Staff Profile

Roles and Responsibilities

As a research associate I am part of a team involved in work leading to improving the treatment of children with acute lymphoblastic leukaemia. We are looking for alternative therapies to decrease the amount of chemotherapeutic drugs children are given, and to decrease the toxicity of any drugs that have to be given. In addition we are working towards finding specific targeted drugs for individual patients with treatable genetic profiles.

Along with everyone else, I have to make sure that consumables are ordered so that experimental research work can continue without hindrance and all experimental results are written up and logged so that everyone in the group can understand and access them.

Within the NICR I am part of the paediatric research groups that have moved into a satellite research area based in the Herschel Building. I am the lab manager for this group of research workers and I am in charge of making sure the whole lab is in good running order. I liaise with everyone in the lab to sort out problems with broken equipment and I try to maintain the smooth day to day running of the lab.

Qualifications

B.Sc. in Agricultural Biochemistry and Nutrition

M.Sc. in Immunology

M.Sc. in Applied Bioinformatics

Previous Positions

Feb 2004-present Research Associate, NICR, Paul O'Gorman Building, University of Newcastle, Newcastle upon Tyne.

Oct 1997-Feb 2004 Research Associate, Paediatric Oncology Unit, Cancer Research Unit, University of Newcastle, Newcastle upon Tyne.

Oct 1995-Sept 1997 Research Associate, Department of Medical Molecular Biology (Pathology/Medicine), University of Newcastle, Newcastle upon Tyne.

Sept 1992-Sept 1995 Theartre Technician, Theatre Royal, Newcastle Playhouse, Live Theatre, Tyne Theatre and Opera House, all at Newcastle upon Tyne and The Maltings Art Centre, Berwick upon Tweed.

May 1988-Aug 1992 Research Technician, Department of Immunology, University of Newcastle, Newcastle upon Tyne.

Nov 1986-April 1988 Junior Research Associate, Department of Pathology, University of Newcastle, Newcastle upon Tyne.

June 1984-Oct 1986 Junior Research Associate, Department of Medicine, University of Newcastle, Newcastle upon Tyne.

July 1980-May 1984 Research Technician, Department of Medicine, University of Newcastle, Newcastle upon Tyne.

Oct 1978-June 1980 Research Technician, Department of Agricultural Biochemistry and Nutrition, University of Newcastle, Newcastle upon Tyne.

Memberships

British Association for Cancer Research

Languages

English
French (some)
BSL (some)

Research Interests

Analysing and sorting mononuclear cells from blood and bone marrow of patients with acute lymphocytic leukaemia using up to ten colour fluorescence on a Fisher Attune acoustic focusing flow cytometer, a FACSCanto, a FACSCalibur and a FACSAria machine.
Follow-up ten colour fluorescence analysis of bone marrow samples after the patient has started chemotherapy, to detect minimal residual disease.

Using an Amnis Image Stream cytometer to detect movement of molecules into and out of cells after specific treatments.

Analysis of  data after WGA and whole exome sequencing using my bioinformatics background.

Other Expertise

Long term cell culture using antibiotic free medium.
Isolation, fractionation and purification of blood and bone marrow mononulear cells using sucrose density centrifugation.
PCR, RQ-RT-PCR, immuno-PCR.
Isolation of DNA and RNA from pellets of mononulear cells.
Use of a Beckman CEQ 8000 for detecting LOH in sequential patient DNA samples using microsatellite markers.
FISH.
Immunocytochemistry, cryo-imunocytochemistry.
Protein detection using western SDS-PAGE analysis.
ELISA.
Isolation of viable mitrochondria fron cells and their subsequent analysis for changes in membrane potential/permeability and glutathione homeostasis.
Isolation of human thyroid and lymph node cells by mechanical disaggregation and enzyme digestion.
Stable and transient transfection of expression plasmids into mammalian cells in culture.
Generation, cloning and long term maintenance of mouse T lymphocyte clones.
Proliferation assays using 3H-Thymidine uptake and XTT (or MTT) colourimetric assays.
Antigen production and purification from plasmid infected E. coli using affinity chromatography and SDS-PAGE analysis.
Complement mediated cytotoxicity and antibody-dependent cell-mediated cytotoxicity using 51Cr labeled thyroid cell monolayers as target cells.
Labeling IgG, IgM, IgA and thyroglobulin with NaI125 for use in radio immunoassays.
Analysis of serum and urine for glucose, lipids, cholesterol, urea, a-amino acid nitrogen and insulin.
Analysis of faeces for protein, lipids, fibre and minerals.

