Proceedings of the National Academy of Sciences, 2014
Significance Hearing impairment is most frequently caused by the loss of sensory hair cells in th... more Significance Hearing impairment is most frequently caused by the loss of sensory hair cells in the cochlea. One potential means of alleviating hearing loss is to restore these cells, which do not naturally regenerate in mammals. The zebrafish lateral line serves as a useful model for studying hair-cell regeneration because in this system there exist progenitors, mantle cells, from which hair-cell precursors originate. We have produced zebrafish with fluorescently labeled mantle cells, isolated those cells by flow cytometry, and analyzed the transcripts that they express. We have also defined the temporal window during which mantle cells respond to hair-cell death. This approach has identified genes representing unexpected signaling pathways that may contribute to the development of treatments for hearing loss.
Proceedings of the National Academy of Sciences, 2007
Sudden cardiac death due to abnormal heart rhythm kills 400,000–460,000 Americans each year. To i... more Sudden cardiac death due to abnormal heart rhythm kills 400,000–460,000 Americans each year. To identify genes that regulate heart rhythm, we are developing a screen that uses mouse embryonic stem cells (mESCs) with gene disruptions that can be differentiated into cardiac cells for phenotyping. Here, we show that the heterozygous disruption of the Akap10 (D-AKAP2) gene that disrupts the final 51 aa increases the contractile response of cultured cardiac cells to cholinergic signals. In both heterozygous and homozygous mutant mice derived from these mESCs, the same Akap10 disruption increases the cardiac response to cholinergic signals, suggesting a dominant interfering effect of the Akap10 mutant allele. The mutant mice have cardiac arrhythmias and die prematurely. We also found that a common variant of AKAP10 in humans (646V, 40% of alleles) was associated with increased basal heart rate and decreased heart rate variability (markers of low cholinergic/vagus nerve sensitivity). These...
Proceedings of the National Academy of Sciences, 2014
Significance Hearing impairment is most frequently caused by the loss of sensory hair cells in th... more Significance Hearing impairment is most frequently caused by the loss of sensory hair cells in the cochlea. One potential means of alleviating hearing loss is to restore these cells, which do not naturally regenerate in mammals. The zebrafish lateral line serves as a useful model for studying hair-cell regeneration because in this system there exist progenitors, mantle cells, from which hair-cell precursors originate. We have produced zebrafish with fluorescently labeled mantle cells, isolated those cells by flow cytometry, and analyzed the transcripts that they express. We have also defined the temporal window during which mantle cells respond to hair-cell death. This approach has identified genes representing unexpected signaling pathways that may contribute to the development of treatments for hearing loss.
Proceedings of the National Academy of Sciences, 2007
Sudden cardiac death due to abnormal heart rhythm kills 400,000–460,000 Americans each year. To i... more Sudden cardiac death due to abnormal heart rhythm kills 400,000–460,000 Americans each year. To identify genes that regulate heart rhythm, we are developing a screen that uses mouse embryonic stem cells (mESCs) with gene disruptions that can be differentiated into cardiac cells for phenotyping. Here, we show that the heterozygous disruption of the Akap10 (D-AKAP2) gene that disrupts the final 51 aa increases the contractile response of cultured cardiac cells to cholinergic signals. In both heterozygous and homozygous mutant mice derived from these mESCs, the same Akap10 disruption increases the cardiac response to cholinergic signals, suggesting a dominant interfering effect of the Akap10 mutant allele. The mutant mice have cardiac arrhythmias and die prematurely. We also found that a common variant of AKAP10 in humans (646V, 40% of alleles) was associated with increased basal heart rate and decreased heart rate variability (markers of low cholinergic/vagus nerve sensitivity). These...
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Papers by Taeryn Kim