Member Listing

Name

DaveMSmith

Title

Dr

Research Summary

Summary
• 30 years postdoctoral experience in ‘research-only’ academic and industry positions and have gained a wide range of pharmacology and biochemistry skills.
• 19 years experience in drug discovery from project level bioscience up to strategic and portfolio management. Involved mainly in identification of new targets but have also worked in lead optimisation projects to find candidate drugs, clinical trials and post marketing life cycle management.
• I have specialist knowledge of diabetes, obesity and particularly islet biology.

Current role – Principal Scientist – AZ Open Innovation, Cambridge UK (2015 onwards)
I manage a portfolio of around 50 collaborations with academic groups with the aim of taking a new target idea, setting up a primary screening assay and progressing it to find the first chemical equity. In these Target Innovation collaborations AstraZeneca supplies small molecule compound libraries for screening, drug discovery expertise and for some projects performs the primary HTS and secondary screens in house. The projects are mainly set in the core AZ areas of oncology, cardiovascular and metabolic and respiratory but we also contribute greatly to the neuroscience area.

My role is to manage the overall portfolio. This involves finding and reviewing potential new targets, progressing to a research agreement and then project managing the collaboration to its end point which is usually either the first chemical lead series or if it is a phenotypic screen to identify novel targets. Here my previous academic experience is critical in understanding the difficulties of obtaining grant funding as is my pharma experience in progressing early translational projects. The eventual aim here is to either bring projects into AZ or to spin them out with VC funding. In the course of these collaborations I have set up not only collaborations with individual universities but also with academic drug discovery units such as LifeArc (UK), LDC (Germany), Kaertor Foundation (Spain) and CDRD (Canada). These are particularly interesting vehicles for project progression as they have translational funding already set aside and can move more quickly than the grant funding route.

Expertise

Endocrinology, Regenerative Medicine

Selected Publications

Last 10 publications:
1. Abadpour S, Tyrberg B, Schive SW, Huldt CW, Gennemark P, Ryberg E, Rydén-Bergsten T, Smith DM, Korsgren O, Skrtic S, Scholz H, Winzell MS. Inhibition of the prostaglandin D2-GPR44/DP2 axis improves human islet survival and function. Diabetologia. 2020 Apr 29. doi: 10.1007/s00125-020-05138-z.

2. Hendrikse ER, Liew LP, Bower RL, Bonnet M, Jamaluddin MA, Prodan N, Richards KD, Walker CS, Pairaudeau G, Smith DM, Rujan RM, Sudra R, Reynolds CA, Booe JM, Pioszak AA, Flanagan JU, Hay MP, Hay DL. Identification of Small-Molecule Positive Modulators of Calcitonin-like Receptor-Based Receptors. ACS Pharmacol Transl Sci. 2020 Mar 12;3(2):305-320. doi: 10.1021/acsptsci.9b00108. eCollection 2020 Apr 10

3. Brito H, Marques V, Afonso MB, Brown DG, Börjesson U, Selmi N, Smith DM, Roberts IO, Fitzek M, Aniceto N, Guedes RC, Moreira R, Rodrigues CMP. Phenotypic high-throughput screening platform identifies novel chemotypes for necroptosis inhibition. Cell Death Discov. 2020 Feb 11;6:6. doi: 10.1038/s41420-020-0240-0. eCollection 2020.

4. Pollard AE, Martins L, Muckett PJ, Khadayate S, Bornot A, Clausen M, Admyre T, Bjursell M, Fiadeiro R, Wilson L, Whilding C, Kotiadis VN, Duchen MR, Sutton D, Penfold L, Sardini A, Bohlooly-Y M, Smith DM, Read JA, Snowden MA, Woods A, Carling D. AMPK activation protects against diet induced obesity through Ucp1-independent thermogenesis in subcutaneous white adipose tissue.
Nat Metab. 2019 Mar;1(3):340-349. doi: 10.1038/s42255-019-0036-9. Epub 2019 Feb 25

5. Eyre HJ, Speight T, Glazier JD, Smith DM, Ashton N.
Urotensin II in the development and progression of chronic kidney disease following ⅚ nephrectomy in the rat.
Exp Physiol. 2019 Mar;104(3):421-433. doi: 10.1113/EP087366. Epub 2019 Jan 15

6. Kishore M, Cheung KCP, Fu H, Bonacina F, Wang G, Coe D, Ward EJ, Colamatteo A, Jangani M, Baragetti A, Matarese G, Smith DM, Haas R, Mauro C, Wraith DC, Okkenhaug K, Catapano AL, De Rosa V, Norata GD, Marelli-Berg FM.
Regulatory T Cell Migration Is Dependent on Glucokinase-Mediated Glycolysis.
Immunity. 2018 Apr 17;48(4):831-832. doi: 10.1016/j.immuni.2018.03.034. No abstract available.

7. Martinez-Sanchez A, Nguyen-Tu MS, Cebola I, Yavari A, Marchetti P, Piemonti L, de Koning E, Shapiro AMJ, Johnson P, Sakamoto K, Smith DM, Leclerc I, Ashrafian H, Ferrer J, Rutter GA.
MiR-184 expression is regulated by AMPK in pancreatic islets.
FASEB J. 2018 May;32(5):2587-2600. doi: 10.1096/fj.201701100R. Epub 2018 Jan 8.
PMID:29269398

8. Moodaley R, Smith DM, Tough IR, Schindler M, Cox HM.
Agonism of free fatty acid receptors 1 and 4 generates peptide YY-mediated inhibitory responses in mouse colon.
Br J Pharmacol. 2017 Dec;174(23):4508-4522. doi: 10.1111/bph.14054. Epub 2017 Nov 8.
PMID:28971469
9. Trevaskis JL, Sacramento CB, Jouihan H, Ali S, Le Lay J, Oldham S, Bhagroo N, Boland BB, Cann J, Chang Y, O’Day T, Howard V, Reers C, Winzell MS, Smith DM, Feigh M, Barkholt P, Schreiter K, Austen M, Andag U, Thompson S, Jermutus L, Coghlan MP, Grimsby J, Dohrmann C, Rhodes CJ, Rondinone CM, Sharma A. Neurturin and a GLP-1 Analogue Act Synergistically to Alleviate Diabetes in Zucker Diabetic Fatty Rats. Diabetes 2017 Jul;66(7):2007-2018. doi: 10.2337/db16-0916

10. Kristinsson H, Sargsyan E, Manell H, Smith DM, Göpel SO, Bergsten P. Basal hypersecretion of glucagon and insulin from palmitate-exposed human islets depends on FFAR1 but not decreased somatostatin secretion. Sci Rep. 2017 Jul 5;7(1):4657. doi: 10.1038/s41598-017-04730-5