Peter Jones

Peter Jones

Professor

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    Biographical details

    CAREER SYNOPSIS

    Peter Jones is Professor of Endocrine Biology in the Diabetes Research Group at the Guy’s campus of King’s College London.  Peter obtained his PhD at the National Institute for Medical Research (London) studying peptide hormones in the central nervous system.  He started working on β-cell function in diabetes as a postdoctoral fellow at Queen Elizabeth College in 1984. He was awarded an R.D. Lawrence Fellowship by the British Diabetic Association, followed by a Medical Research Council Senior Research Fellowship, after which he took up an academic position as Lecturer in Physiology at King’s. He was awarded the British Diabetic Association R.D. Lawrence Lecture for 1997 and the Dorothy Hodgkin Lecture for 2015 in recognition of his work on β-cell function. His research interests remains with the β-cell, with current focus on developing strategies to improve the outcomes of islet transplantation therapy for Type 1 diabetes and on novel therapeutic targets for Type 2 diabetes. 

     

    EDUCATION

    1975-1979: University of Coventry. BSc  in Applied Biology (1st class), incorporating sandwich year at National Institute for Biological Standards and Control.

    1979-1982:  National Institute for Medical Research, London PhD in Physiology (London). “Neurohypophysial peptides in cerebrospinal fluid”, awarded 1983  

     

    POST-DOCTORAL POSITIONS

    1982-1984:   National Institute for Medical Research, London.

    1984-1987:   Department of Physiology, Queen Elizabeth College, London (MRC)

    1987-1989:   Biomedical Sciences Division, King's College London. R.D. Lawrence Fellow of the British Diabetic Association.  

    1989-1993:   Biomedical Sciences Division, King's College London. Medical Research Council Senior Research Fellow (Non-Clinical).

     

    ACADEMIC POSITIONS

    1993-1999:   Lecturer in Physiology,Biomedical Sciences Division, King's College London.

    1999-2004:   Reader in Endocrinology and Metabolism , School of Biomedical Sciences, King's College London.

    2004- present Professor of Endocrine Biology, King's College London.

    2016-present Head, Depoartment of Physiology, King's College London.

    Research interests (short)

    • Regulation of endocrine cell function
    • Cell-cell interactions in regulation of hormone secretion
    • Regulation of islet function
    • Improving islet transplantation outcomes
    • Regulation of beta-cell mass
    • Generating functional beta-cells from stem cells for transplantation

    Research interests

    Cell-cell interactions in the regulation of islet function

    Cell-cell interactions within islets are vital for maintaining normal islet function, but the precise nature of these interactions is still unclear. Understanding the functional basis of cell-cell interactions within islets is important when considering the secretory defects in Type 2 diabetes and in designing islet substitutes for transplantation therapy of Type 1 diabetes.   We currently use a number of experimental models to study what these interactions are, and how they influence islet function.

     

    Our studies have demonstrated that interactions between islet endocrine cells are vital for maintaining normal patterns of hormone secretion.  For example, we have used the insulin-secreting MIN6 b-cell line to develop methods for creating three-dimensional islet-like organs in vitro. These structures, that we call pseudoislets, are anatomically and functionally similar to primary islets of Langerhans and we are using then to investigate how cell-cell interaction influence cell function in terms of insulin secretion, cell proliferation and apoptosis.   We also use genetically-modified models to study paracrine interactions within islets. For example,   somatostatin (SST) is a peptide hormone made and secreted by the delta cells of the islets of Langerhans, and we are using a somatostatin gene knock-out mouse model to investigate the role of SST in islet development and the regulation of insulin secretion. These studies are primarily directed by Dr Astrid Hauge-Evans who is a RD Lawrence Research Fellow funded by Diabetes UK. 

     

    The islets of Langerhans have an extensive blood supply and this is very important for their correct functioning. It is well known that islets of Langerhans function as integrated organs (see above), and the endocrine cells in the islets (such as the insulin-secreting β-cells) can influence the function of the endothelial cells in the blood vessels, and vice versa.  We are studying the functional consequences of cellular interactions between islet endocrine and endothelial cells (ECs) by characterising the phenotype of endothelial cells isolated from rodent and human islets; by studying the factors influencing the development and maintenance of the islet endothelial phenotype; and by determining the effects of direct endothelial-endocrine cell interactions via cell surface molecules on islet function.2 Enhancing islet EC survival and function in islet transplants may improve transplantation outcomes, so a fuller understanding of the interactions between islet endocrine cells and islet endothelial cells may enable the refinement of transplantation therapies to ensure rapid and effective functional engraftment.  These studies are performed in collaboration with an endothelial cell biologist, Professor Caroline Wheeler-Jones who is based at the Royal Veterinary College, London.  

