited hearing loss in humans. Their work, published in two articles in Nature Communications, revealed unprecedented details on the molecular causes of this genetic deafness and was featured on the journal’s front page.
Additionally, the lab of Dr. Teresa Nicholson has used zebrafish with a mutation in the gene vps4a, a model of deafness caused by corresponding human gene in patients. They recently demonstrated that the gene mutation impacts cell-cell communication in response to sensory cues from sound, which may help form the basis for new therapies for patients with VPS4A mutations and hearing loss.
SICHL is also contributing to the advancement of artificial intelligence and machine learning research, which could benefit people with hearing loss. Dr. Matthew Fitzgerald and Dr. Malcom Slaney compared the ability of automatic speech recognition (ASR) programs to detect speech in noisy environments compared to a human listener. Creating this benchmark can help to improve ASR programs which are widely used by people both with and without hearing loss. Dr. Dáibhid Ó Maoiléidigh's laboratory uses mathematical and computational approaches to study hearing and balance, including by modeling the structural and mechanical properties of the stereocilia of hair cells. Stereocilia are essential for the detection of sound and are one of the most common parts of hair cells to be damaged by noise, so understanding their normal machinery can inform strategies for repair.
The work of SICHL has recently been featured in multiple media sources including on CBS Mornings, “90 Seconds with Lisa Kim”, and the New York Times, which also highlight the journey of singer-songwriter Paul Simon with hearing loss and his support of the mission of SICHL. Paul lost hearing in his left ear while working on his most recent album, “Seven Psalms,” and recently performed a concert in New York City to help raise awareness of SICHL.