(2hn) Translational Research for Auditory and Sensory Systems.

Research Interests: Sensorineural hearing loss (SNHL) is a significant sensory and neurodegenerative problem globally. There are many types of SNHL, including age-related hearing loss (ARHL, also known as presbycusis), noise-induced hearing loss (NIHL), drug-induced hearing loss (DIHL), and genetics. In addition to affecting communication abilities, SNHL is associated with other health and social implications such as cognitive decline, balance issues, increased dependence on others, decreased job performance, and several others etc. Advancement in technologies such as hearing aid helped individuals to a certain degree, most users are do not perceive the outcomes to be consequential and less motivated to use hearing aids consistently. Hence, finding solutions – technological/pharmaceutical for SNHL will help individuals regain/prevent their hearing abilities and address associated health implications, thus enhancing their overall well-being. Further, different types of SNHL shared common etiologies such as increased inflammation, mitochondrial dysfunction, and oxidative stress etc., however, time scales of exposure are very different for various types of hearing loss. Hence, investigating intervention solution for a single SNHL will have a broader applicability for others.

While my PhD in auditory neuroscience enabled intimate understanding of different facets of auditory and sensory problems, my engineering background empowers me to bring unique prospective, helping in designing smarter solutions for SNHL. More specifically, my research plan will revolve around three major themes:

Drug Discovery: Presently, there is no FDA-approved drug for any of the SNHL, ARHL, noise exposure, or ototoxicity (cis-platin, antibiotics). Researchers have made significant progress regarding cellular and molecular mechanisms involved in different types of SNHL. To illustrate, various key underlying mechanisms of ARHL are reactive oxygen species (ROS), chronic inflammation, DNA mutation, mitochondrial damage etc. Pre-clinical studies are conducted utilizing these pathways with antioxidants, hormones, anti-inflammatories, and other compounds. Still, none of them has successfully obtained the FDA approval. In this context, my research plan aims to complete the preclinical studies leading to clinical trials for a particular type of hearing loss. It includes testing novel compounds in rodent animal models for hearing protection, either a single compound or a mixture of compounds.

Presently, I have a NIH-NIDCD R21, an early career grant from American Hearing Research Foundation, and a seed grant from USF to develop therapies for ARHL, with a particular focus on nutraceuticals. The vision for these grants is to lay a strong foundation by generation ground-breaking data which aids in securing future multiyear NIH and other federal grants.

Developing New Diagnostic Tools and Identifying Early Biomarkers: Identifying early biomarkers and developing new diagnostic tools are critical for early detection, therapeutic development, timely intervention, and improved treatment outcomes. In my lab, focus will be on biomarker discovery and the development of new diagnostic tools for the early detection of auditory pathologies. The human inner ear is a fascinating spiral structure comprised of three parts compartments, where the middle section (scala media) has high potassium and low sodium concentrations compared to its surroundings (scala tympani and scala vestibuli). This ionic difference leads to an electrical potential of ~100 mV in the scala media. The ionic homeostasis and voltage difference play a critical role in normal hearing function, and their imbalance is involved in various auditory pathologies such as ARHL and NIHL. Current laboratory techniques that are used over animal models for ionic concentrations and inner ear battery measurements are invasive and terminal. These methods cannot be used in humans. So, there is a compelling need to develop non-invasive clinically relevant imaging/measurement techniques to assess various biological processes in the auditory system, focusing on the peripheral system – the inner ear. My lab will focus on developing such tools using advanced imaging techniques like MRI, Molecular Imaging techniques, and others. I have another NIH-NIDCD R21 grant (co-investigator) and a foundation grant (PI) from the American Otological Society to explore the possibility of utilizing nuclear and molecular imaging techniques for measuring inner ear functions non-invasively – ionic concentrations and the endocochlear potentials.

Developing Technological Engineering Interventions: The third theme of our lab will focus on developing next-generation technology for biomedical testing, drug delivery, and prosthetic devices. The existing prosthetic stimulation devices, including cochlear implants, are limited by low spatial resolution due to the non-specific stimulation characteristics of electrical stimulation, i.e., the spread of electric fields in space generated due to diffuse electric currents, thus, compromising the hearing quality. In my PhD work was focused on establishing the protocols for achieving the specific localized stimulation in auditory and neural systems in-vitro using nanoparticles and visible light. Though some exciting progress has been made, still, there is a long way to go to realize the application of these emerging technologies (light-based neural stimulation devices). Most studies are in-vitro; robust in-vivo animal models are yet to be established. In my new lab, we will implement these emerging optical techniques in-vivo and develop implantable devices with a particular focus on cochlear implants.