Current Work

Analysis of patient blood and bone marrow using leukaemic cell CD markers. Sorting leukaemic cells from normal cells using FACS machines. Analysing follow-up samples for minimal residual leukaemic disease. Analysis of sequencing data.

Research Roles

I have responsibilities to look after the day to day running and maintenance of many of the machines in the lab, including the FACS machines, the RQ-RT-PCR machine and the spectrophotometer.
I am involved with day to day teaching and guiding of any student that works in our lab.

Funding

Mitochondrial permeability transition during spontaneous and steroid induced cell death in blasts from children with ALL, 1998 – 1999. £32,200. Hall, A.G., Kearns, P., Case, M.C. Leukaemia Research Fund.

A study of the cytotoxic effect of buthionine sulfoxamine in neuroblastoma, 1998 – 2000. £70,869. Hall, A.G., Case, M.C., Coulthard, S.A., Pearson, A.D.J. Neuroblastoma Society.

Mitochondrial glutathione homeostasis during drug-induced cell death in leukaemic cells, 2000 - 2003. £130,589. Hall, A.G., Case, M.C., McGuckin, A.G. North of England Children's Cancer Research Fund.

Undergraduate Teaching

Whenever students come into the lab for work experience or to carry out final year or MSc projects, I am always available to help with lab techniques and general queries about research and experimental work.

Postgraduate Teaching

Whenever post graduate students come into the lab, I am always available to help with lab techniques and general queries about research and experimental work.

