The University of Sheffield
Department of Human Metabolism

Dr Lynne Lennard BSc PhD

Reader in PharmacologyLynne Lennard

Academic Unit of Clinical Pharmacology
Department of Human Metabolism
Floor E
The Medical School
Beech Hill Road
Sheffield
S10 2RX

Tel: +44 (0) 114 2712759
Email: l.lennard@sheffield.ac.uk

Biography

I gained my PhD in biochemistry in 1978 and became interested in biochemical pharmacology and the variability in human drug metabolism. As a postdoctoral research fellow my research group was funded by the Medical Research Council, the Yorkshire Cancer Research Campaign and the Leukaemia Research Fund. I gained a Lectureship at the University of Sheffield in 1995 becoming a Senior Lecturer in 1999 and a Reader in Pharmacology shortly thereafter.

Research Interests

My current research is based around the role of pharmacogenetics in the clinical response to anti-cancer drugs. Maximal efficacy of anticancer treatment is of prime importance because of the potential repercussions in cancer patients, particularly those with drug responsive cancers such as childhood acute lymphoblastic leukaemia (ALL).

Working within national therapeutic trials for ALL my aim is to maximise the therapeutic response to antimetabolite chemotherapy, a long-term phase of continuing treatment which is given to maintain leukaemia remission. These studies involve the identification of children "resistant" and "sensitive" to thiopurine drugs prior to the start of chemotherapy and the influence of the thiopurine methyltransferase genetic polymorphism on the response to subsequent treatment. Similarly, studies in methotrexate metabolism seek to show whether variations in active metabolite formation influence treatment outcome.

Methodologies applied to the study the mode of action of antimetabolite drugs as anti-cancer agents have been extended to study the mechanisms involved when these compounds are used as immunosuppressive agents in the treatment of inflammatory bowel disease, autoimmune hepatitis and rheumatoid arthritis.

Current projects

• The role of mercaptopurine pharmacogenetics in the response to maintenance chemotherapy in children with acute lymphoblastic leukaemia (ALL).
• Thiopurine studies within the UK clinical trials for childhood ALL. Thiopurine-response genes and the outcome of therapy.
• The role of thiopurine dose intensity and treatment outcome in ALL protocols.
• Azathioprine pharmacogenetics in autoimmune hepatitis: relationship to toxicity and to therapeutic efficacy.
• Azathioprine pharmacogenetics in inflammatory bowel disease.

Teaching interests

I am actively involved in both undergraduate and postgraduate teaching and assessment. My teaching interests are chemotherapy, immunosuppression, drugs and haematological dysfunction and drug metabolism. I contribute to the research Student Selected Component of the MBChB course and BMedSci attachments for medical undergraduates.

Professional activities

Editorial Board of Therapeutic Drug Monitoring.

Key publications

  1. Hinchliffe RF, Bellamy GJ, Finn A , Vora AJ, Lennard L. Reference intervals for red cell variables and platelet counts in infants at 2,5 and 13 months of age: a cohort study. J Clin Pathol 2013, in press. Published online 13.07.13 doi:10.1136/jclinpath-2013-201742
  2. Hinchliffe RF, Bellamy GJ, Finn A , Vora AJ, Lennard L. Utility of red cell distribution width in screening for iron deficiency. Arch Dis Child 2013;98:545-547. doi:10.1136/archdischild-2012-303160
  3. Lennard L, Cartwright CS, Wade R, Richards SM, Vora A. Thiopurine methyltransferase genotype-phenotype discordance, and thiopurine active metabolite formation, in childhood acute lymphoblastic leukaemia. British Journal of Clinical Pharmacology, 2013;76:125-136. doi: 10.1111/bcp.12066
  4. Appell ML, Berg J, Duley J, Evans WE, Kennedy MA, Lennard L, Marinaki T, McLeod HL, Relling MV, Schaeffeler E, Schwab M, Weinshilboum R, Yeoh AEJ, McDonagh EM, Hebert JM, Klein TE, Coulthard SA. Nomenclature for alleles of the thiopurine methyltransferase (TPMT) gene. Pharmacogenetics and Genomics. 2013;23(4):242-248. doi: 10.1097/FPC.0b013e32835f1cc0
  5. Dhaliwal HK, Anderson R, Thornhill EL, Schneider S, McFarlane E, Gleeson D, Lennard L. Clinical significance of azathioprine metabolites for the maintenance of remission in autoimmune hepatitis. Hepatology 2012;56:1401-1408. DOI: 10.1002/hep.25760
  6. Mooney PD, Sanders DS, Hadjivassilou M, Lennard L. Commentary: Tioguanine in the treatment of refractory coeliac disease. Aliment Pharmacol Ther, 2012;36:594-596
  7. Lennard L. Methyltransferases. In: Biotransformation (Ed FP Guengerich), Comprehensive Toxicology.Elsevier, Oxford, U.K. 2010, Vol 4, Chapter 21
  8. Lennard L, Richards S, Cartwright CS, Mitchell C, Lilleyman JS, Vora A. The thiopurine methyltransferase genetic polymorphism is associated with thioguanine-related veno-occlusive disease of the liver in children with acute lymphoblastic leukaemia. Clin Pharm Ther 2006; 80: 375-383
  9. Vora AJ, Mitchell CD, Lennard L, Eden OB, Kinsey SE, Lilleyman JS, Richards S. Toxicity and efficacy of thioguanine compared with mercaptopurine in childhood lymphoblastic leukaemia: Results of the UK Medical Research Council Randomised Trial ALL97. Lancet 2006; 368: 1339-1348
  10. Wright S, Sanders D, Lobo AJ, Lennard L. The clinical significance of azathioprine active metabolite concentrations in inflammatory bowel disease. Gut, 2004; 53: 1123-1128
  11. Lennard L, Rees CA, Lilleyman JS, Maddocks JL. Highly-cited paper republished as a citation classic in acknowledgement of novelty and impact in the field of cancer therapy. Childhood leukaemia: a relationship between intracellular 6-mercaptopurine metabolites and neutropenia. Br J Clin Pharmacol 1983; 16:359-363. Republished in: Br J Clin Pharmacol 2004; 58:S867-S874
  12. Lennard L, Lilleyman JS, Van Loon JA, Weinshilboum RM. Highly-cited paper republished as a citation classic in acknowledgement of novelty and impact in the field of cancer therapy. Genetic variation in response to 6-mercaptopurine for childhood acute lymphoblastic leukaemia. The Lancet 1990; 336:225-229. Republished in: Esteve Foundation Series, No 5. Pharmacology revisited, Eds Evans WE and Relling MV. Prous Science Press, Barcelona, 2003 pages 71-75