Under this theme, I will also focus on other engineering solutions, such as developing advanced inner ear drug delivery systems. As mentioned, there is no biomedical therapeutics for hearing disorders or deafness. Many potential therapeutic compounds have systemic side effects or are toxic and cannot be delivered orally or systemically. However, with the rapid development of microengineering and microfluidic technologies, there is a solid opportunity to develop local drug delivery platforms for inner ear drug delivery.

Current Research Grants: NIH/NIDCD – R21 DC021546-01 (Role: MPI; 2023-2025), NIH/NIDCD – R21 DC020091-01A1 (Role: Co-Investigator; 2022-2024), American Hearing Research Foundation – Richard G. Muench Chairman Grant GRT 13053 (Role: PI; 2023), American Otological Society – The Research Grant (Role: PI; 2023-2024), New Research Grant – University of South Florida (Role: PI; 2023-2024).

Research Experiences: Presently, I work as Research Assistant Professor at Medical Eng. Dept., University of South Florida, Tampa, FL. My work primarily revolves around neuroscience, audiology, and biomedical engineering research. Over the years, I have been engaged in numerous multidisciplinary research projects, broadening my horizons across various research domains, including grant writing. Some of the successful projects such as Nano-optical Neural Stimulations (PhD Dissertation), Anti-inflammatory therapies for the aging auditory system (Postdoctoral Work), Nutraceuticals for hearing loss treatment, Micropump development for inner ear drug delivery, and Non-invasive Imaging of Inner Ear.

Along with research, I have mentored numerous students throughout my academic career at all levels, high school, undergraduate, and graduate students, including REU (Research Experiences for Undergraduates) students – a NSF-funded program for Undergraduates. Many mentees have gone to top universities nationwide for PhDs and/or Medical studies, as well as industry, to further their careers. I help students with assistance, such as application preparation, referral letters, sound career advice etc. I always design research projects as per students’ aspirations and career goals.

Teaching Experiences: I had opportunities to teach students throughout my career – I had a teaching experience after my BS (for 1 year) and MS studies (for 1.5 years) and during my graduate studies and postdoctoral experiences (details included in the CV). For example, for the past 6 years, I have been giving lectures in Prof. Robert Frisina’s course – Basics of Biomedical Engineering (BME 4100/5105), where I deliver lectures every semester on nanomedicine, molecular imaging, and neural stimulation. During my Ph.D., I worked as a Teaching Assistant for various Chemical Engineering courses. I have always received positive feedback and reviews about my teaching for lectures and regular office hour sessions.

Teaching Interests: Given my teaching experience and expertise in different fields (Chemical Engineering, Neuroscience, Auditory Physiology, Nanotechnology, Material Science), I can indeed teach courses in many disciplines. My engineering and science training in chemical engineering has made me confident in delivering most core chemical engineering courses such as Transport Processes, Engineering Mathematics, Chemical Reaction Engineering, Fluid Mechanics, Separation Processes, and Process Control. Further, with me over a decade of research experience (PhD, Postdoctoral and beyond) in interdisciplinary areas (central focus – biomedical engineering and hearing/deafness), I am keen on designing and teaching other interdisciplinary courses such as Engineering Physiology, Bioelectricity, Auditory Anatomical Physiology, and Intro to Biomedical Engineering, etc.

Selected Publications:

1. Bauer, M., *Bazard, P., Acosta A. A., Bangalore, N., Thivierge, M., Chellani, M.; Zhu, X., Ding, B., Walton, J.P., *Frisina, R. D., L-Ergothioneine Slows the Progression of Age-related Hearing Loss in CBA/CaJ Mice. In-Press. *Corresponding Authors
2. Bazard, P., Frisina, R. D., Acosta, A., Dasgupta, S., Zhu, X., Ding, B., Role of Various Ion Channels in Age-related Hearing Loss, International Journal of Molecular Sciences, 21(11), 6158 – 2021 – Top downloaded article in 2021
3. Bazard, P, Ding, B., Chittam, H.K., Zhu, X., Parks, T. A., Taylor-Clark, T. E., Bhethanabotla, V.R., Frisina, R.D., Walton, J.P, Aldosterone up-regulates Voltage-gated Potassium Currents and NKCC1 Protein Membrane Fractions, Scientific Reports, 10 (1), 15604 – 2020
4. Damnjanovic, R., Bazard, P., Frisina, R.D., Bhethanabotla, V.R., Hybrid Electro-Plasmonic Neural Stimulation with Visible-Light-Sensitive Gold Nanoparticles, ACS Nano, 14 (9), 10917-10928 – 2020 – Featured Article
5. Bazard, P., Frisina, R.D., Walton, J.P, Bhethanabotla, V.R. Nanoparticle-based Plasmonic Transduction for Modulation of Electrically Excitable Cells, Scientific Reports, 7(1), 7803 – 2017