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University of Exeter Medical School

Dr Pia Leete

Dr Pia Leete

Senior Research/ RD Lawrence Fellow

 P.Leete@exeter.ac.uk

 RILD Building 4.06

 

University of Exeter Medical School, RILD Building, RD&E Hospital Wonford, Barrack Road, Exeter, EX2 5DW, UK


Overview

My research group focusses on exploring the immunopathology of Type 1 diabetes in the pancreas.

After a nontraditional career trajectory, I am a current and proud recipient of a Diabetes UK RD Lawrence Fellowship, and also a fierce advocate for the notion that "anything is possible".

My observations have led to the proposal that two distinct forms of Type 1 diabetes (T1D) exist, and that age at diagnosis is a strongly prognostic factor which form a person has. One form, or "endotype", is most often diagnosed in early life (<10y), and is linked to an aggressive loss of beta-cells by the time of diagnosis. Conversely, those diagnosed beyond their mid-teens normally retain more beta-cells (despite still requiring daily insulin therapy).Early age at diagnosis has also been linked to increased risk of heart and kidney disease in later life. 

My observations in the pancreas have revealed that these endotypes differ immunologically (in the pancreas), and may hold a key to understanding how to ensure that the right people are included in the right trials so that we can move more rapidly to increasingly stratified treatment in T1D.

Unfortunately, age is not definitive, and we have very few clinically accessible clues that can inform us precisely what is happening in the pancreas as the insulin-producing beta-cells are destroyed. Therefore studies must be undertaken in the pancreas itself to address this knowledge gap.

I have recently been awarded a prestigious RD Lawrence Fellowship by Diabetes UK to advance this work. The research will explore the pancreatic landscapes in health and disease, at different ages and disease durations, incorporating state-of-the-art histology and imaging techniques with mathematical modelling to better understand the aetiology of this impactful condition. 

I have a deep commitment to supporting new and emerging scientists and as such, I sit on our faculty EDI and ECR committees and am an active and honest ally to anyone that asks. Additionally, I am also increasingly embedded in outreach initiatives and engaging with patient involvement and interest groups.

Awards

  • RD Lawrence Fellowship (2023-2027)
  • FHEA Fellowship
  • 11 Above and Beyond Awards (University of Exeter)
  • Excellence in Biology (University of Plymouth)

Research group links:

Department of Clinical and Biomedical Sciences

and Islet Biology Group (www.isletbiologyexeter.com)

Qualifications

  • 1st class Hons in Human Bioscience
  • PhD focussed on the Heterogeneity of the Pancreatic pathology in T1D
  • Fellow of the Higher Education Authority

