Dr Serajul Khan

RESEARCHER PROFILE

Postdoctoral Fellow Conjoint Lecturer, School of Medical Sciences, University of New South Wales
Honorary Research Fellow, Faculty of Medicine, University of Sydney

+61 2 9399 1889


Dr Serajul Khan is a vestibular researcher with a broad range of skills and interest including basic science and clinical investigation. He has used animal models (wild type, knockout and mutant mice) for investigating the neural mechanisms underlying vestibulo-ocular reflex, the fastest reflex response in human. Particularly, he seeks to understand vestibular plasticity mechanisms that boost residual function following acute trauma, disease or natural ageing of the vestibular organ. This work will contribute to the development of treatment options for the estimated 300,000 Australians with peripheral vestibular organ injury.

Dr Khan completed his PhD in Biomedical Sciences at the Faculty of Medicine, University of Sydney in 2008. He was recruited to a post-doctoral fellowship in 2009 by Eminent Professor Simon Gandevia, who is an internationally recognised pioneer in human motor control. Dr Khan followed this with a second post-doctoral position in vestibular physiology in 2012. Currently, he is co-supervising 3 PhD students and mentoring 2 research assistants.

Projects Dr Serajul Khan is currently involved with

CURRENT PROJECTS

Can high dose of vitamin C boost recovery after balance organ injury?

We will address loss of balance, a pressing health-related issue that affects quality of life in ~5% of the population. Once the balance organ is injured or degrades with age, no treatments restore function. We have identified a nerve-pathway crucial for balance system adjustment & self-repair. The sensitivity of this pathway can be increased with vitamin C. We will determine if vitamin C treatment can improve recovery after balance loss and potentially translate to the clinic.

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Can high dose of vitamin C boost recovery after balance organ injury?

The effect of enhanced vestibular efferent transmission on plasticity of the mammalian vestibulo-ocu

We have identified a nerve-pathway crucial for balance adjustment and self-repair. We will test a mouse type that has this pathway genetically made more sensitive to determine whether stimulation of this pathway is a viable approach to improving recovery after balance loss in humans.

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The effect of enhanced vestibular efferent transmission on plasticity of the mammalian vestibulo-ocular reflex (VOR)

A new mouse model that determines the effects of a unilateral vestibular prosthesis on vestibular pl

Much like a cochlear implant restores auditory function, a vestibular prosthesis restores balance function. It is not clear whether the limited results from vestibular prostheses is due the device not stimulating one component (the otoliths) of the vestibular system essential for self-repair.

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A new mouse model that determines the effects of a unilateral vestibular prosthesis on vestibular plasticity.

RESEARCH TEAM

ASSOC PROF MICHAEL SCHUBERT Honorary Senior Research Fellow

ASSOC PROF PHILLIP CREMER Honorary Senior Research Fellow

ASSOC PROF ALAN BRICHTA Honorary Senior Research Fellow

DR REBECCA LIM Honorary Research Fellow

Chris Todd

CHRISTOPHER TODD Research Assistant

WILLIAM FIGTREE Research Assistant

Tanvir Ahmed

TANVIR AHMED PhD student

David Grenet

DAVID GRENET PhD student

PUBLICATIONS

Unexpected factors affecting the excitability of human motoneurones in voluntary and stimulated contractions.

Khan SI, Taylor JL, Gandevia SC

Aging reduces the high-frequency and short-term adaptation of the vestibulo-ocular reflex in mice.

Khan SI, Hübner PP, Brichta AM, Smith DW, Migliaccio AA

Prevailing evidence indicates a relatively late life decline in human vestibulo-ocular reflex (VOR) function. Although mice are commonly used in mechanistic studies of vestibular function, it remains unclear whether aging produces a corresponding decline in VOR function in mice. We sought to determine how the baseline VOR and its short-term adaptation were affected by aging. We tested 8 young (3-month old) and 8 aged (30-month old-equivalent to a ∼80-year old human) C57BL/6 mice. We measured their VOR response to whole-body static tilts and during 0.1-10 Hz whole-body sinusoidal and transient rotations before and after VOR adaptation training. Our data revealed minimal differences in static counter-tilt response between young and aged mice, but a significant deficit in baseline VOR gain in aged mice during transient rotations. Moreover, aged mice had a significant decrease in short-term VOR adaptation, particularly for training that sought to decrease the VOR response.

The mammalian efferent vestibular system plays a crucial role in the high-frequency response and short-term adaptation of the vestibuloocular reflex.

Hübner PP, Khan SI, Migliaccio AA

Although anatomically well described, the functional role of the mammalian efferent vestibular system (EVS) remains unclear. Unlike in fish and reptiles, the mammalian EVS does not seem to play a role in modulation of primary afferent activity in anticipation of active head movements. However, it could play a role in modulating long-term mechanisms requiring plasticity such as vestibular adaptation. We measured the efficacy of vestibuloocular reflex (VOR) adaptation in α9-knockout mice. These mice carry a missense mutation of the gene encoding the α9 nicotinic acetylcholine receptor (nAChR) subunit. The α9 nAChR subunit is expressed in the vestibular and auditory periphery, and its loss of function could compromise peripheral input from the predominantly cholinergic EVS. We measured the VOR gain (eye velocity/head velocity) in 26 α9-knockout mice and 27 cba129 control mice. Mice were randomly assigned to one of three groups: gain-increase adaptation (1.5×), gain-decrease adaptation (0.5×), or no adaptation (baseline, 1×). After adaptation training (horizontal rotations at 0.5 Hz with peak velocity 20°/s), we measured the sinusoidal (0.2-10 Hz, 20-100°/s) and transient (1,500-6,000°/s(2)) VOR in complete darkness. α9-Knockout mice had significantly lower baseline gains compared with control mice. This difference increased with stimulus frequency (∼ 5% <1 Hz to ∼ 25% >1 Hz). Moreover, vestibular adaptation (difference in VOR gain of gain-increase and gain-decrease adaptation groups as % of gain increase) was significantly reduced in α9-knockout mice (17%) compared with control mice (53%), a reduction of ∼ 70%. Our results show that the loss of α9 nAChRs moderately affects the VOR but severely affects VOR adaptation, suggesting that the EVS plays a crucial role in vestibular plasticity.

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