How does platelet stimulation by a variety of agonists lead to activation and platelet aggregation? We are interested in elucidating the signalling pathways that are involved in platelet activation, in particular those that may play a role in platelet hyperactivity in conditions such as obesity and diabetes. Platelets are able to respond to a wide range of agonists and when activated at the site of injury they rapidly aggregate to form a platelet haemostatic plug. Increased or inappropriate platelet activation, however, will lead to thrombosis and vascular complications. Risk factors such as obesity and some genetic factors lead to a resistance to insulin, which is the major underlying cause of type II, adult-onset diabetes, the most common type of diabetes. Type II diabetes is associated with an increased risk of cardiovascular complications, which is the main cause of morbidity and mortality in these patients. There is substantial evidence for platelet hyperactivity in patients with diabetes, which is thought to play a contributory role in diabetic heart disease. Although, the pathogenesis of diabetic cardiovascular disease is not yet fully understood, it is likely to involve the clustering of certain risk factors, often called the insulin resistance syndrome, which is associated with type II diabetes. In our lab, we are interested in investigating the contribution of these risk factors to making platelets hyper responsive.
Durrant TN, van den Bosch MT, Hers I.
Blood. 2017 Aug 9. pii: blood-2017-03-773614. doi: 10.1182/blood-2017-03-773614. [Epub ahead of print]

Temporal contribution of the platelet body and balloon to thrombin generation.

Agbani EO, Hers I, Poole AW.

Haematologica. 2017 Jul 13. pii: haematol.2017.166819. 


Agbani EO, Williams CM, Hers I and Poole AW. 
Sci Reports. 2017 Jun 5;7(1):2770.

Durrant TN, Hutchinson JL, Heesom KJ, Anderson KE, Stephens LR, Hawkins PT, Marshall AJ, Moore SF and Hers I.
Blood Adv. 2017; 1:918-932

Battram AM, Durrant TN, Agbani EO, Heesom KJ, Paul DS, Piatt R, Poole AW, Cullen PJ, Bergmeier W, Moore SF, Hers I.

J Biol Chem. 2017 Feb 3;292(5):1691-1704.  


Identification of roles for the SNARE-associated protein, SNAP29, in mouse platelets.

Williams CM, Savage JS, Harper MT, Moore SF, Hers I, Poole AW.

Platelets. 2016 Jun;27(4):286-94. 


Coordinated Membrane Ballooning and Procoagulant Spreading in Human Platelets. 

Agbani EO, van den Bosch MT, Brown E, Williams CM, Mattheij NJ, Cosemans JM, Collins PW, Heemskerk JW, Hers I, Poole AW.

Circulation. 2015 Oct 13;132(15):1414-24. 

 

Blair TA, Moore SF, Hers I.

J Thromb Haemost. 2015 Aug;13(8):1479-93.


Loss of the insulin receptor in murine megakaryocytes/platelets causes thrombocytosis and alterations in IGF signalling.

Moore SF, Williams CM, Brown E, Blair TA, Harper MT, Coward RJ, Poole AW, Hers I.

Cardiovasc Res. 2015 Jul 1;107(1):9-19.


Platelet dense granule secretion defects may obscure α-granule secretion mechanisms: evidence from Munc13-4-deficient platelets.

Harper MT, van den Bosch MT, Hers I, Poole AW. 

Blood. 2015 May 7;125(19):3034-6. 


Hers I, Poole AW.
Blood. 2014 Aug 14;124(7):992-3.

Blair TA, Moore SF, Williams CM, Poole AW, Vanhaesebroeck B, Hers I
Arterioscler Thromb Vasc Biol 2014; first published on June 5 2014

PKC and P2Y12 take centre stage in thrombin-mediated activation of mTORC1 in human platelets.

Moore SF, Hunter RW, Hers I.

J Thromb Haemost 2014; 12:748-60.

















PREVIOUS LAB MEMBERS





INGEBORG HERS
Principal Investigator
Reader in Pharmacology and Cell Signalling
i.hers@bristol.ac.uk
Publications





