Dr Richard Billington
Profiles

Dr Richard Billington

Associate Professor of Biology

School of Biological and Marine Sciences (Faculty of Science and Engineering)

Role

Radiation Protection Supervisor
Marketing lead Biological Sciences

My background is in Biochemistry and Biochemical Pharmacology and I am particularly interested in signalling pathways that involve pyridine nucleotides. My interests also extend to many other areas as Biochemical techniques can be used to study a huge array of processes.

I am also a Biologist with particular interests in birds, mammals (terrestrial and marine), reptiles, medicinal plants and a number of invertebrate groups including Odonata, Isopods, Shieldbugs, Bees, Butterflies and whatever else happens to be a nice small group with a good ID book/key that not many people are interested in. I am currently interested in linking invertebrate biochemistry to ecological studies and using lab based techniques to compliment ecological studies.


Qualifications

Degree:
1996-1999 Biochemistry, University of Bristol
PhD: 
1999-2002 Department of Pharmacology, University of Cambridge
Postdoc:
2002-2003 Department of Pharmacology, University of Cambridge (Biotechnology and Biological Sciences Research Council) 2003-2005 Università degli Studi del Piemonte Orientale. 
Teaching

2006-2008 “Ricercatore” at the Università degli Studi del Piemonte Orientale, Novara, Italy.

Research interests

Pyridine nucleotides and their roles in basic metabolism and signalling

NAD(P) has long been thought of as a simple redox co-factor involved in basic metabolism but recent findings show that it is also involved in cell signalling pathways. These pathways include fundamental processes such as gene expression (via the Sirtuin enzymes), DNA repair (via PARP; poly ADP-ribose polymerase), posttranslational protein modification (via PARP and ADP-ribosyl tranferases; ART) and Ca2+-signalling (via CD38 metabolites). Furthermore, it has been shown that the maintenance of high intracellular NAD levels can prolong the lifespan of cells probably in a Sirtuin-dependent manner. Many of these roles have been elucidated only recently and we are still only beginning to understand the wide-ranging implications that pyridine nucleotide signalling may have in the cell. My research is aimed at elucidating some of the fundamental processes which control and are controlled by pyridine nucleotides and their derivatives.

Pyridine nucleotide homeostasis as a pharmacological target

The widespread involvement of NAD(P) in signalling pathways has also led to the hypothesis that such NAD(P)-mediated processes and NAD(P) homeostasis pathways could be promising drug targets for a wide range of diseases, in particular cancer and diabetes but also neurodegeneration, obesity and psoriasis to name a few. Although we are still some way off the clinical use of such drugs, my research aims to highlight novel targets and mechanisms that could provide therapeutics in the future.

Ca2+-signalling with particular respect to pyridine nucleotide second messengers.

The enzyme CD38 is a multifunctional cell surface enzyme and receptor. Two of its enzymatic products, cADPR and NAADP (metabolites of NAD and NADP), have been shown to be potent releasers of intracellular Ca2+ via the Ryanodine receptor and Two Pore Channels (TPC) respectively. Little is know still about the mechanisms that control the actions of these two messengers and my research is aimed at elucidating these mechanisms.

The generation of specificity/complexity and its decoding in signalling pathways.

Cell signalling pathways must specifically control only selected target proteins. Indeed, many disease states are caused by the inappropriate or dysregulated activation of non target proteins. In order to acheive this, cellular signals must necessarily include a certain level of complexity (for instance variation of the spatial and temporal parameters). There is still much to understand about how levels of complexity are both encoded and decoded such that only specific targets respond.

Immune function in invertebrates

Invertebrates lack an adaptive immune system such as that found in mammals and must rely on their innate mechanisms for combatting pathogens and parasites. I am interested in the biochemistry of the mechanisms applied by invertebrates to achieve this and linking immune function to ecology and rarity.



Invasive species

Invasives have always been fascinating to me and I am interested in spread and survival of such species, mostly with terrestrial invertebrates. My definition of invasive is lax and I also include colonising species

