Meniere's Disease  Neuroscience Group

Vibha Patil

Postdoctoral Research Associate

Yolanda Liu

Research Assistant

Prathamesh Nadar Ponniah

Research Fellow

Kristina Markova

Postdoctoral Research Associate

Tanvi Hussain - Master Student

Jacob Pogson - Senior Audiologist

Tom Comford - Honours Student

Pablo Cruz Granados - Honours Student

Sayedali Mohseni - Masters Student (Data Science Intern)

Anvitha Peddada  - Masters Student (Data Science Intern)

Maniratnam (Mani) Meka - - Masters Student (Data Science Intern)

Meniere’s disease Consortium, network of clinical centres in Europe

Explore the links below:

• TIGER 
• UNITI

Current projects:

Deciphering the genetics and inflammatory bases of Meniere’s disease and Tinnitus Disorder by combining multi-omic data and 3D cellular models.

Meniere's disease is the third most common cause of episodic vertigo after benign paroxysmal positional vertigo and vestibular migraine in neurotology clinics. It is considered a rare and debilitating disease within the general population.

It is a multifactorial inner ear disorder characterized by episodes of spontaneous vertigo, associated with tinnitus, and fluctuating sensorineural hearing loss. It is a heterogeneous condition with a variable phenotype associated with other comorbidities such as migraine, several autoimmune and autoinflammatory disorders, including allergies.

According to epidemiological and genetic data, the condition has a significant genetic contribution. Familial MD is observed in 6-10% of cases and rare mutations in OTOG, MYO7A and TECTA genes have been found in several unrelated families. Although most patients are considered sporadic, hidden recessive inheritance and de novo mutations are emerging as causative in Meniere's Disease, and genetic diagnosis is being implemented.

Genetic modelling of Meniere disease

We have established an auditory and vestibular phenotyping laboratory at the Kolling Institute. We are working with a preclinical model to assess the functional role of human mutations found in Spanish families with Meniere disease, including OTOG-mediated compound recessive inheritance and MYO7A-mediated loss of function Meniere disease.

Understanding the immune response in Meniere disease

Patients with Meniere's disease  show a persistent systemic inflammatory status, proinflammatory cytokines released by monocytes (IL-1β and TNF-α), and high levels of CCL2, IL-4, and IgE, support a disorder in the immune response with several immunophenotypes. Some patients with an autoinflammatory phenotype mediated by IL-1β, while others show an autoimmune profile driven byTNF-α and usually associated with autoimmune thyroid disease or systemic rheumatoid disorders. Moreover, a relevant group of individuals have a persistent type 2 immune response with IL-4, IL-13, and IL-6 with high levels of IgE. By combining single cell transcriptomics and proteomics, we are starting to define the molecular signals driving each immunophenotype.

Therefore, genetic factors and innate/adaptive immune responses play a central role in the pathophysiology of the condition.

Tinnitus is the perception of a phantom sound that affects between 10 and 15% of the general population. Furthermore, 1–3% of the population can be diagnosed with a debilitating tinnitus disorder, a condition associated with sleep disturbance and psychological distress, with emotional and behavioral consequences with a significant impact on health-related quality of life.

Despite this high burden for the health system, treatments for tinnitus are presently lacking since the heterogeneity of the tinnitus patients represents a major barrier to the development of effective tinnitus therapies. Tinnitus is not only a symptom associated with hearing loss, but it is also considered the result of exacerbated plasticity of the central auditory system in response to the crosstalk with auditory nerve fibers.

The development of tinnitus is related to different nuclei of the auditory pathway, particularly the cochlear nuclei and the primary auditory cortex. The perception of tinnitus involves different brain areas and neural networks in which other structures such as the hippocampus or prefrontal cortex. Likewise, it can involve unknown auditory and non-auditory networks and molecular pathways. This complex combination has hampered advancements in the field and the identification of a genetic contribution to tinnitus has been at the forefront of tinnitus research in the last five years.

Potential PhD projects 
1. Identification and validation of novel genes in Meniere disease by comprehensive analysis of coding and non-coding regions in the human genome. 
2. Role of mobile elements in the genetic architecture of Meniere disease and tinnitus disorder 
3. Audiovestibular phenotyping of a transgenic OTOG mouse model of Meniere disease 
4. Single cell multiome analysis of immune response in Meniere disease patients 
5. Tonotopic epigenetic profiling in the mouse cochlea 
6. Genetic and epigenetic biomarkers of severe tinnitus

The Meniere’s Disease Neuroscience Program is an initiative of the University of Sydney to investigate the cellular and molecular bases of this condition and to identify molecular targets to develop personalised treatments.

Our laboratory is located at the Kolling Institute, level 11, and will join the expertise of the Otology and Neurotology Group at the University of Granada with the added value of new laboratory members to develop an ambitious international multidisciplinary research program. The team will combine clinical and human multi-omic data (genomic, epigenomic, transcriptomics) and cellular and animal models to reveal the molecular mechanisms leading to Meniere's Disease and severe tinnitus. 

The University of Sydney - Professor Jose Antonio Lopez-Escamez