Professor Catrin Pritchard

Professor Pritchard’s research is focussed on the use of two different preclinical cancer models for drug and biomarker discovery; tumour explants and genetically engineered mouse models.

The group have optimised conditions for the ex vivo culture of fragments of human tumours as patient derived explants (PDEs) without the requirement for tumour deconstruction. PDEs have the advantage over other preclinical models in that tumour architecture is retained intact, making them amenable to the testing of agents that target the tumour microenvironment including immune checkpoint inhibitors. The group works with commercial organisations and translational charities to test the efficacy of novel anti-cancer agents in development and are applying digital pathology solutions at endpoint to identify and validate predictive and pharmacodynamic biomarkers. Their approach is being applied to a wide range of human primary and metastatic cancers including breast, colorectal, lung, endometrial, renal cancers as well as melanoma and mesothelioma.

The group uses genetically engineered mouse models to better understand mechanisms of tumour development driven by oncogenic BRAF and RAS. Most of their work has focussed on using these models as tools for understanding the contribution of the tumour microenvironment to tumour initiation and progression, with an emphasis on lung adenocarcinoma and colorectal cancer development. Their work has unravelled novel secreted factors that play key roles in regulating cell-cell interactions in the tumour microenvironment and an impact of cholesterol metabolism on tumour associated macrophage function.

