Staff Profile

Roles and Responsibilities

My responsibilities are to develop novel lines of research aimed at identifying genes involved in the development or relapse of leukaemia.

Qualifications

1982; BSc. in Applied Biology, Class 2[II], University of Bradford.
1984; Postgraduate Diploma in Genetic Toxicology, University of Swansea.
2002; PhD. in Haematology, University College London.

Areas of expertise

Genomic and functional characterisation of childhood leukaemia

Previous Positions

1984 -1986: Study Investigator with Microtest Research Ltd, University of York, UK
1986 -1989: Basic Grade Cytogeneticist, Regional Cytogenetics Unit, St Mary's Hospital, Manchester.
1989 -1991: Research Training Fellow, Department of Medical Genetics, St Mary's Hospital, Manchester
1993: English Teacher, English American College, Malaga, Spain.
1994-1998: Clinical Scientist, Department of Haematology, Addenbrooke's Hospital, Cambridge.
1999-2004: Research Assistant, Academic Department of Haematology, Royal Free and University Hospital School of Medicine, London
2004-2008: Research Associate, Department of Cell and developmental Biology, University of Illinois, Urbana, USA.

Languages

Intermediate Spanish

Research Interests

Main areas of expertise are cytogenetics and molecular genetics, cell biology and analysis of nuclear structure. Main research interests are the genetics of human leukaemia and changes in higher order chromatin structure associated with differentiation of embryonic stem cells.

Current Work

1. Analysis of a breakpoint cluster region associated with intrachromal amplification of chrmosome 21 in paediatric-pre-B cell leukaemia.
2. Development of a high-throughput in-vivo assay for the identification of candidate oncogenes and tumour suppressor genes in Leukaemia.

Future Research

Analysis of candidte oncogenes and tumour suppressor genes from chromosomal regions that are recurrently lost or gained or mutated in haematological malignancies using in-vivo models of leukaemia.

Research Roles

My current research roles are 1) the analysis and interpretation of sequences of breakpoints of chromosomal abnormalities in Leukaemia.
2) The introduction of novel in-vivo assays for the identification of novel oncogenes and tumour suppressor genes.

Postgraduate Supervision

None currenty. I will have responsibility for the supervision of a PhD student to commence within the next 18 months.

Funding

I played a major role in the preparation of two successful grant applications. 1) A Tyneside Research Asociation grant. To fund myself as a postdoctoral RA for 18 months.
2) An ERC advanced grant. To fund a 5 year research program aimed at introducing in-vivo models for the identification of novel genes contributin to leukaemia.