     

     

    Regulation of the functional β-cell mass

    Type 2 diabetes is associated with impaired β-cell function and a reduced β-cell mass, so we are exploring experimental strategies for maintaining or expanding the functional β-cell mass. Current focus is on using in vivo and in vitro models to identify novel signals which regulate (patho)physiological changes in the  β-cell mass during the development of obesity, and during normal pregnancy.  We are using targeted gene arrays to identify novel secreted factors and to match them with changes in β-cell receptor expression in response to changes in metabolic demand.  This work is in collaboration with Professor Shanta Persaud and Dr James Bowe, and it may lead to novel therapeutic approaches for the treatment of Type 2 diabetes.   

     

    Stem cells and islet function

    We are interested in the therapeutic potential of stem cell populations in the treatment of diabetes, with research projects using both embryonic stem cells (ESCs) and mesenchymal stem cells (MSCs). 

     

    Recent developments suggest that transplantation of primary islets of Langerhans may offer a cure for type 1 diabetes.  Primary islet transplant material from human donors will not provide sufficient tissue to treat more than a fraction of people with diabetes so we are investigating the potential of ESCs and/or MSCs as starting material from which to generate in vitro insulin-secreting b-cells. The ultimate aim of these studies is the production from human progenitor cells of transplant material that functions like normal human b-cells and is suitable for use in the clinical treatment of diabetes mellitus.

     

    A major problem with current islet transplantation protocols is the loss of islet function in the immediate post-transplantation period. We have demonstrated recently that co-transplanting MSCs with islets improves the rate and extent of curing the symptoms of diabetes in graft recipients, effects that are associated with improved revascularisation of the graft and with the maintenance of anatomical integrity of the engrafted islets. Our current studies have demonstrated that pre-treatment of islet with MSCs prior to transplantation is alone sufficient to confer beneficial effects on islet function and transplantation outcomes,and we are currently investigating the molecular mechanisms underlying these beneficial effects using in vitro models of cell-cell interactions and in vivo models of islet transplantation with Dr Aileen King.  

     

    Encapsulation strategies for cell therapy

    Many of the current problems with clinical islet transplantation as a therapy for Type 1 diabetes are directly or indirectly related to interactions between the donor islet graft and the immunologically dissimilar host environment.   These problems could be alleviated by maintaining a biocompatible barrier between the islet graft and the host environment. We are currently developing novel mechanisms for generating and maintaining such a barrier. Islet encapsulation strategies to date have mainly focused on gel-based capsules (microencapsulation). These are effective in hiding the encapsulated islets from the host immune system but the relatively large capsule size causes survival problems for the islets, and places a physical limit on where they can be implanted.   In parallel studies we are also  developing methods for coating islets with very thin (nanometer thick) layers of charged molecules, and of forming intact capsules around the islets by applying multiple layers of the coating (nanoencapsulation).The coating does not affect the survival or function of the islets and they are able to sense change in glucose and to secrete appropriate amounts of insulin. Both micro- and nanoencapsulated islets reverse experimental diabetes in a mouse model, and protect the islets from being rejected by the host immune system. In addition, nanocapsules can be modified to deliver drugs or other biological molecules to protect the islets after implantation in the host, and so improve survival of the islet in the important post-transplantation period. We are now investigating the incorporation of anti-inflammatory and/or antithrombotic molecules into the nanocapsules to protect the islets from deleterious stimuli.   

     

    This work is currently performed by Dr Zheng-Liang Zhi funded by the Juvenile Diabetes Research Foundation, and it may lead to improvements in the protocols for clinical islet transplantation in people with Type 1 diabetes, and so improve transplantation outcomes. In the longer term we aim to extend the nanoencapsulation strategy to other clinically applicable cell therapies, including the transplantation of hepatocytes and stem cell populations.  

    Expertise related to UN Sustainable Development Goals

    In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):

    • SDG 3 - Good Health and Well-being
    • SDG 16 - Peace, Justice and Strong Institutions

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