Highlights

Dr. Nicolson has received an R01 grant from NIH for her project “Diversification of the mechanotransduction complex in vestibular hair cells.”

Bouts of debilitating vertigo or dizziness rank amongst the most common reasons that patients seek medical care, especially among elderly patients. In part, these episodes of vertigo or dizziness are due to functional defects in vestibular hair cells. Dr. Nicolson and Dr. Cheng intend to leverage the advantages of both zebrafish and mice models of vestibular hair cell dysfunction along with comparative studies of human vestibular hair cells to gain a better understanding of the molecular components required for sensory function of vestibular hair cells.

The Grillet lab has been awarded an R01 grant from NIH entitled “Molecular Genetics of Human Age-Related Hearing Loss.”

The gradual loss of hearing is a common manifestation of aging, ultimately affecting communication and leading to social exclusion and cognitive decline. The genetics of age-related hearing loss is multifactorial, with more than 50 genetic variations being associated with this impairment in humans. To dissect this complex genetic situation, this project aims at replicating one of these human genetic variants in a mouse model. With this animal model, the Grillet lab will be able to investigate its impact on the inner ear function, determine if it increases sensitivity to noise damage, and finally test for relationships with other genes involved in age-related hearing loss. Overall, this project will advance our understanding of the molecular mechanisms underlying age-related hearing loss and how it can be delayed or prevented. 

Dr. Stankovic and Dr. Lei Xu of Massachusetts General Hospital are principal investigators on a newly awarded R01 grant from NIH entitled “Targeting HMGB1 to improve hearing andenhance therapy for vestibular schwannomas.”

Vestibular schwannomas (VSs) are intracranial tumors that cause progressive hearing loss and negatively impact quality of life. Identifying well-tolerated drugs to halt VS growth and ameliorate VS-associated hearing loss is a major unmet medical need. This project aims to provide insight into i) the role and mechanisms of HMGB1 in driving neuroinflammation in VS, ii) the treatment potential and the hearing response following HMGB1 blockade, and iii) the design of a future clinical trial for VS using a novel combination strategy of HMGB1 and EGFR blockade to concurrently control tumor growth and prevent VS-induced hearing loss.

Dr. Cheng has been awarded an K24 grant from NIH for his project “Mentoring Patient Oriented Research in sensory disorders.” 

This career development award is designed to investigate tropism of viral vectors for human inner ear tissues. The successful completion of this work can better inform methods to deliver therapeutics to improve hearing loss and balance functions in humans. Importantly, this award also allows protected time for mentoring physician-scienitst trainees and faculty.

Dr. George has been awarded an R21 grant from NIH for her project “Investigating the role of lipid membrane in the cochlear hair cell mechanotransduction.” 

Although there is a large body of work regarding lipid membrane modulation of mechanosensitive ion channels, there is a limited but growing body of data on lipid modulation of cochlear hair cell mechanotransduction.  In this project, Dr. George is combining electrophysiology with live-cell fluorescence lifetime imaging (FLIM) of new membrane sensors to examine the membrane viscosity and membrane order with improved spatio-temporal resolution for the first time in mammalian cochlea. She is assessing local and temporal changes in the stereocilia membrane viscosity with voltage, calcium, and membrane components like cholesterol and PIP2 and correlate these effects to changes in cochlear hair cell channel resting probability. These studies will enhance our basic understanding of the importance of lipid membrane in hair cell mechanotransduction. Understanding the crucial components in the mechanical underpinnings of the stereocilia is both biophysically and biologically relevant.

Dr. Ricci has received an S10 grant from NIH for his project “Abberior Infinity Line Upright 3D STED/Confocal Microscope.”

This quarter the Ricci Lab successfully competed for an equipment grant from NIH. This $1.76M grant will purchase a new super-resolution STED microscope. This microscope will allow us to resolve individual molecules down to 20 nm! This unprecedented resolution will allow the unraveling of the molecular interactions such as occurs in the sensory hair bundle mechanotransduction complex or at hair cell spiral ganglia synapses. This technology can be used in live in vivo and in vitro work and on histological tissue. As part of the departmental core facility, this equipment will be available to all scientists and serve as a technological bridge between our diverse research interests.

Dr. McGrath has received an F32 grant from NIH for his project “Investigating the role of mechanotransduction machinery and the rootlet in modulating stereocilia motion.”

Auditory hair cells have bundles of protrusions on their surface held together by proteinaceous links. Sound-induced vibrations deflect the bundles, transferring force through the links to open nearby ion channels. The electrical currents generated by these channels provide our sensation of sound. Compared to other hair cell types, the protrusions of mammalian auditory bundles are weakly coupled, yet we know little about how this contributes to hearing. Dr. McGrath is set out to characterize the mechanical underpinnings of the links holding the bundles together. By stimulating a sub-region of the bundle, his team will use the endogenous links to move the remaining protrusions and can monitor bundle connectivity by measuring their relative motions. This approach will be used while disrupting the links and pharmacologically blocking the channels to reveal their contributions to bundle mechanics. They will determine how the distinctive coupling of auditory hair cell bundle protrusions influences our ability to hear.

Dr. Ahmad has received a McCormick and Gabilan Faculty Award for her project “Radiographic Changes in the Auditory Pathway to Predict Outcomes of Children with Hearing Loss.”

Dr. Ahmad is studying sensorineural hearing loss (SNHL) in children.  SNHL is strongly associated with developmental delay thus early detection and intervention is critical. Information regarding underlying brain microstructure could offer insights into neural development in deaf children and potentially guide therapies that optimize language development. Dr. Ahmad is investigating MRI-based microstructural changes along the auditory pathway in pediatric patients with SNHL. Her project focuses on interrogating the auditory pathway using diffusion tensor imaging (DTI), a type of MRI. Diffusion MRI is used to identify microstructural changes in the brain, and can serve as an important tool to gain insight into neural development and to potentially prognosticate speech and language outcomes in children with SNHL. Dr. Ahmad’s work is the first to assess microstructural changes in brainstem auditory pathway regions among children with SNHL. Currently her study is evaluating the hearing outcomes of these patients with hearing aids and cochlear implants and are correlating this to the microstructural metrics found using DTI in SNHL.

Drs Capasso and Valdez have received a grant from the Stanford Woods Institute for the Environment for their project “Albert Einstein Hospital Upluxo Program: Disrupting Hospitals Fabric Reutilization.”

In Brazil, most hospital generated textiles are incinerated or sent to landfill. Although there are examples of textile waste recycling and occasional upcycling, examples in the healthcare industry are very scarce, and poorly structured. Drs Capasso and Valdez will lead the efforts at Stanford and will partner with the Hospital Albert Einstein team to change hospital textile waste management via a new software paradigm: engineering a traceable, data-driven system to identify and predict waste patterns and adequately and efficiently redirect hospitals' textile waste to upcycling in a decentralized network. A new interactive digital tool that leverages modeling software will allow users to visualize and map the value provided by upcycling ecosystem services, combining sustainable waste interventions and economic welfare for vulnerable communities.

Drs Santa Maria and Steenerson have received both grants for their project, “DizzyDx: A Dizzy Attack Event Monitor.”