Carl_Nelson

Carl Nelson

Lecturer/Senior Lecturer

School of Science & Technology

Staff Group(s)
Bioscience

Role

Dr Nelson is a Senior Lecturer in Pharmacology, who teaches on several modules within undergraduate and postgraduate Bioscience courses. He is the Pathway Leader for the Physiology & Pharmacology pathway within the BSc (Hons) Biological Sciences degree. He is also the Module Leader for the following modules:

  • Human Physiology (Level 4)
  • Physiology (Level 5)
  • Professional Skills in Pharmacology (Level 5)

His other academic responsibilities include:

  • Chair of the Bioscience Success for All working group.
  • Bioscience CERT Student Mentor coordinator.

Career overview

After completing a PhD in Pharmacology at the University of Leicester in 2005, Dr Nelson undertook postdoctoral research in Leicester, initially investigating phosphoinositide signalling in cultured hippocampal neurons (2005-2007) and then working in a multidisciplinary team investigating the regulation of arterial smooth muscle potassium channels by vasoactive agents (2007-2012). He then moved to the University of Nottingham to undertake a further period of postdoctoral research within the Division of Respiratory Medicine, elucidating the functional roles of genes associated with lung function (2012-2014). He took up his current position here at Nottingham Trent University in 2014.

Research areas

Current research areas:

1. Toll-like receptors and intercellular microRNA signalling in asthma.

Toll-like receptors (TLRs) are transmembrane pattern recognition receptors that play a key role in the early detection of pathogens and activation of the innate immune response. TLR7 and TLR8 both respond to short sequences of single-stranded RNA and are predominantly expressed in monocytes, macrophages and dendritic cells. Several studies have found a genetic association between asthma susceptibility and TLR7/8 and there is extensive evidence that TLR7/8 agonists might ameliorate experimental asthma.

MicroRNAs (miRNAs) are short, non-coding RNA sequences that are potent repressors of gene expression. They can also be actively exported from cells and taken up by neighbouring cells. Crucially, certain miRNAs are capable of activating TLR7/8. We have shown that a number of miRNAs known to be elevated in asthmatic individuals are capable of robustly activating human TLR8 (but not TLR7) in human THP-1 monocytes and THP-1-derived macrophages. We are currently investigating the functional implications of this novel intercellular signalling pathway, in particular for macrophage differentiation/polarisation and phagocytosis. In future, would like to establish how this might influence asthma susceptibility and disease progression, as factors such as macrophage polarisation are known to influence asthma outcomes.

2. β-blockers as novel asthma therapies.

Activation of β2-adrenoceptors (β2-ARs) in the airways has a profound bronchodilatory effect and agonists at these receptors form a mainstay in the management of asthma. However, in the long-term, stimulation of these receptors may exacerbate airway inflammation, by a currently poorly-described mechanism. In contrast, there is emerging evidence that chronic treatment with β2-AR antagonists (so-called ‘β-blockers’) can be beneficial in both mouse models of asthma and in small scale trials with asthmatic patients. However, little is currently understood about how these benefits occur. We are investigating the effects of long-term treatment with β-blockers on both the proteome (using high-resolution quantitative Mass Spec (SWATHTM-MS) analysis in collaboration with Dr David Boocock (John van Geest Centre, NTU)) and cell biology of human airway epithelial cells. The aim is to identify pathways associated with beneficial changes, allowing the development of drugs that target these beneficial pathways at the expense of others and facilitating the design of more effective asthma therapies.

3. The design of novel beta blockers for the retardation of breast cancer metastasis.

Epidemiological studies have shown a significant association between β-blocker usage and improved breast cancer patient outcome. These studies found that patients with triple negative breast cancer (TNBC) benefitted the most from simultaneous intake of β-blockers. The rationale for using novel β2-selective β-blockers as a therapy for basal TNBC derives from their capacity to inhibit catecholamine-induced activation of G protein-coupled β2-adrenoceptors that drive cancer cell signalling pathways and cancer cell migration. Additional data obtained from pre-clinical and epidemiological studies has led to the hypothesis that β2-selective blockers are key mediators in preventing BC progression, rather than the β1-selective or β12 non-selective counterparts. A panel of novel small molecules have recently been developed between Dr Amanda Miles (Jon van Geest Centre, NTU) and the synthetic chemistry laboratory of Prof John Wallis and Dr Chris Garner (Department of Chemistry and Forensics, NTU). Current work demonstrates that one of these novel compounds is able to significantly reduce the migration and invasion of breast cancer cells in vitro. We would now like to: (i) further investigate the novel compound’s biological effects and pharmacological profile (in collaboration with Dr Carl Nelson); (ii) investigate the metabolism and pharmacokinetic dynamics of the novel compound; before (iii) identifying its clinical utility in vivo. Furthermore, the synthetic chemistry component of the project is ongoing and concerns the preparation and purification of more of the most biologically active materials, as well as extending the family of drug candidates by making small molecular changes to the molecular structure of the lead. This interdisciplinary approach encompasses the range of skills needed in modern day drug development including computer aided drug design, chemical synthesis, receptor binding studies and subsequent biological testing of the compounds.

