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Dr Pia Leete

Senior Research/ RD Lawrence Fellow

 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 multifaceted nature of 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", tends to be diagnosed in early life (<10y), and is linked to a more profound loss of beta-cells. Early age at diagnosis has also been linked to other, more serious outcomes, in later life, such as increased risk of heart and kidney disease. Conversely, those diagnosed beyond their mid-teens normally retain more beta-cells (despite still requiring daily insulin therapy). My observations in the pancreas have also revealed that these endotypes also differ immunologically (in the pancreas). These observations may hold a key to understanding how to ensure that the right people are included in right trials and ensure that we can move more rapidly to personalised care in T1D.

Unfortunately, age is not definitive and at present we have very few clinically accessible clues that can inform us precisely what is happening  as the insulin producing beta-cells are destroyed in the pancreas. Therefore, further work to  critical if we are to leverage enough information to support the development of targeted and patient-specific therapies aiming to improve long-term health for individuals at risk of, or already diagnosed with, Type 1 diabetes.

I have recently been awarded a prestigious RD Lawrence Fellowship by Diabetes UK to advance this work. The research will continue to explore the pancreatic landscapes in health and disease, at different ages and disease durations, and will also include mathematical modelling to understand the aetiology of this impactful condition. There will also be a period of training with Dr Catherine Arden and Professor Jim Shaw at Newcastle University to learn and develop protocols in the UK to employ the “living slice technology” in my work.

I have had the pleasure of developing my career and working alongside members of the IBEx group for 10 years. During this time, I have been fortunate to work in a team that has supported my growth as a professional, scientist and human begin; and as such, I have a deep commitment to supporting new and emerging scientists to experience the same – no matter who they are. As such, I sit on our faculty EDI committee, ECR committee, and am active LGBTQ+ ally. 

Additionally, I beleive that understanding our own health empowers us to work with it; and with this deep belief, I am also increasingly embedded in outreach initiatives and engaging with patient involvement and interest groups.

Qualifications

  • 1st class Hons in Human Biosciences
  • PhD focussed on the Heterogeneity of the Pancreatic pathology in Type 1 diabetes
  • Fellow of the Higher Education Authority

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

Research

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.
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


Pia_Leete Details from cache as at 2023-09-29 20:16:48

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