Room 403E Walton Research Building

Phone: 843-792-8324

Education:

• B.A., Audiology, University of Tennessee, 1990
• M.A., Audiology, University of Tennessee, 1991
• Clinical Fellowship in Audiology, Indiana University Medical Center 1992-1993
• Ph.D., Neuroscience, University of Virginia 1999
• Post-doctoral Fellowship in Auditory Neuroscience, University of Washington, 1999-2003

Research Interests:

This is a neuroscience laboratory focused on the mechanosensory hair cells that are the sensory cells of the inner ear.  These cells are responsible for transducing sound energy into neural signals.  Hair cells are susceptible to death from noise trauma, aging, genetic disorders, and certain therapeutic drugs.  The two primary classes of ototoxic drugs are the aminoglycoside antibiotics and the anticancer drug cisplatin.  Because mammalian hair cells are not regenerated, the hearing loss that results from hair cell death is permanent.  Hair cell death is often apoptotic, meaning the cell is activating an intrinsic program of cellular suicide.  The goal of work in our laboratory is to examine the molecules and signal transduction pathways that are involved in regulation of hair cell survival and death.  Two model systems are currently in use in the laboratory:  mammalian hair cells in culture allow us to closely examine cellular responses to stress, and the HEI-OC1 cell line allows us to perform multiple biochemical assays.  We have found that hair cell death caused by exposure to the ototoxic drug neomycin requires activation of both caspase-9 and Jun kinase (JNK), and it is inhibited by overexpression of Bcl-2.  Recently we have shown that induction of heat shock proteins (HSPs) can inhibit both aminoglycoside- and cisplatin-induced hair cell death.   HSPs are evolutionarily-conserved molecules that are activated in response to cellular stress and can inhibit apoptosis by interfering with pro-apoptotic proteins.  We are currently examining the molecular mechanism(s) underlying the protective effect of HSP induction in hair cells. 

Hair cell

Click here to see a movie of the mouse utricle dissection

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Publications:

Miyamoto, RT; Osberger, MJ; Cunningham, LL; Kirk, KI; Myres, W; Robbins, A; Kessler, K (1994): Single-Channel to Multi-Channel Conversions in Pediatric Cochlear Implant Recipients American Journal of Otology 15(1):40-45.

Rajendran, RR; VanNiel, EE; Stenkamp, DL; Cunningham, LL; Raymond, PA; Gonzalez-Fernandez, F (1996): Zebrafish Interphotoreceptor Retinoid-Binding Protein: Differential Circadian Expression Among Cone Subtypes Journal of Experimental Biology 199:2775-2787.

Stenkamp, DL; Cunningham, LL; Raymond, PA; Gonzalez-Fernandez, F. (1998): Novel Expression Patterns of Interphotoreceptor Retinoid-Binding Protein (IRBP) in the Developing and Adult Zebrafish Retina and RPE Molecular Vision 4:26-39.

Cunningham, LL; Yang, L; Gonzalez-Fernandez, F (1999): Interphotoreceptor Retinoid-Binding Protein (IRBP) is Rapidly Cleared from the Xenopus Interphotoreceptor Matrix Experimental Eye Research 68:399-410.

Cunningham, LL and Gonzalez-Fernandez, F. (2000): Coordination between Production and Turnover of Interphotoreceptor Retinoid-Binding Protein (IRBP) in Zebrafish Invest Ophthalmol Vis Sci. Oct;41(11):3590-9.

Cunningham, LL, Cheng, AG and Rubel, EW (2002): Caspase Activation in Hair Cells of the Mouse Utricle Exposed to Neomycin J. Neuroscience 22(19):8532-8540.

Cheng, AG; Cunningham, LL and Rubel, EW (2003): Hair Cell Death in the Avian Basilar Papilla: Characterization of the in vitro Model and Caspase Activation J. Assoc Res Otolaryngol 4(1):91-105.

Harris, JA; Cheng, AG; Cunningham, LL; Raible, DW; Rubel EW (2003): Neomycin-induced Hair Cell Death in the Lateral Line of Zebrafish (Danio rerio): a Model System to Study Hair Cell Survival. J. Assoc Res Otolaryngol 4(2):219.

Cunningham, LL and Gonzalez-Fernandez, F (2003). Internalization of Interphotoreceptor Retinoid-Binding Protein (IRBP) by the Xenopus Retinal Pigment Epithelium. J. Comp. Neurol. 466:331.

Murakami, SL; Cunningham, LL; Werner, LA; Bauer, E; Pujol, R; Raible, DW; Rubel, EW (2003) Developmental Differences in Susceptibility to Neomycin-Induced Hair Cell Death in the Lateral Line Neuromasts of Zebrafish (Danio rerio). Hear Res. Dec;186(1-2):47-56.

Cunningham, LL; Matsui, JI; Warchol, ME; Rubel, EW (2004) Overexpression of Bcl-2 prevents neomycin-induced hair cell death and caspase-9 activation in the adult mouse utricle in vitro. J. Neurobiology 60(1):89-100.

Heydt, JL; Cunningham, LL; Rubel, EW; Coltrera, MD (2004). Round window gentamicin application: an inner ear hair cell damage protocol for the mouse. Hear. Res. 192:65-74.

Cheng, AG; Cunningham, LL and Rubel EW (2005):  Mechanisms of hair cell death and protection Curr Opin Otolaryngol Head Neck Surg 13:343-348.

Cunningham, LL (2006):  The adult mouse utricle as an in vitro preparation for studies of ototoxic drug-induced sensory hair cell death.  Brain Research May 26;1091(1):277-81.
 
Cunningham, LL and Brandon, CS (2006):  Heat shock inhibits both aminoglycoside- and cisplatin-induced sensory hair cell death.  J. Assoc Res Otolaryngol. 7(3):299.

Sugahara, K; Rubel, EW; Cunningham, LL (2006): JNK signaling in neomycin-induced vestibular hair cell death. Hear. Res. 221(1-2):128-135.

Chiu, LL; Cunningham, LL; Raible, DW; Rubel, EW; Ou, HC (in press): Using the zebrafish lateral line to screen for ototoxicity.  In press J. Assoc Res Otolaryngol.

Taleb, M; Brandon, CS; Lee, F-S; Lomax, MI; Dillmann, WH; Cunningham, LL (in press): Hsp70 inhibits aminoglycoside-induced hair cell death and is necessary for the protective effect of heat shock.  In press J. Assoc Res Otolaryngol.

List of publications via PUBMED (NIH National Library of Medicine)