Lisa L. Cunningham, Ph.D.
Section on Sensory Cell Biology
Porter Neuroscience Research Center, Room 1D971
35 Convent Drive
Bethesda, MD 20892
Our research is focused on the mechanosensory hair cells that are the receptor cells of hearing and balance. Specifically, we are interested in the molecular signals that regulate the survival, homeostasis, and death of these cells. Mammalian hair cells are terminally differentiated and are not regenerated when they are lost. Therefore, human hair cells must survive and function for up to a century (or longer) in order to transduce sound and head movement into the neural signals of hearing and balance throughout a normal lifespan. During this lengthy period of time, the hair cell may encounter multiple potentially-toxic stimuli, including exposure to excessive sound and/or exposure to therapeutic drugs with ototoxic side effects. Hair cells must be able to respond rapidly and effectively to these and other potentially-cytotoxic stimuli if they are to survive and continue to function.
We are examining the signals that mediate the survival and death of hair cells under stress. We are currently studying the role of stress-induced proteins called heat shock proteins (HSPs) in protecting against hair cell death. Our studies use an in vitro preparation of the adult mouse utricle (a balance organ in the inner ear), which is the best-characterized model system for in vitro studies of mature mammalian hair cells. Using this preparation, we have shown that HSPs inhibit hair cell death caused by both major classes of ototoxic drugs, namely the aminoglycoside antibiotics and the antineoplastic agent cisplatin. In addition, we have shown that mice that constitutively express HSP70 are resistant to hearing loss and cochlear hair cell death caused by systemic aminoglycoside exposure. Our studies indicate that HSP induction is a critical stress response in the inner ear that can promote survival of hair cells exposed to major stressors.
Currently our studies are broadly divided into two groups: 1) those aimed at understanding the molecular mechanisms underlying the protective effects of HSPs and 2) those aimed at translating our findings into clinical therapies to prevent hearing loss caused by exposure to ototoxic drugs.
Dr. Cunningham received a B.A. and M.A. in Audiology from the University of Tennessee, Knoxville. She completed a Clinical Fellowship in Audiology at Indiana University Medical Center in Indianapolis. She received a Ph.D. in Neuroscience from the University of Virginia and then completed a post-doctoral fellowship in Auditory Neuroscience at the University of Washington in Seattle. Dr. Cunningham started her own lab at the Medical University of South Carolina in 2004 where she conducted the initial studies on heat shock protein (HSP)-mediated protection against ototoxic drug-induced hearing loss and hair cell death. This work was funded by a Research Project Grant (R01) from the NIDCD. Dr. Cunningham moved to the NIDCD's Section on Sensory Cell Biology in 2011.
Francis SP, Kramarenko II, Brandon CS, Lee FS, Baker TG, Cunningham LL. Celastrol inhibits aminoglycoside-induced ototoxicity via heat shock protein 32. Cell Death Dis. 2011;2:e195.
Taleb M, Brandon CS, Lee FS, Harris KC, Dillmann WH, Cunningham LL. Hsp70 inhibits aminoglycoside-induced hearing loss and cochlear hair cell death. Cell Stress Chaperones. 2009;14(4):427-37.
Cunningham LL, Brandon CS. Heat shock inhibits both aminoglycoside- and cisplatin-induced sensory hair cell death. J Assoc Res Otolaryngol. 2006;7(3):299-307.
Monzack EL, May LA, Roy S, Gale JE, Cunningham LL. Live imaging the phagocytic activity of inner ear supporting cells in response to hair cell death. Cell Death Differ. 2015;22(12):1995-2005.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
This page was last updated on July 31st, 2017