Background

Flow Cytometry Core Facility Manager

High Dimensional Cytometry Specialist 

I am a high dimensional cytometry specialist and mass cytometry specialist within the flow cytometry core facility. My principal responsibilities are to support genomic, mass and high-parameter fluorescence cytometry projects: providing in-depth panel advice, project planning and expertise for our high-end analysers and cytof systems.

As a UK expert in high-plex cytometry, I lead the Newcastle University Single Cell Technologies special interest group within the Innovation, Methodology and Application theme. We continue to ensure that Newcastle University remains at the global forefront of single cell analysis and that our data is of the highest quality and reproducibility.

Previous Appointments

Post-doctoral Research Associate: Primary Immunodeficiency.

Investigating the genetic and molecular basis of novel, human, primary immune deficiencies. 

Qualifications

PhD: Autoimmune Endocrinology

Investigating the immunomodulatory effects of antithyroid drugs in autoimmune thyroid disease via structurally induced changes in autoantigens.

Research

Research Interests

Genomic Cytometry

I have a special interest in the combinatorial analysis of protein and RNA using targeted sequencing approaches at he single cell level. The flow cytometry core facility at Newcastle University is at the forefront of these genomic cytometry assays utilising BD Rhapsody technology to investigate multiple disease states affecting our UK population.  

Imaging Mass Cytometry and Cytof Analysis

As one of the most experienced imaging and suspension mass cytometry operators in Europe, I work with our highly skilled team to ensure that we consistently drive this critical resource within the FCCF to its full potential. With a crucial focus on optimising methodology we ensure the data from our system is robust and of the vey highest standard.

High Dimensional Fluorescence Cytometry

As an early adopter of high-plex fluorescent cytometry, I continue to push the achievable boundaries of fluorescent cytometry. Our efforts to optimise panel design and implementation has realised the full potential of our 30 parameter Symphony A5 analyser. As the flow cytometry core moves to advancements in spectra cytometry, we will once again be increasing the measurable parameter space in this exciting field.  

Primary immunodeficiency

By way of whole-exome deep-sequencing followed by molecular characterisation, my post-doctoral research aimed to unravel the underlying basis of novel, human, primary immune deficiencies. I continue to identify as an immunologist as well as a cytometrist with a particular interested in lymphocyte signalling, senescence and cell-death pathways.

Viral recognition and killing by natural killer cells

Previous research also sort to understand NK-cell immune evasion strategies employed by Herpes viruses, a common complication in immunocompromised individuals

