This career transitioning project will provide the opportunity, protected time and training for the PI to learn new techniques to translate findings i otoconia biology obtained by animal research to human cases of benign paroxysmal positional vertigo (BPPV) and other otoconial dysfunction. BPPV is the most common cause of vertigo in humans, but the molecular etiology is unknown. My laboratory has been systematically studying molecular mechanisms of otoconia formation, anchoring and maintenance in mice using protein biochemistry, gene targeting, histology (including ultrastructure), and other molecular and cellular techniques. Building on my prior research experience in mouse genetics, I propose to learn cutting-edge genetic and genomic technologies to identify genetic variants or mutations in otoconial genes that may cause or exacerbate recurrent BPPV in patients, with and without hearing loss. In addition, I will learn linkage analysis using familial BPPV cases. Given the high prevalence and debilitating nature of recurrent BPPV and other otoconial dysfunction, often dually inflicted by age-related hearing loss, these types of genetic and translational studies are overdue.
Otoconia-related balance deficits and vertigo are common, yet the molecular etiology of these conditions in humans is completely unknown. In fact, genes and proteins responsible for otoconia formation, maintenance and anchoring have been discovered only in recent years in animal studies. Through this research training program, I will acquire advanced tools to facilitate the identification of genetic contribution to such vestibular disorders.
Büki, Bela; Jünger, Heinz; Lundberg, Yunxia Wang (2018) Vitamin D supplementation may improve symptoms in Meniere's disease. Med Hypotheses 116:44-46 |
Yang, Liping; Xu, Yinfang; Zhang, Yan et al. (2018) Mechanism Underlying the Effects of Estrogen Deficiency on Otoconia. J Assoc Res Otolaryngol 19:353-362 |
Xu, Yinfang; Zhang, Yan; Lundberg, Yunxia Wang (2016) Spatiotemporal differences in otoconial gene expression. Genesis 54:613-625 |