Role
Please visit my lab website for more information.
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 would-be Biologist with particular interests in birds, mammals (terrestrial and marine), reptiles, medicinal plants and a number of intvertebrate 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.
Qualifications & background
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.
Publications
Selected Publications
2008
Galli U, Ercolano E, Carraro L, Blasi Roman CR, Sorba G, Canonico PL, Genazzani AA, Tron GC, Billington RA. Synthesis and Biological Evaluation of Isosteric Analogues of FK866, an Inhibitor of NAD Salvage. ChemMedChem. (2008) 3(5);771-9
Billington RA, Genazzani AA, Travelli C, Condorelli F. NAD depletion by FK866 induces autophagy. Autophagy. (2008) 4(3):385-7.
Billington RA, Travelli C, Ercolano E, Galli U, Roman CB, Grolla AA, Canonico PL, Condorelli F, Genazzani AA. Characterization of NAD uptake in mammalian cells. J Biol Chem. (2008) 283(10), 6367-74.
Tron GC, Pirali T, Billington RA, Canonico PL, Sorba G, Genazzani A, Click chemistry reactions in medicinal chemistry: Applications of the 1,3-dipolar cycloaddition between azides and alkynes. Med Res Rev (2008) 28(2), 278-308.
2007
Deaglio S, Vaisitti T, Billington RA, Bergui L, Omede' P, Genazzani AA, Malavasi F. CD38/CD19: a lipid raft-dependent signaling complex in human B cells. Blood. (2007) 109(12), 5390-8.
Billington RA, Genazzani AA. PPADS is a reversible competitive antagonist of the NAADP receptor. Cell Calcium (2007) 41(6), 505-511.
2006
Billington RA, Bellomo EA, Floriddia EM, Erriquez J, Distasi C, Genazzani AA. A transport mechanism for NAADP in a rat basophilic cell line. Faseb J. (2006) 20 (3), 521-3.
Billington RA, Bruzzone S, De Flora A, Genazzani AA, Koch-Nolte F, Ziegler M, Zocchi E. Emerging functions of extracellular pyridine nucleotides. Mol. Med. (2006) 12(11-12), 324-7.
2004
Billington RA, Thuring JW, Conway SJ, Packman L, Holmes AB, Genazzani AA. Production and characterization of reduced NAADP (nicotinic acid-adenine dinucleotide phosphate). Biochem J. 2004 378:275-80.
2002
Billington RA, Ho A, Genazzani AA. Nicotinic acid adenine dinucleotide phosphate (NAADP) is present at micromolar concentrations in sea urchin spermatozoa. J Physiol. 2002 544:107-12.
2001
Bak J, Billington RA, Timar G, Dutton AC, Genazzani AA. NAADP receptors are present and functional in the heart. Curr Biol. 2001 11(12):987-90.