Publications

• Articles

  • Musgrave KM, Scott J, Sendama W, Gardner AI, Dewar F, Lake CJ, Spronk HMH, van Oerle R, Visser M, ten Cate H, Kesteven P, Fuller A, McDonald D, Knill C, Hulme G, Filby A, Wright SE, Roy AI, Ruchaud-Sparagano M, Simpson AJ, Rostron AJ. Tissue factor expression in monocyte subsets during human immunothrombosis, endotoxemia and sepsis. Thrombosis Research 2023, 228, 10-20.
  • Lim JX, Lai CY, Mallett GE, McDonald D, Hulme G, Laba S, Shapanis A, Payne M, Patterson W, Alexander M, Coxhead J, Filby A, Plummer R, Lovat PE, Sciume G, Healy E, Amarnath S. Programmed cell death-1 receptor-mediated regulation of Tbet⁺NK1.1^- innate lymphoid cells within the tumor microenvironment. Proceedings of the National Academy of Sciences of the United States of America 2023, 120(18), e2216587120.
  • Chen C, McDonald D, Blain A, Mossman E, Atkin K, Marusich MF, Capaldi R, Bone L, Smith A, Filby A, Erskine D, Russell O, Hudson G, Vincent AE, Reeve AK. Parkinson’s disease neurons exhibit alterations in mitochondrial quality control proteins. npj Parkinson's Disease 2023, 9, 120.
  • Hunter B, Nicorescu I, Foster E, McDonald D, Hulme G, Fuller A, Thomson A, Goldsborough T, Hilkens CMU, Majo J, Milross L, Fisher A, Bankhead P, Wills J, Rees P, Filby A, Merces G. OPTIMAL: An OPTimized Imaging Mass cytometry AnaLysis framework for benchmarking segmentation and data exploration. Cytometry Part A 2024, 105(1), 36-53.
  • Masic D, Fee K, Bell H, Case M, Witherington G, Lansbury S, Ojeda-Garcia J, McDonald D, Schwab C, Van Delft FW, Filby A, Irving JAE. Hyperactive CREB subpopulations increase during therapy in pediatric B-lineage acute lymphoblastic leukemia. Haematologica 2023, 108(4), 981-992.
  • Ajaib S, Lodha D, Pollock S, Hemmings G, Finetti MA, Gusnanto A, Chakrabarty A, Ismail A, Wilson E, Varn FS, Hunter B, Filby A, Brockman AA, McDonald D, Verhaak RGW, Ihrie RA, Stead LF. GBMdeconvoluteR accurately infers proportions of neoplastic and immune cell populations from bulk glioblastoma transcriptomics data. Neuro-Oncology 2023, 25(7), 1236-1248.
  • Hipps D, Dobson PF, Warren C, McDonald D, Fuller A, Filby A, Bulmer D, Laude A, Russell O, Deehan DJ, Turnbull DM, Lawless C. Detecting respiratory chain defects in osteoblasts from osteoarthritic patients using imaging mass cytometry. Bone 2022, 158, 116371.
  • Leslie J, Mackey JBG, Jamieson T, Ramon-Gil E, Drake TM, Fercoq F, Clark W, Gilroy K, Hedley A, Nixon C, Luli S, Laszczewska M, Pinyol R, Esteban-Fabro R, Willoughby CE, Haber PK, Andreu-Oller C, Rahbari M, Fan C, Pfister D, Raman S, Wilson N, Muller M, Collins A, Geh D, Fuller A, Mcdonald D, Hulme G, Filby A, Cortes-Lavaud X, Mohamed N-E, Ford CA, Raffo Iraolagoitia XL, Mcfarlane AJ, Mccain MV, Ridgway RA, Roberts EW, Barry ST, Graham GJ, Heikenwalder M, Reeves HL, Llovet JM, Carlin LM, Bird TG, Sansom OJ, Mann DA. CXCR2 inhibition enables NASH-HCC immunotherapy. Gut 2022, Epub ahead of print.
  • Chen C, Mossman E, Malko P, McDonald D, Blain AP, Bone L, Erskine D, Filby A, Vincent AE, Hudson G, Reeve AK. Astrocytic Changes in Mitochondrial Oxidative Phosphorylation Protein Levels in Parkinson's Disease. Movement Disorders 2022, 37(2), 302-314.
  • Chen C, McDonald D, Blain A, Sachdeva A, Bone L, Smith ALM, Warren C, Pickett SJ, Hudson G, Filby A, Vincent AE, Turnbull DM, Reeve AK. Imaging mass cytometry reveals generalised deficiency in OXPHOS complexes in Parkinson’s disease. npj Parkinson's Disease 2021, 7(1), 39.
  • Reynolds G, Vegh P, Fletcher J, Poyner EFM, Stephenson E, Goh I, Botting RA, Huang N, Olabi B, Dubois A, Dixon D, Green K, Maunder D, Engelbert J, Efremova M, Polański K, Jardine L, Jones C, Ness T, Horsfall D, McGrath J, Carey C, Popescu D-M, Webb S, Wang X-N, Sayer B, Park J-E, Negri VA, Belokhvostova D, Lynch MD, McDonald D, Filby A, Hagai T, Meyer KB, Husain A, Coxhead J, Vento-Tormo R, Behjati S, Lisgo S, Villani A-C, Bacardit J, Jones PH, O'Toole EA, Ogg GS, Rajan N, Reynolds NJ, Teichmann SA, Watt FM, Haniffa M. Developmental cell programs are co-opted in inflammatory skin disease. Science 2021, 371(6527), eaba6500.
