Physiological Society recognises Dr Hills’ work with Joan Mott Prize Lecture

Reader at the School of Life Sciences, Dr Claire Hills, has been awarded the Physiological Society’s 2019 Joan Mott Prize Lecture.

The Lecture recognises a female physiologist for their long-term contribution to the field and is one of the Society’s most prestigious international awards. Claire joins a long list of renowned female international physiologists who have previously been awarded this Prize, including Professor Rhian Touyz (2017), Director of the Institute of Cardiovascular and Medical Sciences at the University of Glasgow and Professor Hannelore Daniel (2015), Chair of Physiology of Human Nutrition at the Technical University of Munich.

In addition to receiving an honorarium, Dr Hills will deliver the Prize Lecture to the Society’s main meeting in Aberdeen, Scotland. The Lecture will be published in the Society’s Journal, Experimental Physiology. 

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Diabetes UK to fund major new study aiming to prevent kidney disease

 
Diabetes UK to fund major new study aiming to prevent kidney diseaseCharity funding has been awarded for a major new study which will aim to prevent glucose-induced damage to kidney function in people with diabetes.Professor Paul Squires and Dr Claire Hills, from the School of Life Sciences at the University of Lincoln, UK, have been awarded a grant of more than £200,000 from Diabetes UK to examine how increased levels of glucose in people with diabetes can adversely affect kidney cell communications and contribute to the progression of kidney disease.

Their work will provide vital information about how kidney disease develops in people with diabetes, and ultimately help to alleviate and prevent the damage caused to normal kidney function by excess glucose.

“The UK prevalence of diabetes is predicted to increase from 2.9 million sufferers currently, to 5 million in 2025. Kidney complications now account for 21% of deaths in patients with type 1 diabetes and 11% of deaths in those with type 2,” Professor Squires explained. “Diabetic nephropathy – a debilitating and potentially life threatening complication of diabetes – is the leading cause of end-stage kidney disease, and to identify future treatment options in our fight against this condition, we need to understand the basic mechanisms that prevent kidney cells from functioning correctly. That is exactly what our new research will aim to do.”

In diabetes, sustained exposure to increased levels of glucose adds extra stress to normal kidney function. The resulting damage alters the basic characteristics of cells, making it impossible for them to fulfill their usual role. High levels of glucose cause the contacts between kidney cells to weaken, and as cells move apart they lose the ability to directly talk to each other. In the absence of advice from their immediate neighbours, cells begin to work independently and often respond inappropriately to normal signals.

This new research will examine how high levels of glucose affect the ability of the cells that line the small tubes of the kidney to communicate with each other and their surrounding environment.

Dr Hills said: “Through our previous research, we have already demonstrated that glucose reduces the stickiness between kidney cells. This loss of adherence impairs the way cells talk to one another and in turn, affects cell function. Importantly, we already have preliminary evidence which suggests that in patients with diabetic nephropathy, there is a change in expression of the proteins responsible for transferring information between kidney cells. In the absence of any information transfer, these cells are unable to respond effectively to changes in their immediate surroundings.”

The group’s research has found that as kidney cells begin to move apart, they rely less on direct cell-to-cell communication and switch to an alternative form of interaction that involves the release of local signals from pores in the cell’s membrane.

These pores (made up of proteins called connexins) have been linked to the onset of several diabetes-related complications. They release signaling molecules to enable communication, but sustained communication in this way has been linked to kidney scarring and fibrosis (excess connective tissue build up during repair process). Scarring and fibrosis are linked to loss of kidney function, and are recognised as precursors to kidney failure and the need for transplantation.

Dr Hills explained: “In an attempt to maintain a meaningful conversation, the release of ATP from cells actually contributes to the on-set of kidney disease. Our new project will therefore see us collaborate with a number of clinical partners and an international biotech company who are able to supply new agents to block ATP release. We hope that this project will help us to provide valuable information about how to alleviate and prevent damage to normal kidney function, and the onset of kidney disease.”

The new research project, entitled ‘Determining a role for connexin mediated cell communication in the progression of renal fibrosis in the diabetic kidney’, will run for three years and is part of an extensive portfolio of diabetes research at the University of Lincoln.

Researchers to present at leading diabetes conferences

The Diabetes Research Group from the School of Life Sciences, University of Lincoln, UK, will be presenting their latest research at two conferences hosted by Diabetes UK.

The first presentation will take place at the Midlands Volunteering Conference on Saturday, 28th February.

The event will bring together Diabetes UK volunteers from across the region, giving them a greater insight into the studies taking place in the Midlands.

The group, led by Professor Paul Squires, will provide an overview and update on current Diabetes UK-funded research at Lincoln and join a panel discussion.

Understanding and ultimately preventing renal damage in diabetes sufferers is a key aim for the group.

Professor Paul Squires and Dr Claire Hills, also from the University of Lincoln, are carrying out research supported by project and equipment grants from Diabetes UK.