• Sinclair PB, Blair HH, Ryan SL, Buechler L, Cheng J, Clayton J, Hanna R, Hollern S, Hawking Z, Bashton M, Schwab CJ, Jones L, Russell LJ, Marr H, Carey P, Halsey C, Heidenreich O, Moorman AV, Harrison CJ. Dynamic clonal progression in xenografts of acute lymphoblastic leukemia with intrachromosomal amplification of chromosome 21. Haematologica 2018, 103, 634-644.
• Dixon ZA, Nicholson L, Zeppetzauer M, Matheson E, Sinclair P, Harrison CJ, Irving JAE. CREBBP knockdown enhances RAS/RAF/MEK/ERK signaling in Ras pathway mutated acute lymphoblastic leukemia but does not modulate chemotherapeutic response. Haematologica 2017, 102(4), 736-745.
• Williams MT, Yousafzai YM, Elder A, Rehe K, Bomken S, Frishman-Levy L, Tavor S, Sinclair P, Dormon K, Masic D, Perry T, Weston VJ, Kearns P, Blair H, Russell LJ, Heidenreich O, Irving JA, Izraeli S, Vormoor J, Graham GJ, Halsey C. The ability to cross the blood-cerebrospinal fluid barrier is a generic property of acute lymphoblastic leukemia blasts. Blood 2016, 127(16), 1998-2006.
• Ryan SL, Matheson E, Grossmann V, Sinclair P, Bashton M, Schwab C, Towers W, Partington M, Elliott A, Minto L, Richardson S, Rahman T, Keavney B, Skinner R, Bown N, Haferlach T, Vandenberghe P, Haferlach C, Santibanez-Koref M, Moorman AV, Kohlmann A, Irving JA, Harrison CJ. The role of the RAS pathway in iAMP21-ALL. Leukemia 2016, 30, 1824-1831.
• Sinclair P, Cheng J, Raninga P, Hanna R, Hollern S, Enshaei A, Blair H, Nakjang S, Ryan S, Eswaran J, Buechler L, Heidenreich O, Harrison C. A Targeted Functional Clone Tracking Assay for the Identification of Tumour Suppressor Genes in BCP- ALL Implicates the Transcription Factors FOXO3 and PRDM1. In: 57th American Society of Hematology (ASH) Annual Meeting. 2015, Orlando, FL, USA: American Society of Hematology.
• Yousafzai YM, Williams MTS, Bhatti S, Cousins A, Rehe K, Bomken S, Sinclair P, Weston VJ, Russell LJ, Heidenreich O, Irving JAE, Vormoor J, Graham GJ, Halsey C. Childhood pre-B acute lymphoblastic leukaemia cells capable of central nervous system engraftment are common, heterogeneous and transit the blood-cerebrospinal fluid barrier. In: 55th Annual Scientific Meeting of the British Society for Haematology. 2015, Edinburgh, UK: Wiley.
• Eswaran J, Sinclair P, Heidenreich O, Irving J, Russell LJ, Hall A, Calado DP, Harrison CJ, Vormoor J. The pre-B-cell receptor checkpoint in acute lymphoblastic leukaemia. Leukemia 2015, 29(8), 1623-1631.
• Li Y, Schwab C, Ryan SL, Papaemmanuil E, Robinson HM, Jacobs P, Moorman AV, Dyer S, Borrow J, Griffiths M, Heerema NA, Carroll AJ, Talley P, Bown N, Telford N, Ross FM, Gaunt L, McNally RJ, Young BD, Sinclair P, Rand V, Teixeira MR, Joseph O, Robinson B, Maddison M, Dastugue N, Vandenberghe P, Haferlach C, Stephens PJ, Cheng J, Van-Loo P, Stratton MR, Campbell PJ, Harrison CJ. Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemia. Nature 2014, 508(7494), 98-102.
• Eswaran J, Sinclair P, Nakjang S, Harrison CJ. Identification of Cmtm Family Proteins As Tumor Suppressor and Membrane Regulator in B Cell Precursor Acute Lymphoblastic Leukemia. In: 56th ASH Annual Meeting and Exposition. 2014, San Francisco: American Society of Hematology.
• Clayton J, Cheng J, Ryan S, Harrison CJ, Sinclair P. Oncogenomic Screening Strategies to Identify Tumour Suppressor Genes on Chromosome 12 in Acute Myeloid Leukaemia. In: 56th ASH Annual Meeting and Exposition. 2014, San Francisco, CA: American Society of Hematology.
• Sinclair PB, Parker H, An Q, Rand V, Ensor H, Harrison CJ, Strefford JC. Analysis of a breakpoint cluster reveals insight into the mechanism of intrachromosomal amplification in a lymphoid malignancy. Human Molecular Genetics 2011, 20(13), 2591-2602.
• Rand V, Parker H, Russell LJ, Schwab C, Ensor H, Irving J, Jones L, Masic D, Minto L, Morrison H, Ryan S, Robinson H, Sinclair P, Moorman A, Strefford J, Harrison CJ. Genomic characterization implicates iAMP21 as a likely primary genetic event in childhood B-cell precursor acute lymphoblastic leukemia. Blood 2011, 117(25), 6848-6855.