Key publications are highlighted

Journals
Articles
Hanley M, sanders S, Stanton H-M, Billington R & Boden R 2019 'A pinch of salt: response of coastal grassland plants to simulated seawater inundation treatments' Annals of Botany , DOI PEARL
Cioffi R, Moody AJ, Millán A, Billington RA & Bilton DT 2016 'Physiological niche and geographical range in European diving beetles (Coleoptera: Dytiscidae)' Biology letters 12, (6) , DOI PEARL
Al-Shabany AJ, Moody AJ, Foey AD & Billington RA 2016 'Intracellular NAD+ levels are associated with LPS-induced TNF-α release in pro-inflammatory macrophages' Bioscience Reports 36, (1) , DOI PEARL
Almzaiel AJ, Billington R, Smerdon G & Moody AJ 2015 'Hyperbaric oxygen enhances neutrophil apoptosis and their clearance by monocyte-derived macrophages' Biochemistry and Cell Biology 93, (4) 405-416 , DOI
Hawar S, Vevers W, Karieb S, Ali BK, Billington R & Beal J 2013 'Biotransformation of patulin to hydroascladiol by Lactobacillus plantarum' FOOD CONTROL 34, (2) 502-508 Author Site , DOI
Al-Abady ZN, Durante B, Moody AJ & Billington RA 2013 'Large changes in NAD levels associated with CD38 expression during HL-60 cell differentiation' Biochem Biophys Res Commun 442, (1-2) 51-55 Author Site , DOI
Almzaiel AJ, Billington R, Smerdon G & Moody AJ 2013 'Effects of hyperbaric oxygen treatment on antimicrobial function and apoptosis of differentiated HL-60 (neutrophil-like) cells' Life Sci 93, (2-3) 125-131 Author Site , DOI
Al-Abady? ZN, Ferguson NS, John Moody A & Billington RA 2012 'CD38 expression regulates NAD(H) levels in human leukemia cells' Free Radical Biology and Medicine 53, S122-S123 , DOI
Conforti L, Wilbrey A, Morreale G, Janeckova L, Beirowski B, Adalbert R, Mazzola F, Di Stefano M, Hartley R & Babetto E 2009 'WldSprotein requires Nmnat activity and a short N-terminal sequence to protect axons in mice' The Journal of Cell Biology 184, (4) 491-500 , DOI
Gambara G, Billington RA, Debidda M, D'Alessio A, Palombi F, Ziparo E, Genazzani AA & Filippini A 2008 'NAADP-induced Ca2+ signaling in response to endothelin is via the receptor subtype B and requires the integrity of lipid rafts/caveolae' Journal of Cellular Physiology 216, (2) 396-404 , DOI
Galli U, Ercolano E, Carraro L, Blasi Roman CR, Sorba G, Canonico PL, Genazzani AA, Tron GC & Billington RA 2008 'Synthesis and biological evaluation of isosteric analogues of FK866, an inhibitor of NAD salvage' ChemMedChem 3, (5) 771-779 Author Site , DOI
Billington RA, Genazzani AA, Travelli C & Condorelli F 2008 'NAD depletion by FK866 induces autophagy' Autophagy 4, (3) 385-387 Author Site , DOI
Billington RA, Travelli C, Ercolano E, Galli U, Roman CB, Grolla AA, Canonico PL, Condorelli F & Genazzani AA 2008 'Characterization of NAD uptake in mammalian cells' J Biol Chem 283, (10) 6367-6374 Author Site , DOI
Genazzani AA & Billington RA 2008 '[Pharmacokinetic and pharmacodynamic features of palonosetron]' Tumori 94, (2) Author Site
Tron GC, Pirali T, Billington RA, Canonico PL, Sorba G & Genazzani AA 2008 'Click chemistry reactions in medicinal chemistry: applications of the 1,3-dipolar cycloaddition between azides and alkynes' Med Res Rev 28, (2) 278-308 Author Site , DOI
Deaglio S, Vaisitti T, Billington R, Bergui L, Omede' P, Genazzani AA & Malavasi F 2007 'CD38/CD19: a lipid raft–dependent signaling complex in human B cells' Blood 109, (12) 5390-5398 , DOI
Billington RA & Genazzani AA 2007 'PPADS is a reversible competitive antagonist of the NAADP receptor' Cell Calcium 41, (6) 505-511 Author Site , DOI
Pirali T, Gatti S, Di Brisco R, Tacchi S, Zaninetti R, Brunelli E, Massarotti A, Sorba G, Canonico PL & Moro L 2007 'Estrogenic analogues synthesized by click chemistry' ChemMedChem 2, (4) 437-440 Author Site , DOI
Billington RA, Bruzzone S, De Flora A, Genazzani AA, Koch-Nolte F, Ziegler M & Zocchi E 2006 'Emerging functions of extracellular pyridine nucleotides' Mol Med 12, (11-12) 324-327 Author Site , DOI