4. Novel Therapeutic Approaches for Stroke-Associated Infections

Stroke-associated infections (SAI) constitute a very common and serious complication affecting one third of stroke survivors and correlate with a poor outcome and increased mortality. There is now an increasing evidence that SAI have a strong correlation with stroke-induced impairment to the systemic immune response. Unfortunately, no effective treatment is currently available to mitigate this risk. Moreover, the results of two recent randomized phase III clinical trials using prophylactic antibiotics demonstrated no clear benefits. Therefore, we are interested to develop novel therapeutic approaches that can ameliorate the immune system dysfunction after stroke and thus could tackle SAI. This project is in collaboration with the University of Manchester and University of Edinburgh and will be co-supervised with Dr Zahraa Al-Alhmady (who will be the principal supervisor).

Opportunities arise to carry out postgraduate research towards an MPhil / PhD in the areas identified above. Further information may be obtained on the NTU Research Degrees website https://www.ntu.ac.uk/research/research-degrees-at-ntu.

If you have an interest in carrying out a PhD in any of the above research areas (or related areas), please feel free to contact me (carl.nelson@ntu.ac.uk) for further information.

External activity

Dr Nelson has peer reviewed papers for international scientific journals including the British Journal of Pharmacology, Biochemical Pharmacology, and the Journal of Pharmacology and Experimental Therapeutics.

Dr Nelson is a member of the British Pharmacological Society, The Biochemical Society and The Physiological Society.

Sponsors and collaborators

Current and recent research is being conducted with the support of The Physiological Society and in collaboration with researchers at the University of Leicester and University of Nottingham.

Publications

Differential regulation of β2-adrenoceptor and adenosine A2B receptor signalling by GRK and arrestin proteins in arterial smooth muscle. Nash, CA,  Nelson, CP, Mistry, R,  Moeller-Olsen, C,  Christofidou, E,  Challiss, RAJ,  Willets, JM, Cellular Signalling, 2018, 51: 86-98

Role of transglutaminase 2 in A1 adenosine receptor- and β2-adrenoceptor-mediated pharmacological pre- and post-conditioning against hypoxia-reoxygenation-induced cell death in H9c2 cells. Vyas FS, Nelson CP, Dickenson JM, Eur J. Pharmacol, 2018, 819:144-160

β2-adrenoceptor-induced modulation of transglutaminase 2 transamidase activity in cardiomyoblasts. Vyas FS, Nelson CP, Freeman F, Boocock DJ, Hargreaves AJ, Dickenson JM, Eur J. Pharmacol, 2017, 813:105-121

The Ser82 RAGE Variant Affects Lung Function and Serum RAGE in Smokers and sRAGE Production In Vitro. Miller S, Henry AP, Hodge E, Kheirallah AK, Billington CK, Rimington TL, Bhaker SK, Obeidat M, Melén E, Merid SK, Swan C, Gowland C, Nelson CP, Stewart CE, Bolton CE, Kilty I, Malarstig A, Parker SG, Moffatt MF, Wardlaw AJ, Hall IP, Sayers I, PLoS One, 2016, 11(10): e0164041

Defining the roles of arrestin2 and arrestin3 in vasoconstrictor receptor desensitization in hypertension. Willets JM, Nash CA, Rainbow RD, Nelson CP, Challiss RJ, American Journal of Physiology Cell Physiology, 2015, 309 (3) 179-89

Steady-state modulation of voltage-gated K+ channels in rat arterial smooth muscle by cyclic AMP-dependent protein kinase and protein phosphatase 2B. Brignell JL, Perry MD, Nelson CP, Willets JM, Challiss RAJ and Davies NW, PLoS One, 2015, 10 (3) e0121285

Ca2+ handling and sensitivity in airway smooth muscle: Emerging concepts for mechanistic understanding and therapeutic targeting. Koopmans T, Anaparti V, Castro-Piedras I, Yarova P, Irechukwu N, Nelson C, Perez-Zoghbi J, Tan X, Ward JPT, Wright DB, Pulmonary Pharmacology and Therapeutics, 2014, 29 (2), 108-20

GSTCD and INTS12 Regulation and Expression in the Human Lung. *Obeidat M, *Miller S, Probert K, Billington CK, Henry A, Hodge E, Nelson CP, Stewart CE, Swan C, Wain LV, Melén E, Ushey K, Hao K, Lamontagne M, Bossé Y, Postma DS, Tobin MD, Sayers I and Hall IP, PLOS One, 2013, 8 (9), e74630

HTR4 gene structure and altered expression in the developing lung.  *Hodge E, *Nelson CP, *Miller S, Billington CK, Stewart CE, Swan C, Malarstig A, Henry AP, Gowland C, Melén E, Hall IP and Sayers I, Respiratory Research, 2013, 14, 77

Principal role of the type 6 adenylate cyclase in K+-channel regulation and vasodilator signalling in vascular smooth muscle cells. Nelson CP, Rainbow RD, Brignell JL, Perry MD, Willets, JM, Davies NW, Standen NB and Challiss RAJ, Cardiovascular Research, 2011, 91 (4), 694-702

G protein-coupled receptor kinase 2 and arrestin2 regulate arterial smooth muscle P2Y-purinoceptor signalling. Morris GE, Nelson CP, Everitt D, Brighton PJ, Standen NB, Challiss RAJ and Willets JM, Cardiovascular Research, 2011, 89 (1), 193-203

Endothelin signalling in arterial smooth muscle is tightly regulated by G protein-coupled receptor kinase 2. Morris GE, Nelson CP, Standen NB, Challiss RAJ and Willets JM, Cardiovascular Research, 2010, 85 (3), 424-33

* authors contributed equally

See all of Carl Nelson's publications...

Press expertise

  • G protein-coupled receptors
  • Airway disease, including asthma
  • Cyclic AMP signalling
  • RNA-sensing toll-like receptors