Research group links

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Publications

Journal articles

Leete P, Oram R, McDonald T, Ziller C, Hattersley A, Richardson S, Morgan N (In Press). Studies of insulin and proinsulin in pancreas and serum support the existence of aetiopathological endotypes of type 1 diabetes associated with age at diagnosis. Diabetologia
Ifie E, Russell M, Dhayal S, Leete P, Sebastiani G, Nigi L, Dotta F, Marjomäki V, Eizirik D, Morgan N, et al (In Press). Unexpected subcellular distribution of a specific isoform of the Coxsackie and adenovirus receptor, CAR-SIV, in human pancreatic beta cells. Diabetologia
Torabi F, Vadakekolathu J, Wyatt R, Leete P, Tombs MA, Richardson CC, Boocock DJ, Turner MD, Morgan NG, Richardson SJ, et al (2023). Differential expression of genes controlling lymphocyte differentiation and migration in two distinct endotypes of type 1 diabetes. Diabet Med, 40(9). Abstract.  Author URL.
Boldison J, Hopkinson JR, Davies J, Pearson JA, Leete P, Richardson S, Morgan NG, Wong FS (2023). Gene expression profiling in NOD mice reveals that B cells are highly educated by the pancreatic environment during autoimmune diabetes. Diabetologia, 66(3), 551-566. Abstract.
Leete P (2023). Interview: Pia Leete. EMJ Diabetes
Hanna SJ, Thayer TC, Robinson EJS, Vinh NN, Williams N, Landry LG, Andrews R, Siah QZ, Leete P, Wyatt R, et al (2023). Single-cell RNAseq identifies clonally expanded antigen-specific T-cells following intradermal injection of gold nanoparticles loaded with diabetes autoantigen in humans. Frontiers in Immunology, 14 Abstract.
Leete P (2023). Type 1 diabetes in the pancreas: a histological perspective. Diabet Med, 40(12). Abstract.  Author URL.
Carr ALJ, Inshaw JRJ, Flaxman CS, Leete P, Wyatt RC, Russell LA, Palmer M, Prasolov D, Worthington T, Hull B, et al (2022). Circulating C-Peptide Levels in Living Children and Young People and Pancreatic β-Cell Loss in Pancreas Donors Across Type 1 Diabetes Disease Duration. Diabetes, 71(7), 1591-1596. Abstract.
Krogvold L, Leete P, Mynarek IM, Russell MA, Gerling IC, Lenchik NI, Mathews C, Richardson SJ, Morgan NG, Dahl-Jørgensen K, et al (2022). Detection of Antiviral Tissue Responses and Increased Cell Stress in the Pancreatic Islets of Newly Diagnosed Type 1 Diabetes Patients: Results from the DiViD Study. Frontiers in Endocrinology, 13 Abstract.
Rodriguez-Calvo T, Chen Y-C, Verchere CB, Haataja L, Arvan P, Leete P, Richardson SJ, Morgan NG, Qian W-J, Pugliese A, et al (2021). Altered β-Cell Prohormone Processing and Secretion in Type 1 Diabetes. Diabetes, 70(5), 1038-1050. Abstract.  Author URL.
Leete P, Morgan NG (2021). Footprints of Immune Cells in the Pancreas in Type 1 Diabetes; to "B" or Not to "B": is That Still the Question?. Front Endocrinol (Lausanne), 12 Abstract.  Author URL.
Russell M, Leete P (2019). Glucocorticoids: novel agents to stimulate beta-cell neogenesis?. Annals of Translational Medicine, 7(8).
Russell MA, Redick SD, Blodgett DM, Richardson SJ, Leete P, Krogvold L, Dahl-Jørgensen K, Bottino R, Brissova M, Spaeth JM, et al (2019). HLA Class II Antigen Processing and Presentation Pathway Components Demonstrated by Transcriptome and Protein Analyses of Islet β-Cells from Donors with Type 1 Diabetes. Diabetes, 68(5), 988-1001. Abstract.  Author URL.
Vecchio F, Lo Buono N, Stabilini A, Nigi L, Dufort MJ, Geyer S, Rancoita PM, Cugnata F, Mandelli A, Valle A, et al (2018). Abnormal neutrophil signature in the blood and pancreas of presymptomatic and symptomatic type 1 diabetes. JCI Insight, 3(18). Abstract.  Author URL.
Shields B, McDonald T, Oram R, Hill A, Hudson M, Leete P, Pearson E, Richardson S, Morgan N, Hattersley A, et al (2018). C-peptide decline in type 1 diabetes has two phases: an initial exponential fall and a subsequent stable phase. Diabetes Care
Colli ML, Hill JLE, Marroquí L, Chaffey J, Dos Santos RS, Leete P, Coomans de Brachène A, Paula FMM, Op de Beeck A, Castela A, et al (2018). PDL1 is expressed in the islets of people with type 1 diabetes and is up-regulated by interferons-α and-γ via IRF1 induction. EBioMedicine, 36, 367-375. Abstract.  Author URL.
