I. Profile
Otological Genetic Diseases Laboratory (hereinafter referred to as the Laboratory) was approved for establishment by Shandong Provincial Department of Medicine and Health in May 2013. It is an important project of the Provincial Department of Health to promote scientific research and health construction. The overall goal of the laboratory is to use hereditary mouse models to research the mechanism of deafness, seek interventions or treatments for hearing loss, achieve rapid transformation of basic research results into clinical applications, and contribute to the prevention, diagnosis and treatment of otological genetic diseases. In recent years, it has undertaken more than 20 scientific research projects, including 9 projects from the National Natural Science Foundation of China, and published more than 40 SCI papers.
II. The Team
The head of the Laboratory is Professor Han Fengchan, PhD of medicine, doctoral advisor, member of the International Otolaryngology Research Association (ARO), and the Director of the Shandong Provincial Key Laboratory of Medicine and Health Otological Genetic Diseases. In 1998, he received a doctorate degree in biochemistry and molecular biology from the Fourth Military Medical University. In June 2001, he was a postdoctoral fellow at the National University of Singapore School of Medicine. From 2007 to 2011, he was a visiting scholar at the Department of Genetics and Otolaryngology at School of Medicine, Case Western Reserve University. Mainly engaging in the research on the molecular mechanism and intervention of hereditary deafness, he has discovered and named the erl mouse deafness gene mutation site, and successfully treated mice with hereditary deafness with drugs for the first time, established and identified a variety of hereditary deaf mouse models, and screened a variety of drugs for hearing to improve age-related deafness of mice. The achievements are expected to provide new ways for the prevention and treatment of age-related deafness in humans. He has won as the major contributor 3 provincial and ministerial science and technology progress awards, 2 national new drug certificates, undertaken 12 national, international and provincial and ministerial research projects (including 3 general projects of the National Natural Science Foundation of China), published more than 50 academic papers, including more than 30 SCI papers.
The Laboratory has established an academic committee with Professor Wang Haibo as the Director. The members include Professor Xu Anting, Professor Song Xicheng, Professor Han Fengchan, Professor Liu Tingyan, Professor Ma Xiufang, Dr. Shang Wenjing, and Dr. Ma Ying, all of whom are senior level experts in the same field at home and abroad. The Laboratory currently has more than 10 scientific and technical personnel including academic backbones and full-time experimental personnel. The team has a reasonable structure of age, education and professional titles, and more than 90% of the staff have master's or doctoral degrees.
III. Academic Achievements
The research directions that the Laboratory has formed include: the study of model animals (hearing and balance), the mechanism and intervention of hereditary deafness, and the biomechanical study of hearing and balance.
1. Construction of mouse models of hereditary hearing and balance disorders
It is using ENU mutagenesis and gene knockout techniques (such as TALEN and CRISPR-Cas9, etc.) to construct a variety of genetic deaf mouse models: erl mutagenic aging deaf mice, Ush1c knockout mice with hearing and balance disorders, Fscn2 knockout mice with progressive deafness and Tyk2 knockout mice with hereditary deafness, etc. Efforts has been made in screening and identifying mouse models of age-related deafness such as B6, A/J, DBA/2J, NOD/LtJ, etc. In addition, a variety of hereditary mouse otitis media (OM) models were screened and identified, and it was found that Phex, Tlr2, Cdh7, and Sh3pxd2 gene mutations can lead to the occurrence of mouse OM. It provides a useful tool for the basic research of hereditary deafness.
2. Research on the Mechanism and Intervention of Hereditary Deafness
Based on the establishment and identification of mouse models of hereditary deafness, it has been found that free radical damage, endoplasmic reticulum stress and cell apoptosis are the cause of age-related deafness model mice (erl, DBA/2J, A/J, etc.). An important cause of hearing loss, Z-VAD-FMK, EPO, NGF, tauroursodeoxycholic acid, ethosuximide and α-lipoic acid, etc. can lower the hearing threshold of mice with aging deafness and reduce the pathological damage of the cochlea. This provides an experimental basis for clinical drug treatment of age-related deafness.
3. Biomechanical Study and Clinical Application of Meniere's Disease Pathogenesis
It has been discovered that the Phex gene mutant mouse is an ideal mouse model for studying Ménière’s syndrome. The basic ideas and techniques of biomechanics research are applied to the study of hearing and balance function mechanisms. The mechanics of sound transmission of the inner ear and the mechanics of the balance of the vestibular system provide experimental basis for the study of its pathogenesis and the formulation of treatment plans.
4. Main Research Results
Research results are mainly in the form of papers in Neuroscience, ASN Neuro, Hear Res, Pharmacogenomics J, BBRC, Cell Death & Disease, Int J Mol Med, J Neurosci Res, Pharmacogenomics J, Infect Immun, Plos One, AM J Pathol, Genes Genomes Genetics , Archives of Biochemistry & Biophysics and other journals.
IV. Infrastructure
At present, the Laboratory has begun to take shape, and the construction of 5 main experimental platforms has been completed, including: 1. Audiology experimental platform: development of Otoscopy, ABR and DPOAE and other ear science detection technologies; 2. Molecular biology experimental platform: development of genes typing, gene quantification (quantitative PCR instrument), molecular cloning, molecular hybridization, expression profiling (Simple Western) and other technologies; 3. Cell biology experiment platform: establishing a cell biology laboratory to study changes in cell signal transduction channels caused by gene mutations; 4. Morphology experiment platform: tissue cell morphology analysis, such as cell smears, tissue sections, HE staining and immunohistochemistry, etc.; 5. Experimental platform for mouse models of hereditary deafness: providing a variety of mouse models of hereditary deafness for experimental use through methods such as gene knockout, gene mutagenesis and phenotype screening.
