Dr Mirna Mustapha

Dr Mirna MustaphaMRC Senior Fellow
Department of Biomedical Science
The University of Sheffield
Western Bank
Sheffield S10 2TN
United Kingdom

Room: B1 224 Alfred Denny building
Telephone: +44(0) 114 222 1082
Email: mirna.m@sheffield.ac.uk

Centre for Sensory Neuroscience

Hearing Research Group


Research interests

Our lab is interested in understanding the cellular and molecular mechanisms underlying peripheral auditory neuropathy. We utilize transgenic mouse models and a variety of cutting edge molecular, microscopic, and physiological approaches to understand cochlear neurogenesis, and neuropathy associated with congenital and age related hearing impairment.


Helen Keller

Research image 1

Deafness is a common health problem

Hearing impairment is the most frequently occurring sensorineural defect in humans. The sense of hearing originates in the cochlea, a structure in the inner ear. Information about timing, frequency, and intensity of sounds is transmitted from the hair cells in the cochlea to the brain via spiral ganglion neurons by converting sound waves into nerve impulses. Any disruptions in this sensory pathway could result in auditory neuropathy and hearing impairment.


Auditory neuropathy is a type of hearing impairment caused by a defect in the hair cells and/or their synapses (synaptopathy) or the spiral ganglion neurons (neuropathy). It can affect people of all ages, from birth (congenital) through adulthood (acquired or age–related). Genetically inherited auditory neuropathy can be either isolated or associated with a systemic neurodegenerative disorder such as Charcot-Marie-Tooth disease or Friedreich’s ataxia.


Auditory neuropathy can be diagnosed using hearing tests such as auditory brainstem response (ABR) and otoacoustic emissions (OAE). Auditory neuropathy is defined by an abnormal ABR reading together with a normal OAE reading. An abnormal ABR reading can be the result of damage to the auditory nerve pathway, including the inner hair cells, their connection to the nerve (synapses), and/or the nerve itself (spiral ganglion neurons).

Why we care

Cochlear implants are currently the standard of care for hearing impairment. However, cochlear implant performance relies on healthy spiral ganglion neurons. Therefore, knowledge of the exact site of dysfunction (i.e., whether the patient suffers from synaptopathy or neuropathy) would aid in assessing the benefit of this treatment for patients. There are currently no available clinical tests that can distinguish between cochlear synaptopathy and neuropathy, but molecular genetic diagnosis can. Our long-term goal is to identify genes that are involved in congenital and age-related cochlear synaptopathy and/or neuropathy. Identification of these genes will improve the clinical diagnosis and our understanding of the molecular mechanisms that regulate the innervation of the cochlea and that cause cochlear neuropathy.


Spiral Ganglion Neurons

Type I and Type II

The cochlea contains two types of SGNs, type I and type II, which innervate the inner (IHC) and outer (OHC) hair cells, respectively. These two types of neurons are structurally and functionally different.

Type I SGNs make up the majority of the SGNs, approximately 90-95%, and are the main cells to transmit complex sound information to the brain.

The remaining 5 to 10% of SGNs are type II neurons that make synapses with the OHCs, which act as sound amplifiers.

Research image 3

Maturation and maintenance of the SGNs and their synaptic connections with the hair cells involves coordinated processes of axonal growth, synapse formation, and pruning of excess synapses formed during development. These processes, important for establishing functional cochlear neural circuits, differ between type I and type II and among the different subtypes of type I SGNs. Yet, genes and pathways regulating synaptic maturations and maintenance are largely unknown.

Exploration of the genetic differences between type I and type II SGNs

To define the networks of genes that promote SGNs type I and type II-specific aspects of functional maturation, we have recently performed a comparison of SGNs using fluorescence-activated cell sorting followed (FACS) followed by a whole transcriptome microarray analysis.

This study contributes to the identification of several transcription factors, signaling molecules, and ion channels that are encoded by type I and type II-differentially expressed genes.

Research image 3

Exploration of the genetic differences between subtypes of type I SGNs

During development, each SGNs type I adopts specific morphological, molecular, and electrophysiological proprieties to enable them to interpret and transmit complex sounds stimuli. Recent studies suggest that different subtypes of type I SGNs differ in their vulnerability to age and/or noise induced degeneration or auditory neuropathy.

While this local heterogeneity is an important feature of the type I SGNs, it is still unclear whether it is determined by endogenous or exogenous factors. Our research aims to identity and investigate genes that define and maintain the functional heterogeneity of these different subtypes using single cell transcriptome analysis.





Image by Stacy Levichev

Our team

Details about the Mustapha lab group will be along shortly.


We are currently offering a POSTDOCTORAL POSITION

More information to follow.

Selected publications

  • Sundaresan S, Kong JH, Fang Q, Salles F, Wangsawihardja F, Ricci AJ, Mustapha M. Thyroid hormone is required for pruning, functioning and long-term maintenance of afferent inner hair cell synapses. Eur J Neurosci. 2015 Sep 19. doi:10.1111/ejn.13081. PubMed PMID: 26386265.
  • Fang Q, Indzhykulian AA, Mustapha M, Riordan GP, Dolan DF, Friedman TB, Belyantseva IA, Frolenkov GI, Camper SA, Bird JE. The 133-kDa N-terminal domain enables myosin 15 to maintain mechanotransducing stereocilia and is essential for hearing. Elife. 2015 Aug 24;4. doi: 10.7554/eLife.08627. PubMed PMID: 26302205.
  • Calton MA, Lee D, Sundaresan S, Mendus D, Leu R, Wangsawihardja F, Johnson KR, Mustapha M. A lack of immune system genes causes loss in high frequency hearing but does not disrupt cochlear synapse maturation in mice. PLoS One. 2014 May 7;9(5):e94549. doi: 10.1371/journal.pone.0094549. eCollection 2014. PubMed PMID: 24804771; PMCID: PMC4012943.
  • Mendus D, Sundaresan S, Grillet N, Wangsawihardja F, Leu R, Müller U, Jones SM, Mustapha M. Thrombospondins 1 and 2 are important for afferent synapse formation and function in the inner ear. Eur J Neurosci. 2014 Apr;39(8):1256-67. doi: 10.1111/ejn.12486. Epub 2014 Jan 27. PubMed PMID: 24460873; PMC4132060.

Full publications