Since 2015

• Kamata T, Al Dujaily E, Alhamad S, So TY, Margaritaki O, Giblett S, Pringle JH, Le Quesne J, Pritchard C (2021) Statins mediate anti- and pro-tumourigenic functions in lung adenocarcinoma development by remodelling the tumour microenvironment. Disease, Models and Mechanisms DOI: 10.1242/dmm.049148.
• Harber J, Kamata T, Pritchard C, Fennell D (2021) Matter of TIME: the tumor-immune microenvironment of mesothelioma and its implications for checkpoint blockade efficacy. Journal for ImmunoTherapy of Cancer. DOI: 10.1136/jitc-2021-003032.
• Viticchie G, Powley I, Demetriou C, Cooper J, Butterworth M, Patel M, Abid N, Miles G, Howells L, Pringle H, MacFarlane M, Pritchard C (2021) Patient-derived tumour explants as a “live” preclinical platform for predicting drug resistance in patients. Journal of Visualised Experiments.DOI: 10.3791/62130
• Maeda Y, Tidyman WE, Ander BP, Pritchard CA, Rauen KA (2021) RAS/MAPK Dysregulation in development causes a skeletal myopathy in an activating BrafL597V mouse model for Cardio-facio-cutaneous syndrome. Dev Dynamics DOI: 10.1002/dvdy.309
• Crezee T, Tesselaar M, Nagarajah J, Corver W, Morreau J, Pritchard C, Kimura S, Kuiper J, van Engen-van Grusven I, Smit J, Metea-Maier R, Plantinga T (2021) Digoxin treatment reactivates in vivo thyroid-specific radioactive iodide uptake and correlates with favorable clinical outcome in non-meduallary thyroid cancer. Cellular Oncology 10.1007/s13402-021-00588-y
• Collins A, Miles GJ, Powley IR, Hew R, Pringle JH, MacFarlane M, Pritchard C, Moss EL (2020) Development of a patient-derived explant model for prediction of drug responses in endometrial cancer. Gynaecology Oncology DOI: 10.1016/j.ygyno.2020.11.033
• Collins A, Miles G, Wood J, MacFarlane M, Pritchard C, Moss E (2020) Patient-derived explants, xenografts and organoids: 3-dimensional patient-relevant pre-clinical models in endometrial cancer. Gynaecology Oncology. 156: 251-259.
• Zhang M, Sun QQ, Harber J, Dawson A, Luo J-L, Nakas A, Busacca S, Sharkey A, Waller D, Sheaff MT, Richards C, Wells-Jordan P, Gaba A, Poille C, Baitei EY, Bzura A, Dzialo J, Jama M, Le Quesne J, Bajaj A, Martinson L, Shaw J, Pritchard C, Kamata T, Kuse N, Brannan L, Zhang P, Yang H, Griffiths G, Wilson G, Swanton C, Dudbridge F, Hollox EJ, Fennell DA (2020) Clonal architecture in mesothelioma is prognostic and shapes the tumour microenvironment. Nature Communications 12: 1751.
• Miles GJ, Powley I, Mohammed S, Howells L, Pringle H, Hammonds T, MacFarlane M, Pritchard C (2020). Evaluating and comparing immunostaining and computational methods for spatial profiling of drug response in patient-derived explants. Laboratory Investigation. 101: 396-407.
• Kamata T, So TY, Ahmed Q, Giblett S, Patel B, Luo J, Reddel R, Pritchard, C (2020) Fibroblast-derived STC-1 modulates tumour associated macrophages and lung adenocarcinoma development. Cell Reports 31: 107802.
• Powley IR, Patel M, Miles G, Pringle H, Howells L, Thomas A, Kettleborough K, Bryans J, Hammonds T, MacFarlane M, Pritchard C (2020) Patient-Derived Explants (PDEs) as a powerful preclinical platform for anti-cancer drug and biomarker discovery. British Journal of Cancer 122: 735-744. DOI: 10.1038/s41416-019-0672-6.
• Greenhalgh C, Karekla E, Miles G, Powley I, Pritchard C, MacFarlane M, Pringle JH, Managh A (2020) Exploration of matrix effects in laser ablation inductively coupled plasma mass spectrometry imaging of cisplatin-treated tumours. Analytical Chemistry 92: 9847-9855.
• MacKenzie D, Robertson N, Rather I, Reid C, Sendzikaite G, Cruickshanks H, McBryan T, Pritchard C, Blyth K, Adams PD (2020) DNMT3B has oncogenic activity but evidence suggests that it does not promote CIMP nor cooperate with activated BRAFV600E in human intestinal cancer. iScience 23: 100838.
• Al Dujaily E, Baena J, Das M, Sereno M, Smith C, Kamata T, Officer L, Pritchard C, Le Quesne J (2019) Statin use is associated with decreased pro-tumourigenic macrophages within in situ but not invasive regions of human lung adenocarcinomas. JNCI Cancer Spectrum 4: pkz101.
• Rakhit CP, Trigg RM, Le Quesne J, Kelly M, Shaw JA, Pritchard C, Martins LM (2019) Early detection of premalignant lesions in a KRAS^G12D-driven mouse lung cancer model by monitoring circulating free DNA. Disease Models and Mechanisms. 2019 Feb 12;12(2). pii: dmm036863. doi: 10.1242/dmm.036863.
