1) Studies aimed at understanding the molecular mechanisms underlying the protective effects of HSPs Our studies indicate that a mild heat stress induces a protective state in utricles. We are investigating the roles of two specific HSPs (HSP70 and HSP32) as mediators of this protective effect. We find that each of these molecules inhibits ototoxic hair cell death. In addition, both of these molecules inhibit activation of pro-apoptotic c-Jun N-terminal kinase (JNK) in hair cells treated with aminoglycosides. We are currently examining which cell types in the inner ear respond to stress by upregulating HSP70 and HSP32. 2) Studies aimed at translating our findings into clinical therapies to prevent hearing loss caused by exposure to ototoxic drugs We have recently shown that a pharmacological HSP inducer called celastrol inhibits aminoglycoside-induced hair cell death and hearing loss in mice. We also showed that the mechanism underlying celastrols protective effect is via induction of HSP32. We are currently examining additional methods of inducing HSPs in the inner ear with the goal of developing a co-therapy that will protect the hearing of human patients receiving ototoxic drugs. I arrived at NIH as a Tenure-track Investigator in January 2011. I have spent a significant portion of 2011 staffing the laboratory and ordering equipment.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
National Institute on Deafness and Other Communication Disorders
Zip Code
Baker, Tiffany G; Roy, Soumen; Brandon, Carlene S et al. (2015) Heat shock protein-mediated protection against Cisplatin-induced hair cell death. J Assoc Res Otolaryngol 16:67-80
Chien, Wade W; Isgrig, Kevin; Roy, Soumen et al. (2015) Gene therapy restores hair cell stereocilia morphology in inner ears of deaf whirler mice. Mol Ther :
Drummond, Meghan C; Barzik, Melanie; Bird, Jonathan E et al. (2015) Live-cell imaging of actin dynamics reveals mechanisms of stereocilia length regulation in the inner ear. Nat Commun 6:6873
Wang, Tian; Chai, Renjie; Kim, Grace S et al. (2015) Lgr5+ cells regenerate hair cells via proliferation and direct transdifferentiation in damaged neonatal mouse utricle. Nat Commun 6:6613
Cunningham, Lisa L; Tucci, Debara L (2015) Restoring synaptic connections in the inner ear after noise damage. N Engl J Med 372:181-2
Chien, Wade W; McDougald, Devin S; Roy, Soumen et al. (2015) Cochlear gene transfer mediated by adeno-associated virus: Comparison of two surgical approaches. Laryngoscope :
Chien, Wade W; Monzack, Elyssa L; McDougald, Devin S et al. (2014) Gene Therapy for Sensorineural Hearing Loss. Ear Hear :
May, Lindsey A; Kramarenko, Inga I; Brandon, Carlene S et al. (2013) Inner ear supporting cells protect hair cells by secreting HSP70. J Clin Invest 123:3577-87
Roy, Soumen; Ryals, Matthew M; Van den Bruele, Astrid Botty et al. (2013) Sound preconditioning therapy inhibits ototoxic hearing loss in mice. J Clin Invest 123:4945-9
Brandon, Carlene S; Voelkel-Johnson, Christina; May, Lindsey A et al. (2012) Dissection of adult mouse utricle and adenovirus-mediated supporting-cell infection. J Vis Exp :

Showing the most recent 10 out of 11 publications