• Vormoor B, Veal GJ, Griffin MJ, Boddy AV, Irving J, Minto L, Case M, Banerji U, Swales KE, Tall JR, Moore AS, Toguchi M, Acton G, Dyer K, Schwab C, Harrison CJ, Grainger JD, Lancaster D, Kearns P, Hargrave D, Vormoor J. A phase I/II trial of AT9283, a selective inhibitor of aurora kinase in children with relapsed or refractory acute leukemia: challenges to run early phase clinical trials for children with leukemia. Pediatric Blood & Cancer 2017, 64(6), e26351 1-4.
• Weiland J, Pal D, Case M, Irving J, Ponthan F, Koschmieder S, Heidenreich O, von Stackelberg A, Eckert C, Vormoor J, Elder A. BCP-ALL blasts are not dependent on CD19 expression for leukaemic maintenance. Leukemia 2016, 30(9), 1920–1923.
• Nicholson L, Evans C, Matheson E, Minto L, Keilty C, Sanichar M, Case M, Schwab C, Williamson D, Rainer J, Harrison C, Kofler R, Hall AG, Rednern CPF, Wheaton AD, Irving JAE. Quantitative proteomic analysis reveals maturation as a mechanism underlying glucocorticoid resistance in B lineage ALL and re-sensitization by JNK inhibition. British Journal of Haematology 2015, 171(4), 595–605.
• Irving J, Matheson E, Minto L, Blair H, Case M, Halsey C, Swidenbank I, Ponthan F, Kirschner-Schwabe R, Groeneveld-Krentz S, Hof J, Allan J, Harrison C, Vormoor J, von Stackelberg A, Eckert C. Ras pathway mutations are prevalent in relapsed childhood acute lymphoblastic leukemia and confer sensitivity to MEK inhibition. Blood. 2014;124(23):3420-3430. Blood 2015, 125(5), 890-890.
• Irving J, Matheson E, Minto L, Blair H, Case M, Halsey C, Swidenbank I, Ponthan F, Kirschner-Schwabe R, Groeneveld-Krentz S, Hof J, Allan J, Harrison C, Vormoor J, von Stackelberg A, Eckert C. Ras pathway mutations are prevalent in relapsed childhood acute lymphoblastic leukemia and confer sensitivity to MEK inhibition. Blood 2014, 124(23), 3420-3430.
• Nicholson L, Knight T, Matheson E, Minto L, Case M, Sanichar M, Bomken S, Vormoor J, Hall A, Irving J. Casitas B lymphoma mutations in childhood acute lymphoblastic leukemia. Genes, Chromosomes & Cancer 2012, 51(3), 250-256.
• Wilson K, Case MC, Minto L, Bailey S, Vormoor J, Irving JAE. The CD34⁺ CD38^Low CD19⁺ Candidate Leukemic Stem Cell Phenotype Revisited: Useful for Flow MRD Monitoring?. In: Blood: 50th Annual Meeting of the American Society of Hematology. 2008, San Francisco, California: American Society of Hematology.
• Wilson K, Rehe K, Bomken S, Case M, Shultz L, Irving J, Vormoor J. In Childhood ALL, Both Blasts with a CD20(-/Low) and a CD20(High) Immunophenotype, Have the Ability to Transfer the Leukemia Onto Immune-Deficient NOD/Scid Y-/- Mice. In: Blood: 50th Annual Meeting of the American Society of Hematology. 2008, San Francisco, California, USA: American Society of Hematology.
• Case M, Matheson E, Minto L, Hassan R, Harrison C, Bown N, Bailey S, Vormoor J, Hall A, Irving J. Somatic mutation of genes impacting on the RAS-RAF-MEK-ERK pathway is the most common genetic abnormality in childhood acute lymphoblastic leukaemia, is implicated in disease progression and provides a rationale for therapeutic targeting. In: British Journal of Haematology: 48th Annual Scientific Meeting of the British Society for Haematology. 2008, Glasgow, UK: Wiley-Blackwell Publishing Ltd.
• Moorman AV, Sulong S, Irving JAE, Strefford JC, Case MC, Minto CLJ, Harrison CJ, Hall AG. Inactivation of CDKN2A in childhood acute lymphoblastic leukaemia (ALL) occurs principally by deletion and is strongly correlated with cytogenetic subgroups. In: British Society of Haematology 48th Annual Scientific Meeting, incorporating the 6th Bi-Annual I-BFM Leukaemia Symposium. 2008, Glasgow, UK: Wiley-Blackwell Publishing Ltd.
• Sulong S, Moorman AV, Irving JAE, Strefford JC, Konn ZJ, Case MC, Minto L, Barber KE, Parker H, Wright SL, Stewart ARM, Bailey S, Bown NP, Hall AG, Harrison CJ. A comprehensive analysis of the CDKN2A gene in childhood acute lymphoblastic leukemia reveals genomic deletion, copy number neutral loss of heterozygosity, and association with specific cytogenetic subgroups. Blood 2009, 113(1), 100-107.
• Irving JAE, Jesson J, Virgo P, Case MC, Minto CLJ, Eyre L, Noel N, Johansson U, Macey M, Knotts L, Helliwell M, Davies P, Whitby L, Barnett D, Hancock J, Goulden N, Lawson S. Establishment and validation of a standard protocol for the detection of minimal residual disease in B lineage childhood acute lymphoblastic leukemia by flow cytometry in a multi-center setting. Haematologica 2009, 94(6), 870-874.
• Wilson K, Case M, Minto L, Bailey S, Bown N, Jesson J, Lawson S, Vormoor J, Irving J. Flow minimal residue disease monitoring of candidate leukemic stem cells defined by the immunophenotype, CD34⁺CD38^lowCD19⁺ in B-lineage childhoood acute lymphoblastic leukemia. Haematologica 2009, 95(4), 679-683.
• Case MC, Matheson E, Minto L, Hassan R, Harrison CJ, Bown NP, Bailey S, Vormoor J, Hall AG, Irving JAE. Mutation of genes affecting the RAS pathway is common in childhood acute lymphoblastic leukemia. Cancer Research 2008, 68(16), 6803-6809.