SAMANTHA MOORE

Senior Research Associate

Samantha.Moore@bristol.ac.uk

Publications






ROGER HUNTER

Senior Research Associate

roger.hunter@bristol.ac.uk







TOM DURRANT

Research Associate

tom.durrant@bristol.ac.uk

Publications





KAMILA SLEDZ

PhD student














NINA SMITH

MSc student











THOMAS BLAIR

PhD Student

tom.blair@bristol.ac.uk

Publications






ANTHONY BATTRAM
PhD Student

anthony.battram@bristol.ac.uk

Ingeborg graduated from the VU University Amsterdam with a degree in Medical Biology. She obtained her PhD at the University of Utrecht in the lab of Professors Jan-Willem Akkerman and Jan Sixma in 1998 with a thesis entitled 'Regulation of platelet integrin alphaIIbbeta3'. She subsequently worked as a postdoctoral researcher in the lab of Prof Steve Watson in the Department of Pharmacology at the University of Oxford, before moving to the lab of Profs Dick Denton and Jeremy Tavare in the Department of Biochemistry at the University of Bristol. In 2004, she obtained a British Heart Foundation Intermediate Research Fellowship, which allowed her to establish her own research group. She moved her lab in 2010 to the School of Physiology, Pharmacology and Neuroscience and was promoted to Reader in Pharmacology and Cell Signaling in 2015.









Samantha graduated from King’s College London with a degree in pharmacology with toxicology. As part of her degree she undertook a 12 month sandwich placement at the James Black Foundation. She then obtained her PhD from the University of Bath in Amanda Mackenzie’s lab in 2009, with her thesis entitled “The role of fast ATP-gated P2X receptors in inflammation”. 
Samantha obtained a Wellcome Trust VIP Award to extend her research, before joining the Hers lab in 2009 as a British Heart Foundation-funded post-doctoral researcher.





Roger graduated from the University of Bristol with a 1st class degree in Biochemistry and subsequently obtained his PhD from the University of Bristol in the lab of Ingeborg Hers in 2009, with his thesis entitled: 'Investigations into the role of Protein Kinase B in human platelets'. He then moved to the lab of Kei Sakamoto at the MRC phosphorylation Unit Dundee as a postdoctoral research associate and a year later joined Kei Sakamoto in his move to Nestle, Lausanne in Switzerland. Roger returned to Bristol in July 2016 and presently works in the Hers lab as a British Heart Foundation-funded senior postdoctoral researcher.    






Tom graduated from King’s College London with a degree in pharmacology, including a 12 month placement within the Neuropharmacology Team at GlaxoSmithKline.  He then obtained his PhD from the University of Cambridge, investigating Class IA PI3K signalling specificity under the supervision of Phillip Hawkins FRS and Len Stephens FRS, at the Babraham Institute.  Tom joined the Hers lab in 2013 as a British Heart Foundation-funded post-doctoral researcher.






Kamila graduated from the University of Bedfordshire with a degree in Biomedical Science. She then obtained her MSc in Transfusion and Transplantation Science from the University of Bristol, and soon after she started working as a Senior Research Assistant at the Antigen Engineering Department (NHS Blood and Transplant / Bristol Institute for Transfusion Sciences). Meanwhile she completed her HCPC/BMS registration portfolio at the Histocompatibility & Immunogenetics laboratory (NHSBT) and later moved to the Stem Cell & Immunotherapies department, where she worked as a Specialist Biomedical Scientist. Kamila joined the Hers lab in October 2016 as a British Heart Foundation-funded PhD student.
















Nina graduated from the University of Bristol in 2016 with a 1st class degree in Pharmacology. She started her MSc by Research in the Hers lab in October 2016 studying the mechanisms by which thrombopoietin potentiates platelet function and submitted her thesis in July 2017 and is now studying medicine at the University of Birmingham.















Tom graduated from Liverpool John Moore’s University in 2012 with a 1st class degree in Medical Biochemistry. Prior to commencing his studies Tom worked as a quality control laboratory assistant for a clinical nutrition company called Vitaflo International Ltd (part of the Nestle Health Science Division). He joined the lab in October 2012 as a BHF funded PhD student and graduated in January 2016. Tom presently works as a postdoctoral research fellow in Prof Alan Michelson's lab (Harvard Medical School, Boston, USA).












Anthony graduated from Imperial College London in 2012 with a 1st class degree in Biochemistry with a Year in Industry/Research. During his third year, he carried out a 12 month industrial placement at GlaxoSmithKline (Stevenage) working in the DN
A Sequencing group. Anthony joined the lab in October 2012 as a BHF funded PhD student and graduated in July 2016. He presently works as a postdoctoral research associate for Prof. Doreen Cantrell at the University of Dundee.
Co-supervised group members: Marion van den Bosch (Alastair Poole's Group)
Previous group members:  Roger Hunter (BHF-funded PhD student 2005-2009), Lawrence Hutchinson (Post-doctoral researcher 2013-2015), Anthony Battram (BHF-funded PhD student 2012-2015), Thomas Blair (BHF-funded PhD student 2012-2015), Marion van den Bosch (ERASMUS MSc student 2010).