Our current research interests concern both developing and aging brain function related to hearing and balance, neurodegeneration, and neuro-immune responses using murine transgenic models. More specifically, research in my laboratory is investigating how the regulation of calcium signaling contributes to hearing loss, development and maturation of sensory organs, and nerve regeneration.
Read below to learn more about our current projects.
Relevance and Background
Hearing loss affects a vast amount of people. Approximately 15% of Americans adults between the ages of 20 and 69 have high frequency hearing loss due to exposure to loud sounds and 50% of Americans over 75 years old are affected by presbycusis (https://www.nidcd.nih.gov/health/statistics). Although substantial progress has been made in determining the genetic and cellular functions disrupted by acquired hearing loss, comparatively little is known about its underlying causes. It is known that both noise-induced hearing loss (NIHL) and age-related hearing loss (ARHL) involve outer hair cell (OHC) loss and dysfunction. The OHCs are one of the most prominent targets of noise and aging defects. Loss of OHCs leads to elevated hearing thresholds, along with loss of cochlear frequency tuning. Studies in our laboratory have focused on the development, maturation, and aging of the OHCs.
Age-related hearing loss according to the International Organization for Standardization (ISO) 7029 standard. Shown are audiograms for females (A) and males (B). The x-axis displays the pure tone frequency (Hz) and the y-axis the hearing thresholds (dB HL). Each individual graph is representative of the median audiogram at a particular age (ranging from 20 to 70 years old, with increments of 10 years).
Cochlear Cross Section
Tonghui Ding, Aihui Yan, Ke Liu. What is noise-induced hearing loss? British Journal of Hospital Medicine, Sept 2019;80(9):525-529.
Our approach to helping solve this problem is through studying the function of a calcium binding protein, oncomodulin (Ocm), which is a member of the parvalbumin gene family. Its distribution is highly restricted, being mostly limited to a subset of sensory hair cells, specifically the OHCs, in the mammalian inner ear and elsewhere to a subset of immune cells (macrophages and neutrophils). Targeted deletion of Ocm in mice leads to hearing loss and to slowed or delayed nerve regeneration.
Investigating the timing and location of proteins involved in the neural development of the afferents and efferents in the organ of corti.
Investigating the effects of the loss of Oncomodulin, thus tight Ca2+ regulation, on age-related hearing loss and vestibular dysfunction.
Investigating the effects of the loss of Oncomodulin on the Ca2+ ion import and export pathways and their kinetics.
Noise & Inflammation
Investigating the TLR4 receptor signaling pathway and its inhibition in the presence or absence of Oncomodulin.