Their joint research aims to better understand the sub-cellular mechanisms that regulate how people with diabetes can end up with diabetic nephropathy (kidney disease).

They are currently investigating how high glucose and an important down-stream pro-fibrotic cytokine called Transforming Growth Factor-beta (TGF-beta), cause renal damage as a result of this metabolic disease.

Dr Hills said: “Understanding the mechanism by which TGF-beta evokes its effects is essential in establishing novel therapeutic strategies for the prevention or arrest of the disease.”

The group will also be presenting their research at the Diabetes UK Professional Conference at the ExCeL London on 11th to 13th March.

The conference normally attracts more than 3,000 national and international delegates and is the largest event in the UK run exclusively for healthcare professionals and scientists working in the field of diabetes.

All abstracts will be published in Diabetic Medicine 33, 2015.

Professor Squires said: “The aim of this event is to describe how Diabetes UK funding has helped our research and to explain how the work will ultimately benefit people living with the condition.”

As part of the event, Professor Squires will also be chairing a State-of-the-Art session at the meeting entitled, ‘Latest Islet Biology’, which will examine recent developments in improving insulin secretion from pancreatic islets of Langerhans and new technologies geared to transplantation therapy using engineered beta-cells. The islets of Langerhans are the regions of the pancreas that contain its endocrine (hormone-producing) cells.

Further funding for diabetes research

A team from the University of Lincoln has been awarded 80,000 Euros to develop research to help improve understanding of the leading cause of end-stage kidney disease in diabetes patients.

The European Federation for the Study of Diabetes has awarded the Janssen Kidney Award to Dr Claire Hills and Professor Paul Squires, whose joint research aims to better understand the sub-cellular mechanisms that regulate how people with diabetes can end up with diabetic nephropathy (kidney disease).

As the leading cause of end-stage kidney disease, diabetic nephropathy is a debilitating and potentially life threatening complication of diabetes.

Every cell in the body is surrounded by a complex matrix of proteins that allows them to interact with each other and their immediate environment.

This extracellular matrix allows cells to detect survival signals in times of stress and has a crucial role in maintaining appropriate cell function. Changes to the matrix have been linked to a number of diseases, such as diabetes.

In the current study, Dr Hills and Professor Squires will examine how glucose and associated cytokines (small proteins that are important in cell signalling) reduce ‘stickiness’ between neighbouring cells of the proximal kidney and between cells and their surrounding matrix.

Dr Hills said: “Little is known about the mechanisms through which these glucose-induced detrimental effects occur, however, we believe that a loss of these interactions changes the behaviour of cells and contributes to the high level of damage seen in diabetes.”

With the help of international collaborators, biopsy material from both healthy kidneys and those obtained from patients with diabetic nephropathy will ensure that work accurately models the situation in humans.

Dr Hills added: “To identify future therapeutic targets in our fight against the increasing prevalence of this condition, we need to understand the basic mechanisms that prevent kidney cells from functioning correctly.”

The research will improve understanding of why renal function is often impaired in diabetes and will identify pathways that may alleviate and/or prevent glucose-induced damage of normal kidney function.

For additional information please see: http://www.europeandiabetesfoundation.org/index.php/ct-menu-item-9/14-sample-data-articles/173-recipient

Grant award to help treat renal disease in diabetes sufferers

Research by Dr Claire Hills, from the School of Life Sciences, aims to better understand the sub-cellular mechanisms that regulate how people with diabetes can end up with diabetic nephropathy (kidney disease).

Dr Hills has been awarded an £18,000 grant from the Diabetes Research and Wellness Foundation (DRWF) to help identify a future therapeutic target for alleviating renal fibrosis in diabetes.

Almost one third of all patients with diabetes progressively develop diabetic nephropathy within 10-to-30 years of the onset of disease and this accounts for almost a quarter of those entering renal replacement programs in the UK.

However, we still lack a basic understanding of how this debilitating condition develops.

Dr Hills said: “In the diabetic kidney, a build-up of fibrotic material, in part, brings about both structural and functional damage culminating in loss of both cell integrity and function. Damage occurs when cells fail to respond as they should, and thus start behaving more characteristic of cells of another tissue type. In doing so, cells lose their ability to synchronise their activity with neighbouring cells. They become less able to directly adhere to surrounding cells and to the extracellular matrix; a skeleton, which surrounds and supports the cell. Loss of these interactions results in failure of transmission of cell survival signals. However, basic knowledge on how matrix reorganisation impacts on kidney function in diabetes is severely lacking.”

The study entitled “Does reorganisation of the extracellular matrix promote glucose induced fibrosis in diabetic nephropathy” will use healthy and diseased cells to establish how high glucose and an important down-stream pro-fibrotic cytokine called Transforming Growth Factor-beta (TGF-beta), both regulate and disrupt cell-cell and cell-matrix interactions.

Changes observed in response to glucose-evoked TGF-β1 will help identify target areas for further research and may have a tangible effect on directing pharmaceutical research and development and for the future treatment of diabetic nephropathy within a 10 to 15 year time frame.