Dr Mohammed A. Nassar

Dr Mohammed A. NassarLecturer
Level 1 Tutor

Department of Biomedical Science
The University of Sheffield
Western Bank
Sheffield S10 2TN
United Kingdom

Room: C223 Alfred Denny building
Telephone: +44 (0) 114 222 2392
Email: m.nassar@sheffield.ac.uk

Neuroscience


General

Brief career history

  • 2010-present: Lecturer, dept. of Biomedical Science, Sheffield University, UK.
  • 1999-2009: Senior postdoctoral Fellow, Molecular Nociception Group, Dept. of Biology, UCL, UK.
  • 1998-99: Postdoctoral Fellow (Wellcome Prize Fellowship), Wellcome Laboratory for Molecular Pharmacology, Dept. of Pharmacology, UCL, UK.
  • 1994-98: Postgraduate student (Wellcome Prize studentship), Wellcome Laboratory for Molecular Pharmacology, Dept. of Pharmacology, UCL, UK.
  • 1994: Research assistant in the Wellcome Laboratory for Molecular Pharmacology, Dept. of Pharmacology, UCL, UK.

Research interests

My research is focused on primary sensory neurons which are part of the peripheral nervous system (PNS). Sensory neurons convey sensory information from the both the internal (e.g. viscera, muscles and bones) and the external (skin) environments to the central nervous system (CNS).

Sensory neurons convey both innoxious and noxious stimuli. The latter is perceived in the CNA as pain. Inflammation and nerve injury sensitise sensory neurons which results in decreased pain thresholds. My research interest lies in investigating the molecular changes in sensory neurons that are associated with pathological pain.

This is important in order to identify potential targets for new, effective and specific analgesic drugs. My lab uses a variety of methods based on molecular biology, cellular biology and functional assays.

Professional activities

  • 2015: Postgraduate Certificate in Learning and Teaching from the University of Sheffield (Fellow of The Higher Education Academy, FHEA)

Full publications list

Research

General Aim: Elucidating the molecular mechanisms of sensitisation of sensory neurons in pain.

To achieve the general aim above, research in my lab is organised around three projects. The first project investigates the regulation of the plasma membrane pool of the channel Nav1.7. I was the first to reveal the crucial role of Nav1.7 in pain signalling (Nassar, PNAS 2004). Since then Nav1.7 has been shown to underlie three genetic pain disorders in humans; these are primary erthromyalgia, familial rectal pain and complete insensitivity to pain.

However, little is known about how the Nav1.7 surface pool is regulated to set pain thresholds and respond to changes in the environment (e.g. inflammation). Nav1.7 surface pool is determined by mechanisms controlling its transport to nerve terminals, insertion into and endocytosis from the membrane. Investigation of these processes may lead to new druggable targets for pain relief. We employ several approaches to investigate Nav1.7 trafficking, these include generation of GFP-tagged Nav1.7 channel, generation of reporter proteins containing parts of the Nav1.7 channel, super-resolution microscopy and a proteomic characterisation of proteins that interact with Nav1.7..

Figure 01

The second project evaluates the use of a VGSC channel opener or “agonist” called Veratridine and calcium imaging to provide a high throughput assay to assess the excitability of sensory neurons. We were the first to characterise Veratridine responses in cultured sensory neurons (Mohammed, Sci Rep 2017). We found that Veratridine produces distinct response-profiles in cultured sensory neurons that map to known functional neuronal subtypes.

Therefore, these response-profiles allow a simple identification of nociceptive neurons (pain sensing) and non-nociceptive neurons. Changes in the properties of these profiles reflect changes in the excitability of sensory neurons. We are currently investigating how Veratridine profiles can be used to assess the activity of two important sodium channels, Nav1.7 and Nav1.8, in sensory neurons. This may provide a biologically relevant yet high throughput assay to screen for blockers for these channels. This project involves the use of calcium imaging on cultured sensory neurons.

Figure 02

The third project aims to provide a new in vitro model of sensory neurons to replace the use of primary sensory neurons. Primary sensory neurons form rodents are the standard in vitro model used in pain research. However, the number of neurons that can be obtained from one animal is limited and is insufficient for molecular and biochemical experiments. Furthermore, sensory neurons cultures contain a variety of cell types including glia and fibroblasts, making it difficult to interpret data from biochemical studies.

Therefore, the generation of an immortal cell line from sensory neurons will lead to experiments being carried out that would not have been possible with primary cultures. Equally important, a cell line will replace the use of rodents to obtain primary cultures which will reduce the number of animals used in research. My lab has generated a DRG-derived cell line (MED17.11) that can be propagated in culture indefinitely (Doran et al, 2015). The cell line can be differentiated to express DRG markers. The project aims to improve the differentiation protocol to produce sensory neurons of an adult phenotype. This cell line may provide a new in vitro model that is useful for drug screens.

Figure 03

Teaching

Teaching experience:

  • 2015: Postgraduate Certificate in Learning and Teaching from the University of Sheffield (Fellow of The Higher Education Academy, FHEA)

Undergraduate and postgraduate taught modules

Undergraduate:

  • BMS109 Cell & Molecular
  • BMS109 Practical Classes
  • BMS110 Research Topics in Biomedicine
  • BMS242/3 Practical Classes
  • BMS303 Molecular Physiology of Ion Channels
  • BMS319 Pharmacological Techniques
  • Level 3 Practical and Dissertation Modules

Masters (MSc):

  • BMS6084 Pharmacological Techniques
Opportunities

Postgraduate studentship opportunities

We advertise PhD opportunities (Funded or Self-Funded) on FindAPhD.com

For further information and details of other projects on offer, please see the department PhD Opportunities page:

PhD Opportunities

Selected publications

Journal articles