  • Jardine L, Webb S, Goh I, Quiroga Londono M, Reynolds G, Mather M, Olabi B, Stephenson E, Botting RA, Horsfall D, Engelbert J, Maunder D, Mende N, Murnane C, Dann E, McGrath J, King H, Kucinski I, Queen R, Carey CD, Shrubsole C, Poyner E, Acres M, Jones C, Ness T, Coulthard R, Elliott N, O'Byrne S, Haltalli MLR, Lawrence JE, Lisgo S, Balogh P, Meyer KB, Prigmore E, Ambridge K, Jain MS, Efremova M, Pickard K, Creasey T, Bacardit J, Henderson D, Coxhead J, Filby A, Hussain R, Dixon D, McDonald D, Popescu D-M, Kowalczyk MS, Li B, Ashenberg O, Tabaka M, Dionne D, Tickle TL, Slyper M, Rozenblatt-Rosen O, Regev A, Behjati S, Laurenti E, Wilson NK, Roy A, Gottgens B, Roberts I, Teichmann SA, Haniffa M. Blood and immune development in human fetal bone marrow and Down syndrome. Nature 2021, 598, 327-331.
  • Warren C, McDonald D, Capaldi R, Deehan D, Taylor RW, Filby A, Turnbull DM, Lawless C, Vincent AE. Decoding mitochondrial heterogeneity in single muscle fibres by imaging mass cytometry. Scientific Reports 2020, 10(1), 15336.
  • Jardine L, Wiscombe S, Reynolds G, McDonald D, Fuller A, Green K, Filby A, Forrest I, Ruchaud-Sparagano MH, Scott J, Collin M, Haniffa M, Simpson AJ. Lipopolysaccharide inhalation recruits monocytes and dendritic cell subsets to the alveolar airspace. Nature Communications 2019, 10, 1999.
  • Zhang Z, Gothe F, Pennamen P, James JR, McDonald D, Mata CP, Modis Y, Alazami AM, Acres M, Haller W, Bowen C, Doffinger R, Sinclair J, Brothers S, Zhang Y, Matthews H, Naudion S, Pelluard F, Alajlan H, Yamazaki Y, Notarangelo LD, Thaventhiran JED, Engelhardt KR, Al-Mousa H, Hambleton S, Rooryck C, Smith KGC, Lenardo MJ. Human interleukin-2 receptor β mutations associated with defects in immunity and peripheral tolerance. Journal of Experimental Medicine 2019, 216(6), 1311-1327.
  • Popescu DM, Botting RA, Stephenson E, Green K, Webb S, Jardine L, Calderbank EF, Polanski K, Goh I, Efremova M, Acres M, Maunder D, Vegh P, Gitton Y, Park JE, Vento-Tormo R, Miao Z, Dixon D, Rowell R, McDonald D, Fletcher J, Poyner E, Reynolds G, Mather M, Moldovan C, Mamanova L, Greig F, Young MD, Meyer KB, Lisgo S, Bacardit J, Fuller A, Millar B, Innes B, Lindsay S, Stubbington MJT, Kowalczyk MS, Li B, Ashenberg O, Tabaka M, Dionne D, Tickle TL, Slyper M, Rozenblatt-Rosen O, Filby A, Carey P, Villani AC, Roy A, Regev A, Chédotal A, Roberts I, Göttgens B, Behjati S, Laurenti E, Teichmann SA, Haniffa M. Decoding human fetal liver haematopoiesis. Nature 2019, 574, 365–371.
  • Reis M, McDonald D, Nicholson L, Godthardt K, Knobel S, Dickinson AM, Filby A, Wang X-N. Global phenotypic characterisation of human platelet lysate expanded MSCs by high-throughput flow cytometry. Scientific Reports 2018, 8(1), 3907.
  • Villani A-C, Satija R, Reynolds G, Sarkizova S, Shekhar K, Fletcher J, Griesbeck M, Butler A, Zheng S, Lazo S, Jardine L, Dixon D, Stephenson E, Nilsson E, Grundberg I, McDonald D, Filby A, Li W, De Jager PL, Rozenblatt-Rosen O, Lane AA, Haniffa M, Regev A, Hacohen N. Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors. Science 2017, 356(6335), eaah4573.
  • Lu W, Zhang Y, McDonald DO, Jing HE, Carroll B, Robertson N, Zhang Q, Griffin H, Sanderson S, Lakey JH, Morgan NV, Reynard LN, Zheng L, Murdock HM, Turvey SE, Hackett SJ, Prestidge T, Hall JM, Cant AJ, Matthews HF, Koref MFS, Simon AK, Korolchuk VI, Lenardo MJ, Hambleton S, Su HC. Dual Proteolytic Pathways Govern Glycolysis and Immune Competence. Cell 2014, 159(7), 1578-1590.
  • Dickinson RE, Griffin H, Bigley V, Reynard LN, Hussain R, Haniffa M, Lakey JH, Rahman T, Wang XN, McGovern N, Pagan S, Cookson S, McDonald D, Chua I, Wallis J, Cant A, Wright M, Keavney B, Chinnery PF, Loughlin J, Hambleton S, Santibanez-Koref M, Collin M. Exome sequencing identifies GATA-2 mutation as the cause of dendritic cell, monocyte, B and NK lymphoid deficiency. Blood 2011, 118(10), 2656-2658.
  • McDonald DO, Pearce SHS. Thyroid peroxidase forms thionamide-sensitive homodimers: relevance for immunomodulation of thyroid autoimmunity. Journal of Molecular Medicine 2009, 87(10), 971-980.
  • Roycroft M, Fichna M, McDonald D, Owen K, Zurawek M, Gryczynska M, Januszkiewicz-Lewandowska D, Fichna P, Cordell H , Donaldson P, Nowak J, Pearce S. The tryptophan 620 allele of the lymphoid tyrosine phosphatase (PTPN22 gene) predisposes to autoimmune Addison's disease. Clinical Endocrinology 2009, 70(3), 358-362.
  • Skinningsrud B, Husebye ES, Pearce SH, McDonald DO, Brandal K, Wolff AB, Lovas K, Egeland T, Undlien DE. Polymorphisms in CLEC16A and CIITA at 16p13 are associated with primary adrenal insufficiency. Journal of Clinical Endocrinology and Metabolism 2008, 93(9), 3310-3317.