• Hey F, Andreadi C, Noble C, Patel B, Jin H, Kamata T, Straatman K, Luo J, Balmanno K, Jones DTW, Collins VP, Cook SJ, Caunt CJ, Pritchard C (2018) Over-expressed, N-terminally truncated BRAF is detected in the nucleus of cells with nuclear phosphorylated MEK and ERK. Heliyon 4: e01065.
• Adamo P, Cowley CM, Neal CP, Mistry V, Page K, Dennison A, Isherwood J, Hastings R, Luo J, Martins LM, Pritchard C, Manson M, Shaw J (2017) Profiling tumour heterogeneity through circulating tumour DNA in patients with Pancreatic Cancer. Oncotarget 8: 87221-87233.
• Kamata T, Giblett S, Pritchard C (2017) KRAS^G12D expression in lung-resident myeloid cells promotes pulmonary LCH-like neoplasm sensitive to statin treatment. Blood 130: 514-526.
• Zou M, Baitei EY, BinEssa H, Al-Mohanna FA, Parhar RS, St-Arnaud R, Kimura S, Pritchard C, Alzahrani AS, Assiri AM, Meyer BF, Shi Y (2017) Cyp24a1 attenuation limits progression of BrafV600E-induced papillary thyroid cancer cells and sensitizes them to BrafV600E inhibitor PLX4720. Cancer Research 77: 2161-2172.
• Papaioannou G, Petit ET, Liu ES, Baccarini M, Pritchard C, Demay MB (2017) Raf Kinases are Essential for Phosphate Induction of Erk1/2 Phosphorylation in Hypertrophic Chondrocytes and Normal Endochondral Bone Development. Journal of Biological Chemistry 292: 3164-3171.
• Karekla E, Liao W-J, Sharpe B, Pugh J, Le Quesne J, Moore D, Pritchard C*, MacFarlane M*, Pringle JH (2017) Ex-vivo explant culture of NSCLC provides a relevant pre-clinical model for evaluation of primary tumour responses to anti-cancer therapies. Cancer Research 77: 2029-2039. *Co-corresponding authors.
• Cammareri P, Rose AM, Vincent DF, Wang J, Nagano A, Libertini S, Ridgway RA, Athineos D, Coates PJ, McHugh A, Pourreyron C, Dayal JH, Larsson J, Weidlich S, Spender LC, Sapkota GP, Purdie KJ, Proby CM, Harwood CA, Leigh IM, Clevers H, Barker N, Karlsson S, Pritchard C, Marais R, Chelala C, South AP, Sansom OJ, Inman GJ (2016) Inactivation of TGFb receptors in stem cells drives cutaneous squamous cell carcinoma. Nature Communications 7: 12493.
• Zou M, Baitei EY, Al-Rijjal RA, Parhar RS, Al-Mohanna FA, Kimura S, Pritchard C, Binessa HA, Alzahrani AS, Al-Khalaf HH, Hawwari A, Akhtar M, Assiri AM, Meyer BF, Shi Y (2015) Thyroid stimulating hormone overcomes BrafV600E-induced senescence to promote tumor progression via down-regulation of p53 expression in papillary thyroid cancer. Oncogene 35: 1909-1918.
• Hey F, Giblett S, Forrest S, Herbert C, Pritchard C (2016) Phosphorylations of serines 21/9 in Glycogen Synthase Kinase 3b are not required for lineage commitment or WNT signaling in the normal mouse intestine. Plos One 11: e0156877.
• Aguilar Hernandez M, Patel B, Hey F, Giblett S, Davis H, Pritchard C (2016) Regulation of BRAF protein stability by a negative feedback loop involving the MEK-ERK pathway but not the FBXW7 tumour suppressor. Cell Signalling 28: 561-571.
• Kamata T, Jin H, Giblett S, Patel B, Patel F, Foster C, Pritchard C (2015) The cholesterol binding protein NPC2 restrains recruitment of stromal macrophage-lineage cells to early-stage mouse lung tumours. EMBO Molecular Medicine 7: 1119-1137.
• Lenos K, Goos JACM, Vuist IM, den Uil SJ, Delis-van Dieman PM, Belt EJT, Stockmann HBAC, Bril H, de Wit M, Carvalho B, Giblett S, Pritchard CA, Meijer GA, van Kooyk Y, Fijneman RJA, van Vliet SJ (2015) MGL-ligand expression is correlated to BRAF mutation and associated with poor survival of stage III colorectal cancer patients. OncoTarget 6: 26278-26290.
• Zou M, Baitei EY, Al-Rijjal RA, Parhar RS, Al-Mohanna FA, Kimura S, Pritchard C, BinEssa H, Alanazi AA, Alzahrani AS, Akhtar M, Assiri AM, Meyer BF, Shi Y (2015) KRASG12D mediated oncogenic transformation of thyroid follicular cells requires long-term TSH stimulation and is regulated by SPRY1. Lab Invest 95: 1269-1277.

Link to personal Pubmed profile https://pubmed.ncbi.nlm.nih.gov/?term=Pritchard+C+Leicester

• MSc Cancer Molecular Pathology and Therapeutics 
• BSX300 – Third year projects
• BS3003 – Cancer Cell and Molecular Biology
• BS2092 – Molecular Cell Biology

• Preclinical cancer models
• Tumour explants
• Drug and biomarker discovery