Billington RA, Harper C, Bellomo EA, Publicover S, Barratt CLR & Genazzani AA 2006 'Characterization of cyclic adenine dinucleotide phosphate ribose levels in human spermatozoa' Fertil Steril 86, (4) 891-898 Author Site , DOI
Moccia F, Billington RA & Santella L 2006 'Pharmacological characterization of NAADP-induced Ca2+ signals in starfish oocytes' BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 348, (2) 329-336 Author Site , DOI
Billington RA, Bellomo EA, Floriddia EM, Erriquez J, Distasi C & Genazzani AA 2006 'A transport mechanism for NAADP in a rat basophilic cell line' FASEB J 20, (3) 521-523 Author Site , DOI
Floriddia EM, Pace D, Genazzani AA, Canonico PL, Condorelli F & Billington RA 2005 'Sphingosine releases Ca2+ from intracellular stores via the ryanodine receptor in sea urchin egg homogenates' Biochem Biophys Res Commun 338, (3) 1316-1321 Author Site , DOI
Appendino G, Prosperini S, Valdivia C, Ballero M, Colombano G, Billington RA, Genazzani AA & Sterner O 2005 'SERCA-Inhibiting Activity of C-19 Terpenolides fromThapsiagarganicaand Their Possible Biogenesis' Journal of Natural Products 68, (8) 1213-1217 , DOI
Billington RA, Tron GC, Reichenbach S, Sorba G & Genazzani AA 2005 'Role of the nicotinic acid group in NAADP receptor selectivity' Cell Calcium 37, (1) 81-86 Author Site , DOI
Billington RA, Bak J, Martinez-Coscolla A, Debidda M & Genazzani AA 2004 'Triazine dyes are agonists of the NAADP receptor' Br J Pharmacol 142, (8) 1241-1246 Author Site , DOI
Billington RA, Thuring JW, Conway SJ, Packman L, Holmes AB & Genazzani AA 2004 'Production and characterization of reduced NAADP (nicotinic acid-adenine dinucleotide phosphate)' Biochem J 378, (Pt 1) 275-280 Author Site , DOI
Billington RA, Ho A & Genazzani AA 2002 'Nicotinic acid adenine dinucleotide phosphate (NAADP) is present at micromolar concentrations in sea urchin spermatozoa' J Physiol 544, (Pt 1) 107-112 Author Site , DOI
Billington RA, Ho A & Genazzani AA 2002 'Nicotinic acid adenine dinucleotide phosphate (NAADP) is present at micromolar concentrations in sea urchin spermatozoa' JOURNAL OF PHYSIOLOGY-LONDON 544, (1) 107-112 Author Site , DOI
Bak J, Billington RA & Genazzani AA 2002 'Effect of luminal and extravesicular Ca2+ on NAADP binding and release properties' Biochem Biophys Res Commun 295, (4) 806-811 Author Site , DOI
Genazzani AA & Billington RA 2002 'NAADP: an atypical Ca2+-release messenger?' Trends Pharmacol Sci 23, (4) 165-167 Author Site , DOI
Bak J, Billington RA, Timar G, Dutton AC & Genazzani AA 2001 'NAADP receptors are present and functional in the heart' Curr Biol 11, (12) 987-990 Author Site , DOI
Billington RA & Genazzani AA 2000 'Characterization of NAADP+ Binding in Sea Urchin Eggs' Biochemical and Biophysical Research Communications 276, (1) 112-116 , DOI
Reviews
Plattner H, Sehring IM, Mohamed IK, Miranda K, De Souza W, Billington RA, Genazzani AA & Ladenburger E-M 2012 'Calcium signaling in closely related protozoan groups (Alveolata): Non-parasitic ciliates (Paramecium, Tetrahymena) vs. parasitic Apicomplexa (Plasmodium, Toxoplasma)' Cell Calcium 51, 351-382
Chapters
Morgan AJ, Churchill GC, Masgrau R, Ruas M, Davis LC, Billington RA, Patel S, Yamasaki M, Thomas JM & Genazzani AA 2006 'Methods in Cyclic ADP-Ribose and NAADP Research' in Putney JW Calcium signaling CRC Press 265-334
Conference Papers
Al-Shabany A, Moody AJ, Foey AD & Billington RA 2014 'Pharmacological modulation of NAD alters TNF-alpha responses in macrophage subsets' 180-180 PEARL
Al-Shabany A, Moody J, Foey AD & Billington RA 2013 'NAD levels modulate macrophage subset responses' 92-92
Erriquez J, Bernascone S, Billington R, Grilli MG, Genazzani AA & Distasi C 2006 'Calcium signals induced by extracellular application of NAADP in developing neurons and glial cells' S10-S11
Billington RA, Bruzzone S, De Flora A, Genazzani AA, Koch-Nolte F, Ziegler M & Zocchi E 2006 'Emerging functions of extracellular pyridine nucleotides' 324-327 , DOI