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.

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 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

 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

Our research focuses on investigating the changes in excitability of nociceptors in response to noxious stimuli. Intense chemical, mechanical or thermal stimulation of sensory neurons in the dorsal root ganglion (DRG) results in the perception of pain and subsequent activation of certain reflex responses to mitigate tissue damage. Short-lived pain is evolutionarily advantageous as it serves as a deterrent and warning signal, however the desire to therapeutically alleviate chronic pain following trauma and illness has driven research into this field. A more informed understanding of excitability changes will allow us to screen for drugs that reverse these and thereby prevent the activation of nociceptors and pain signal.

To investigate excitability changes we use a functional assay that we recently developed, see figure 1 below [1]. Our assay is simple to carry out yet provides a wealth of information about the properties of pain neurons. The assay allows us to sample a large number of neurons efficiently. Our assay has several applications, see figure 2 below [2], but we are currently focusing on the two described below.

Figure 01

Figure 1: Our assay for the assessments of the excitability of pain and non-pain neurons
Sensory ganglia contain a heterogeneous population of neurons. Pain neurons are typically small in size and respond to painful stimuli. Most pain neurons responded to veratridine (which activate voltage-gated sodium channels) with an Oscillatory (OS), Rapid decay (RD) or Intermediate decay (ID) profiles. Non-pain neurons are typically large in size and do not respond to painful stimuli. Most non-pain neurons respond to veratridine with a Slow decay (SD) profile. The percentages of the OS and SD veratridine profiles plus the percentage of veratridine-irresponsive neurons can be used for an efficient assessment assay of the excitability DRG neurons. Changes in the SD population reflect changes in non-nociceptors (blue, typically 15-20% of all neurons). Changes in the OS population (red, typically 30-40% of all neurons) reflect changes in nociceptors. Changes in the veratridine-irresponsive population (grey, typically 30-40% of all neurons) can reflect sensitisation of high threshold and normally “silent” neurons.

Figure 02

Figure 2: Applications of the veratridine-based calcium assay
his assay is a very efficient method to characterise changes in a heterogeneous population of neurones, therefore has the potential for several applications. One of these is the identification of lead analgesic drugs, through hit validation in cell line-based screens on all types of DRG neurones, or hit identification by a direct screen of specific DRG neurones. It can also assess how stem cell-derived neurones compare to primary neurones of the same type, more efficiently than by patch clamping.

Generating neurones from patients’ IPSC with unknown genetic mutations, and comparing these to neurones with established changes in DNA can aid in diagnostics. The assay is suited to characterise neuronal pathologies that develop over time, as in diabetes, ageing or cancer. Lastly, the assay is valuable for the International Mouse Phenotyping Consortium, the aim of which is to phenotype 20,000 knockout mouse transgenic lines, some of which focusing on changes in DRG.


Application 1: Investigation of changes in the excitability of pain neurons in diabetes 

We are interested in characterising diabetes-induced changes in the excitability of pain neurons. Diabetes is on the increase worldwide and peripheral neuropathy is one of the most common complications. Diabetic neuropathy causes pain. We are currently studying the changes in the excitability of pain neurons in the db/db mouse model.

Application 2: Drug screening for effective and safe reduction of the excitability of pain neurons 

We are interested in identifying novel compounds or combination of existing compounds that produce the biggest reduction in the excitability of pain neurons with minimal effect on non-pain neurons. This should produce effective analgesia in vivo with minimal side effects. We screen candidate compounds on cultured primary mouse DRG neurons.

We welcome master and PhD students interested in taking part in our research

Please email me at m.nassar@sheffield.ac.uk for current projects and an informal chat. We are also happy to collaborate with other scientists who share our interests.

References

1. Mohammed, Z.A., et al., Veratridine produces distinct calcium response profiles in mouse Dorsal Root Ganglia neurons. Sci. Rep, 2017. 7: p. 45221.
2. Mohammed, Z., K. Kaloyanova, and M.A. Nassar, An unbiased and efficient assessment of excitability of sensory neurons for analgesic drug discovery. Pain, 2020.

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
  • BMS303 Molecular Physiology of Ion Channels
  • BMS319 Pharmacological Techniques
  • Level 3 Practical and Dissertation Modules

Masters (MSc):

  • BMS6084 Pharmacological Techniques
Opportunities

Postgraduate studentship opportunities

Project 1: Investigation of changes in the excitability of pain neurons in diabetes
Diabetes is a condition in which a person’s homeostatic mechanism to control blood sugar level is compromised, resulting in an inability to produce insulin and reduce sugar level. The incidence of diabetes is increasing worldwide, and peripheral neuropathy is one of the most common complications.
Diabetic neuropathy causes extreme pain. The cause of this is thought to be from microvascular injury of the vasa nervorum, the blood vessels which supply nerves. The resulting neuronal damage is thought to affect nociceptor excitability and make them more likely to respond to stimuli. We are interested in characterising diabetes-induced changes in nociceptor excitability. Our research is currently focusing on the pain neurones of the db/db knockout mouse model.

Project 2: Drug screening for effective and safe reduction of the excitability of pain neurons
Our aim is to identify novel compounds, or a combination of existing compounds, that produce the biggest reduction in the excitability of pain neurons with a minimal effect on non-nociceptors. By targeting only nociceptor activity, this should produce effective analgesia in vivo, with minimal side effects. The initial step of this process is to screen candidate compounds on cultured primary mouse DRG neurons. Only those which produce the desired effect are taken for further investigation.

References
1. Mohammed, Z.A., et al., Veratridine produces distinct calcium response profiles in mouse Dorsal Root Ganglia neurons. Sci. Rep, 2017. 7: p. 45221.
2. Mohammed, Z., K. Kaloyanova, and M.A. Nassar, An unbiased and efficient assessment of excitability of sensory neurons for analgesic drug discovery. Pain, 2020.

For further information on project studentships, please see the PhD opportunities (Funded or Self-Funded) on FindAPhD.com

We welcome Master and PhD students interested in taking part in our research.

Please email me at m.nassar@sheffield.ac.uk for current projects and an informal chat. We are also happy to collaborate with other scientists who share our interests.

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

PhD Opportunities

Selected publications

Journal articles