• Parker H, An Q, Barber K, Case MC, Davies TL, Konn Z, Stewart A, Wright S, Griffiths M, Ross FM, Moorman AV, Hall AG, Irving JAE, Harrison CJ, Strefford JC. The complex genomic profile of ETV6-RUNX1 positive acute lymphoblastic leukemia highlights a recurrent deletion of TBL1XR1. Genes, Chromosomes and Cancer 2008, 47(12), 1118-1125.
• Hogarth LA, Redfern CPF, Teodoridis J, Hall AG, Anderson HL, Case MC, Coulthard SA. The effect of thiopurine drugs on DNA methylation in relation to TPMT expression. Biochemical Pharmacology 2008, 76(8), 1024-1035.
• Matheson EC, Hogarth LA, Case MC, Irving JAE, Hall AG. DHFR and MSH3 co-amplification in childhood acute lymphoblastic leukaemia, in vitro and in vivo. Carcinogenesis 2007, 28(6), 1341-1346.
• Strefford J, Worley H, Barber KJ, Wright SL, Moorman AV, Case M, Irving J, Hall A, Harrison CJ. Genomic profiling reveals multiple genetic targets in ETV6-RUNX1 positive acute lymphoblastic leukaemia (ALL). In: British Human Genetics Conference. 2007, University of York, UK: Journal of Medical Genetics: BMJ Group.
• Moorman AV, Sulong S, Irving JAE, Strefford JC, Case MC, Minto L, Harrison CJ, Hall AG. Red blood cell alloimmunization is affected by depletion of donor white cell subsets. In: 49th Annual Meeting of the American Society of Hematology. 2007, Atlanta, Georgia: Blood: American Society of Hematology.
• Carr, J., Bown, N.P., Case, M.C., Hall, A.G., Lunec, J., Tweddle, D.A. High-resolution analysis of allelic imbalance in neuroblastoma cell lines by single nucleotide polymorphism arrays. Cancer Genetics and Cytogenetics 2007, 172(2), 127-138.
• Hall, A.G., Sulong, S., Harrison, C., Minto, C.L.J., Bown, N.P., Case, M.C., Bailey, S., Irving, J.A.E. Assessment of aneuploidy in childhood acute lymphoblastic leukaemia using high density oligonucleotide arrays. Blood 2006, 108(11).
• Sulong, S., Irving, J.A.E., Case, M.C., Minto, C.L.J., Bown, N., Bailey, S., Harrison, C., Hall, A.G. Comprehensive analysis of p16(INK4a) in childhood acute lymphoblastic leukemia reveals homozygous deletion, haploinsufficiency and acquired isodisomy at the 9p locus with intact p16(INK4a). Blood 2006, 108(11).
• Leslie M, Case MC, Hall AG, Coulthard SA. Expression levels of asparagine synthetase in blasts from children and adults with acute lymphoblastic leukaemia. British Journal of Haematology 2006, 132(6), 740-742.
• Irving, J.A.E., Minto, C.L.J., Matheson, E., Case, M.C., Bailey, S., Bown, N.P., Hassan, R., Harrison, C., Hall, A.G. Mutation in genes impacting on the RAS-RAF-MEK-ERK pathway are found at high incidence in childhood acute lymphoblastic leukemia at both diagnosis and at relapse. Blood 2006, 108(11), 160B-161B.
• Anderson RJ, Cairns D, Cardwell WA, Case MC, Groundwater PW, Hall AG, Hogarth LA, Jones AL, Meth-Cohn O, Suryadevara P, Tindall A, Thoene JG. Design, synthesis and initial in vitro evaluation of novel prodrugs for the treatment of cystinosis. Letters in Drug Design & Discovery 2006, 3(5), 336-345.
• Irving JAE, Bloodworth LC, Bown NP, Case MC, Hogarth LA, Hall AG. Loss of heterozygosity in childhood acute lymphoblastic leukemia detected by genome-wide microarray single nucleotide polymorphism analysis. Cancer Research 2005, 65(8), 3053-3058.
• Sulong, S., Case, M.C., Minto, C.L.J., Wilkins, B., Hall, A.G., Irving, J. The V617F mutation in Jak2 is not found in childhood acute lymphoblastic leukaemia. British Journal of Haematology 2005, 130(6), 964-965.
• Leslie M, Case MC, Hall AG, Coulthard SA. Potential use of asparagine synthetase levels in the individualisation of L-asparaginase therapy. In: British Cancer Research Meeting. 2003, Bournemouth, UK: British Journal of Cancer: Nature Publishing Group.
• Leslie M, Case MC, Hall AG, Coulthard SA. Measurement of aspargine synthetase mRNA levels by real-time PCR. British Journal of Cancer 2001, 85(supplement 1), 60.
• Case MC, Hall AG. Glutathione homeostasis in buthionine sulfoximine sensitive and resistant neuroblastoma cell lines. British Journal of Cancer 2000, 83(Supplement 1), 64 P143.
• Case MC, Burt AD, Hughes J, Palmer JM, Collier JD, Bassendine MF, Yeaman SJ, Hughes MA, Major GN. Enhanced ultrasensitive detection of structurally diverse antigens using a single immuno-PCR assay protocol. Journal of Immunological Methods 1999, 223(1), 93-106.
• Major GN, Notarianni GB, Ross SJ, Case MC, Brannigan JA, Roper DI, Potter PM, Brent TP, Moody PCE. Evidence for autoproteolysis of substrate-inactivated O-6-methylguanine-DNA methyltransferase following DNA repair. In: British Journal of Cancer. 1999, Nature Publishing Group.
• Case MC, Burt AD, Hughes J, Palmer JM, Collier JD, Bassendine MF, Yeaman SJ, Hughes MA, Major GN. Erratum to 'Enhanced ultrasensitive detection of structurally diverse antigens using a single immuno-PCR assay protocol' (Journal of Immunological Methods (1999) 223 (93-106)). Journal of Immunological Methods 1999, 226(1-2), 189-190.
• Case MC, Major GN, Bassendine MF, Burt AD. The universality of immuno-PCR for ultrasensitive antigen detection. Biochemical Society Transactions 1997, 25(2), S374-S374.
• Case MC, Major GN, Bassendine MF, Burt AD. The universality of immuno-PCR for ultrasensitive antigen detection. Immunology 1996, 89(Suppl.1), OH394-OH394.