Leete P, Mallone R, Richardson SJ, Sosenko JM, Redondo MJ, Evans-Molina C (2018). The Effect of Age on the Progression and Severity of Type 1 Diabetes: Potential Effects on Disease Mechanisms. Current Diabetes Reports, 18(11). Abstract.
Hodik M, Anagandula M, Fuxe J, Krogvold L, Dahl-Jørgensen K, Hyöty H, Sarmiento L, Frisk G, Atkinson M, Pugliese A, et al (2016). Coxsackie-adenovirus receptor expression is enhanced in pancreas from patients with type 1 diabetes. BMJ Open Diabetes Research and Care, 4(1). Abstract.
Leete P, Willcox A, Krogvold L, Dahl-Jørgensen K, Foulis AK, Richardson SJ, Morgan NG (2016). Differential Insulitic Profiles Determine the Extent of β-Cell Destruction and the Age at Onset of Type 1 Diabetes. Diabetes, 65(5), 1362-1369. Abstract.  Author URL.
Richardson SJ, Rodriguez-Calvo T, Gerling IC, Mathews CE, Kaddis JS, Russell MA, Zeissler M, Leete P, Krogvold L, Dahl-Jørgensen K, et al (2016). Islet cell hyperexpression of HLA class I antigens: a defining feature in type 1 diabetes. Diabetologia, 59(11), 2448-2458. Abstract.  Author URL.
Krogvold L, Edwin B, Buanes T, Frisk G, Skog O, Anagandula M, Korsgren O, Undlien D, Eike MC, Richardson SJ, et al (2015). Detection of a low-grade enteroviral infection in the islets of langerhans of living patients newly diagnosed with type 1 diabetes. Diabetes, 64(5), 1682-1687. Abstract.  Author URL.
Arif S, Leete P, Nguyen V, Marks K, Nor NM, Estorninho M, Kronenberg-Versteeg D, Bingley PJ, Todd JA, Guy C, et al (2015). Erratum. Blood and Islet Phenotypes Indicate Immunological Heterogeneity in Type 1 Diabetes. Diabetes 2014;63:3835-3845. Diabetes, 64(9).  Author URL.
Leete P, Richardson SJ, Krogvold L, Willcox A, Dahl-Jorgensen K, Foulis AK, Morgan NG (2015). Low B-lymphocyte numbers within the insulitic lesion correlates with an elevated proportion of persisting beta cells and later onset of disease in patients with Type 1 diabetes. DIABETIC MEDICINE, 32, 63-63.  Author URL.
Arif S, Leete P, Nguyen V, Marks K, Nor NM, Estorninho M, Kronenberg-Versteeg D, Bingley PJ, Todd JA, Guy C, et al (2014). Blood and islet phenotypes indicate immunological heterogeneity in type 1 diabetes. Diabetes, 63(11), 3835-3845. Abstract.  Author URL.
Richardson SJ, Leete P, Dhayal S, Russell MA, Oikarinen M, Laiho JE, Svedin E, Lind K, Rosenling T, Chapman N, et al (2014). Detection of enterovirus in the islet cells of patients with type 1 diabetes: what do we learn from immunohistochemistry? Reply to Hansson SF, Korsgren S, Pontén F et al [letter]. Diabetologia, 57(3), 647-649.  Author URL.
Leete P, Richardson SJ, Bone AJ, Foulis AK, Morgan NG (2014). Differential expression of anti-apoptotic B-cell lymphoma-2 (Bcl-2) family proteins by the islet endocrine cell subtypes in human pancreas. DIABETIC MEDICINE, 31, 47-48.  Author URL.
Richardson SJ, Leete P, Dhayal S, Russell MA, Oikarinen M, Laiho JE, Svedin E, Lind K, Rosenling T, Chapman N, et al (2014). Evaluation of the fidelity of immunolabelling obtained with clone 5D8/1, a monoclonal antibody directed against the enteroviral capsid protein, VP1, in human pancreas. Diabetologia, 57(2), 392-401. Abstract.  Author URL.
Morgan NG, Leete P, Foulis AK, Richardson SJ (2014). Islet inflammation in human type 1 diabetes mellitus. IUBMB Life, 66(11), 723-734. Abstract.  Author URL.
Richardson SJ, Leete P, Bone AJ, Foulis AK, Morgan NG (2013). Expression of the enteroviral capsid protein VP1 in the islet cells of patients with type 1 diabetes is associated with induction of protein kinase R and downregulation of Mcl-1. Diabetologia, 56(1), 185-193. Abstract.  Author URL.
Lind K, Richardson SJ, Leete P, Morgan NG, Korsgren O, Flodström-Tullberg M (2013). Induction of an Antiviral State and Attenuated Coxsackievirus Replication in Type III Interferon Treated Primary Human Pancreatic Islets. Journal of virology

Conferences

Wyatt RC, Leete P, Padilla M, Yang M, Bogdani M, Deutsch G, Flaxman C, Atkinson M, Kusmartseva I, Morgan NG, et al (2021). Using the HALO image analysis platform to study pancreas pathology and insulitis in young people with recent-onset type 1 diabetes.  Author URL.

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