Research Area Affiliations
Dr. Kantardzhieva began her work in auditory biology by generating and characterizing a transgenic mouse model for Isl1 to advance current knowledge of factors related to hearing loss and protection. The Isl1 transgenic mice showed significantly less threshold elevation and hair cell loss, associated normally with aging, compared to wild type controls. In addition, the Isl1 overexpression protected the ear from noise-induced hearing loss. This work led to a patent application.
In her next project, Dr. Kantardzhieva studied the protein composition of the synaptic ribbon and its closely associated pre-synaptic area, using affinity chromatography coupled to proteomics. Quantities of ribbon proteins were high enough to observe stochiometric relationships. Her findings led to a testable hypothesis that the ribbon proteins initiate vesicle fission to create vesicles near the synaptic ribbon from larger, membrane-enclosed endocytosed structures (cisterns). To test this hypothesis, she analyzed the distribution of vesicles and cisterns around ribbons from serial sections of inner hair cells. She then identified a “sphere of influence” of 350 nm around the ribbon, with fewer cisterns and many more synaptic vesicles.
Dr. Kantardzhieva’s current project focuses on her laboratory’s discovery that there is a brief period following noise exposure when the ear is capable of limiting the damage, and a transcription factor Plzf is necessary for this process. The inability of Plzf-mutant mice to induce rescue provides an opportunity to discover the underlying repair mechanisms, and provides an opportunity for therapy development.
Her goal is to develop practical applications dealing with protein/peptide targets.
MPP5 recruits MPP4 to the CRB1 complex in photoreceptors. Kantardzhieva, A.; Gosens, I.; Alexeeva, S.; Punte, I. M.; Versteeg, I.; Krieger, E.; Neefjes-Mol, C. A.; den Hollander, A. I.; Letteboer, S. J.; Klooster, J.; Cremers, F. P.; Roepman, R.; Wijnholds, J.: Invest Ophthalmol Vis Sci 2005, 46, 2192-201.
MPP3 is recruited to the MPP5 protein scaffold at the retinal outer limiting membrane. Kantardzhieva, A.; Alexeeva, S.; Versteeg, I.; Wijnholds, J.: FEBS J 2006, 273, 1152-65.
Loss-of-function mutations in the PRPS1 gene cause a type of nonsyndromic X-linked sensorineural deafness, DFN2. Liu, X.; Han, D.; Li, J.; Han, B.; Ouyang, X.; Cheng, J.; Li, X.; Jin, Z.; Wang, Y.; Bitner-Glindzicz, M.; Kong, X.; Xu, H.; Kantardzhieva, A.; Eavey, R. D.; Seidman, C. E.; Seidman, J. G.; Du, L. L.; Chen, Z. Y.; Dai, P.; Teng, M.; Yan, D.; Yuan, H.: Am J Hum Genet 2010, 86, 65-71.
Protein composition of immunoprecipitated synaptic ribbons. Kantardzhieva, A.; Peppi, M.; Lane, W. S.; Sewell, W. F.: J Proteome Res 2012, 11, 1163-74.
Quantitative analysis of ribbons, vesicles, and cisterns at the inner hair cell synapse: similarities and differences between fibers with low vs. high spontaneous rates. Kantardzhieva, A.; Liberman M.C., Sewell, W. F.: J Comp Neurol, 2013, doi: 10.1002/cne.23345
View a complete list of publications on pubmed.gov »