Current Research
Our ability to hear shapes our daily experiences, connecting us to the world and enriching our sensory perception. The profound impact of hearing loss extends beyond mere auditory impairment, affecting cognitive health, self-identity, and confidence to thrive in one's environment. Recent research efforts have intensified, focusing on preventive and restorative treatment methods to address this pervasive public health issue focusing specifically on the hair cells of the cochlea. The imminent revolution in hearing loss treatment holds great promise, providing a long-awaited disruption to the therapeutic landscape. However, alongside drug formulation, is the development of an appropriate drug delivery system. Determining the most effective and safe means of transporting medication while prioritizing patient comfort is a significant challenge. Unlike conventional delivery methods for flu shots or cough syrup, inner ear drug delivery demands a nuanced approach.
The primary challenge for systemic delivery to the inner ear is achieving a therapeutic dose across the blood-labyrinth barrier without causing systemic side effects. Local administration routes, such as intratympanic and intracochlear methods, present alternatives that bypass blood-labyrinth barrier issues encountered with systemic administration. However, these local methods come with drawbacks, including temporary or permanent hearing loss or low efficiency.
Our lab addresses the significant challenges inherent in developing effective inner ear substance delivery systems. One key hurdle involves not knowing the exact drug formulation for which the delivery system is being designed, affecting drug bioavailability and biodistribution. Another obstacle lies in translating promising findings from preclinical studies, conducted on animal models, into applicable solutions for human patients. Synergistic collaborations between hearing healthcare professionals and scientists, along with technological innovations such as 3D imaging and nanotechnology, would pave the way for transformative advancements in inner ear drug delivery systems.
If you are interested in joining our research team, please contact me at amoatti@pitt.edu.
Current research projects:
- Developing ex-vivo and in-vivo models of drug delivery in large animals such as pigs similar to humans.
- Developing extracellular vesicles as efficacious and safe carriers to deliver therapy-related substances to the inner ear.
- Identifying novel sensory receptors and channels of round window membrane that sense chemicals, investigating how receptors and channels regulate drug passage to the inner ear, and harnessing receptors and channels to improve inner ear drug delivery.
- In vivo and ex-vivo 3D high-resolution imaging for inner ear visualization, metabolomics, inflammation, and drug biodistribution.
- Evaluate promising regeneration therapy effects delivered safely in a clinically relevant animal model like pigs.
- Nanomaterials and smart materials to improve drug delivery to the inner ear.
Selected Recent Publications
Surgical Procedure of Intratympanic Injection and Inner Ear Pharmacokinetics Simulation in Domestic Pigs.
Front Pharmacol 2024
Moatti A, Connard S, Fitzpatrick D, Hutson K, Zdanski C, Ligler F, Greenbaum A.
Assessment of drug permeability through an ex vivo porcine round window membrane model.
iScience 2023
Moatti A, Silkstone D, Martin T, Abbey K, Hutson KA, Fitzpatrick DC, Zdanski CJ, Cheng AG, Ligler FS, Greenbaum A
Tissue clearing and three-dimensional imaging of the whole cochlea and vestibular system from multiple large-animal models
STAR Protoc 2023
Moatti A, Cai Y, Li C, Popowski KD, Cheng K, Ligler FS, Greenbaum A
Ontogeny of cellular organization and LGR5 expression in porcine cochlea revealed using tissue clearing and 3D imaging
iScience 2022
Moatti A, Li C, Sivadanam S, Cai Y, Ranta J, Piedrahita JA, Cheng AG, Ligler FS, Greenbaum A.
Three-dimensional imaging of intact porcine cochlea using tissue clearing and custom-built light-sheet microscopy. Biomed Opt Express
Biomed Opt Express 2020
Moatti A, Cai Y, Li C, Sattler T, Edwards L, Piedrahita J, Ligler FS, Greenbaum A
Inhalable dry powder mRNA vaccines based on extracellular vesicles
Matter 2022
Popowski KD, Moatti A, Scull G, Silkstone D, Lutz H, López de Juan Abad B, George A, Belcher E, Zhu D, Mei X, Cheng X, Cislo M, Ghodsi A, Cai Y, Huang K, Li J, Brown AC, Greenbaum A, Dinh PC, Cheng K
Enhancement of bone regeneration through the converse piezoelectric effect, a novel approach for applying mechanical stimulation
Bioelectricity 2021
Carter A, Popowski K, Cheng K, Greenbaum A, Ligler FS, Moatti A
A gene edited pig model for studying LGR5+ stem cells: implications for future applications in tissue regeneration and biomedical research
Front. Genome Ed 2024
Hill A, Murphy Y, Polkoff K, Edwards L, Walker D, Moatti A, Greenbaum A, Piedrahita J
Erratum: Deep learning-based autofocus method enhances image quality in light-sheet fluorescence microscopy: publisher's note
Biomed Opt Express 2021
Li C, Moatti A, Zhang X, Ghashghaei HT, Greenbaum A
Spiner, Deep Learning-Based Automated Detection of Spiral Ganglion Neurons in Intact Cochleae
https://dx.doi.org/10.2139/ssrn.4820264
Cai Y, Leitz-Najarian G, Hutson K, Moatti A, Li C, Fitzpatrick D, Greenbaum A