• Sinclair PB, Bian Q, Plutz M, Heard E, Belmont AS. Dynamic plasticity of large -scale chromatin structure revealed by self-assembly of engineered chromosome regions. Journal of Cell Biology 2010, 190(5), 761-776.
• Belmont AS, Hu Y, Sinclair PB, Wu W, Bian Q, Kireev I. Insights into interphase large-scale chromatin structure from analysis of engineered chromosome regions. Cold Spring Harbor Symposia on Quantitative Biology 2010, 75, 453-460.
• Rego A, Sinclair PB, Tao W, Kireev I, Bemont AS. The facultative heterochromatin of the inactive X chromosome has a distinctive condensed ultrastructure. Journal of Cell Science 2008, 121(7), 1119-1127.
• Sinclair PB, Harrison CJ, Jarosova M, Foroni L. Analysis of balanced rearrangements of chromosome 6 in acute leukemia: clustered breakpoints in q22-q23 and possible involvement of c-MYB in a new recurrent translocation, t(6;7)(q23;q32 through 36). Haematologica 2005, 90(5), 602-611.
• Sinclair PB, Sorour A, Martineau M, Harrison CJ, Mitchell WA, O'Neill E, Foroni L. A fluorescence in situ hybridization map of 6q deletions in acute lymphocytic leukemia: identification and analysis of a candidate tumor suppressor gene. Cancer Research 2004, 64(12), 4089-4098.
• Sohal J, Chase A, Mould S, Corcoran M, Oscier D, Iqbal S, Parker-Welborn J, Harris RI, Martinelli G, Montefusco V, Sinclair P, Wilkins BS, van den Berg H, Vanstraelen D, Goldman JM, Cross NC. Identification of four new translocations involving FGFR1 in myeloid disorders. Genes, Chromosomes and Cancer 2001, 32(2), 155-163.
• Vieira SA, Deininger MW, Sourour A, Sinclair P, Foroni L, Goldman JM, Melo JV. Transcription factor BACH2 is transcriptionally regulated by the BCR/ABL oncogene. Genes, Chromosomes and Cancer 2001, 32(4), 353-363.
• Jackson A, Carrara P, Duke V, Sinclair PB, Papaioannou M, Harrison CJ, Foroni L. Deletion of 6q16-q21 in human lymphoid maligancies: a mapping and deletion analysis. Cancer Research 2000, 60(11), 2775-2779.
• Sinclair PB, Nacheva EP, Leversha M, Telford N, Chang J, Reid A, Bench A, Champion K, Huntley B, Green AR. Large deletions at the t(9;22) breakpoint are common and may define a poor-prognosis subgroup of patients with chronicmyeloid leukemia. Blood 2000, 95(3), 738-744.
• Gribble S, Sinclair PB, Grace C, Green AR, Nacheva EP. Comparative analysis of G-banding, chromosome painting, locus specific FISH and CGH in chronic myeloid leukemia blast chrisis. Cancer Genetics and Cytogenetics 1999, 111(1), 7-17.
• Rahman SL, Mahendra P, Nacheva E, Sinclair P, Arno J, Marcus RE. Achievement of complete cytogenetic remission after two very low-dose doner leucocyte infusions in a patient with extensive cGVHD relapsing in accelerated phase post allogeneic BMT for CML. Bone Marrow Transplantation 1998, 21(9), 955-956.
• Sinclair PB, Green AR, Grace C, Nacheva EP. Improved sensitivity of BCR-ABL detection: a triple-probe three colour fluorescence in situ hybridisation system. Blood 1997, 90(4), 1395-1402.
• Mahendra P, Richards EM, Sinclair P, Nacheva E, Marcus RE. t(9;13)(q34;q12) chromosomal translocation persisting 4 years post autologous bone marrow transplantation for secondary AML despite morphological remission. Clinical and Laboratory Haematology 1996, 18(2), 121-122.
• Reeve A, Norman P, Sinclair P, Whittington-Smith R, Hamey Y, Donnai D, Read A. A true telomeric translocation in a baby with Prader-Willi phenotype. American Journal of Medical Genetics 1993, 47, 1-6.
• McKinley M, Colley A, Sinclair P, Donnai D, Andrews T. Denovo ring chromosome 3: a new case with a mild phenotype. Journal of Medical Genetics 1991, 28(8), 536-538.
• Sinclair PB, Ryan S, Bashton M, Hollern S, Hanna R, Case M, Schwalbe EC, Schwab CJ, Cranston RE, Young BD, Irving JAE, Vora AJ, Moorman AV, Harrison CJ. SH2B3 inactivation through CN-LOH-12q is uniquely associated with B-cell precursor ALL with iAMP21 or other chromosome 21 gain. Leukemia 2019, 33, 1881-1894.
• Cranston RE, Sinclair PB, Bashton M, Selby MP, Harrison CJ. A Genome-Wide CRISPR Screen Implicates MYC Dysregulation in TCF3-PBX1 B-ALL. In: 60th ASH Annual Meeting. 2018, San Diego, CA, USA: American Society of Hematology.