Dr Mohammed A. Nassar
Room: C223 Alfred Denny building
Brief career history
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.
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..
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.
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.
Undergraduate and postgraduate taught modules
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:
- Mohammed ZA, Doran C, Grundy D & Nassar MA (2017) Veratridine produces distinct calcium response profiles in mouse Dorsal Root Ganglia neurons. Scientific Reports, 7. View this article in WRRO
- Hoffmann T, Kistner K, Carr RW, Nassar MA, Reeh PW & Weidner C (2017) Reduced excitability and impaired nociception in peripheral unmyelinated fibers from Nav1.9-null mice. PAIN, 158(1), 58-67.
- Nassar M, Christian Weidner , Peter W Reeh & Tal Hoffmann (2016) Use dependence of peripheral nociceptive conduction in the absence of TTXr sodium channel subtypes. Journal of Physiology, 594(19), 5529-5541.
- Denk F, Ramer LM, Erskine ELKS, Nassar MA, Bogdanov Y, Signore M, Wood JN, McMahon SB & Ramer MS (2015) Tamoxifen induces cellular stress in the nervous system by inhibiting cholesterol synthesis. Acta Neuropathologica Communications, 3(1). View this article in WRRO
- Doran C, Chetrit J, Holley MC, Grundy D & Nassar MA (2015) Mouse DRG Cell Line with Properties of Nociceptors. PLOS ONE, 10(6). View this article in WRRO
- Zhang Q, Chibalina MV, Bengtsson M, Groschner LN, Ramracheya R, Rorsman NJG, Leiss V, Nassar MA, Welling A, Gribble FM , Reimann F et al (2014) Na + current properties in islet α- and β-cells reflect cell-specific Scn3a and Scn9a expression. The Journal of Physiology, 592(21), 4677-4696.
- Minett MS, Falk S, Santana-Varela S, Bogdanov YD, Nassar MA, Heegaard A-M & Wood JN (2014) Pain without nociceptors? Nav1.7-independent pain mechanisms.. Cell Rep, 6(2), 301-312. View this article in WRRO
- Minett MS, Nassar MA, Clark AK, Passmore G, Dickenson AH, Wang F, Malcangio M & Wood JN (2012) Distinct Nav1.7-dependent pain sensations require different sets of sensory and sympathetic neurons. Nature Communications, 3. View this article in WRRO
- Zhao J, Lee M-C, Momin A, Cendan C-M, Shepherd ST, Baker MD, Asante C, Bee L, Bethry A, Perkins JR , Nassar MA et al (2010) Small RNAs control sodium channel expression, nociceptor excitability, and pain thresholds.. J Neurosci, 30(32), 10860-10871.
- (2010) Nociceptor-expressed ephrin-B2 regulates inflammatory and neuropathic pain. Molecular Pain, 6. View this article in WRRO
- Abrahamsen B, Zhao J, Asante CO, Cendan CM, Marsh S, Martinez-Barbera JP, Nassar MA, Dickenson AH & Wood JN (2008) The cell and molecular basis of mechanical, cold, and inflammatory pain.. Science, 321(5889), 702-705.
- Nassar MA, Baker MD, Levato A, Ingram R, Mallucci G, McMahon SB & Wood JN (2006) Nerve injury induces robust allodynia and ectopic discharges in Na
v1.3 null mutant mice. Molecular Pain, 2. View this article in WRRO
- Braz JM, Nassar MA, Wood JN & Basbaum AI (2005) Parallel “Pain” Pathways Arise from Subpopulations of Primary Afferent Nociceptor. Neuron, 47(6), 787-793.
- Nassar MA, Levato A, Stirling LC & Wood JN (2005) Neuropathic Pain Develops Normally in Mice Lacking both Na v 1.7 and Na v 1.8. Molecular Pain, 1, 1744-8069-1-24-1744-8069-1-24. View this article in WRRO
- Stirling CL, Forlani G, Baker MD, Wood JN, Matthews EA, Dickenson AH & Nassar MA (2005) Nociceptor-specific gene deletion using heterozygous NaV1.8-Cre recombinase mice. Pain, 113(1), 27-36.
- Nassar MA, Stirling LC, Forlani G, Baker MD, Matthews EA, Dickenson AH & Wood JN (2004) Nociceptor-specific gene deletion reveals a major role for Nav1.7 (PN1) in acute and inflammatory pain. Proceedings of the National Academy of Sciences, 101(34), 12706-12711.