• Conference Proceedings (inc. Abstracts)

  • Griffin H, McDonald DO, Singh-Dang T, Dickinson R, Grainger A, Reynard L, Hussain R, Cant AJ, Gennery AR, Abinun M, Flood TJ, Collin MP, Loughlin J, Morgan NV, Santibanez-Koref M, Hambleton S. Whole exome sequencing as a diagnostic tool in primary immunodeficiency. In: 15th Biennial Meeting European Society for Immunodeficiency (ESID). 2012, Florence, Italy: Springer.
  • Hambleton S, McDonald DO, Morgan NV, Griffin H, Singh-Dang T, Grainger A, Reynard L, Gennery AR, Slatter M, Flood TJ, McKiernan P, Barge D, Abinun M, Hackett S, Loughlin J, Lakey J, Cant AJ, Santibanez-Koref M. Autosomal recessive combines immunodeficiency due to loss of function mutation in Tripeptidyl Peptidase II. In: 15th Biennial Meeting European Society for Immunodeficiency (ESID). 2012, Florence, Italy: Springer.
  • McDonald D, Morgan N, Griffin H, Dang TS, Grainger A, Reynard L, Loughlin J, Santibanez-Koref M, Hambleton S. Whole-exome deep sequencing identifies a novel causative mutation in primary immunodeficiency. In: Immunology: Annual Congress of the British Society for Immunology. 2011, Liverpool, UK: Wiley-Blackwell Publishing Ltd.
  • Morgan NV, Goddard S, Cardno TS, Rahman F, Crupek A, Straatman-Iwanowska A, Pasha S, Hambleton S, Cant A, Barge D, Gennery A, McDonald D, Anderson G, Huissoon A, Tate WP, Maher ER. A novel human immunodeficiency disorder associated with a mutation in the T cell receptor a subunit constant gene (TRAC). In: Clinical and Experimental Immunology: United Kingdom Primary Immunodeficiency Network Immunology Forum. 2010, Bath, UK: British Society for Immunology.