̽��ֱ�� of Cambridge - Department of Haematology

Mouse study suggests a common diabetes drug may prevent leukaemia

cjb250 — Wed, 16 Apr 2025 07:59:00 +0000

Around 3,100 people are diagnosed with acute myeloid leukaemia (AML) each year in the UK. It is an aggressive form of blood cancer that is very difficult to treat. Thanks to recent advances, individuals at high risk of AML can be identified years in advance using blood tests and blood DNA analysis, but there’s no suitable treatment that can prevent them from developing the disease.

In this study, Professor George Vassiliou and colleagues at the ̽��ֱ�� of Cambridge investigated how to prevent abnormal blood stem cells with genetic changes from progressing to become AML. ̽��ֱ��work focused on the most common genetic change, which affects a gene called DNMT3A and is responsible for starting 10-15% of AML cases.

Professor Vassiliou, from the Cambridge Stem Cell Institute at the ̽��ֱ�� of Cambridge and Honorary Consultant Haematologist at Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust (CUH) co-led the study. He said: “Blood cancer poses unique challenges compared to solid cancers like breast or prostate, which can be surgically removed if identified early. With blood cancers, we need to identify people at risk and then use medical treatments to stop cancer progression throughout the body.”

̽��ֱ��research team examined blood stem cells from mice with the same changes in DNMT3A as seen in the pre-cancerous cells in humans. Using a genome-wide screening technique, they showed that these cells depend more on mitochondrial metabolism than healthy cells, making this a potential weak spot. ̽��ֱ��researchers went on to confirm that metformin, and other mitochondria-targeting drugs, substantially slowed the growth of mutation-bearing blood cells in mice. Further experiments also showed that metformin could have the same effect on human blood cells with the DNMT3A mutation.

Dr Malgorzata Gozdecka, Senior Research Associate at the Cambridge Stem Cell Institute and first author of the research said: “Metformin is a drug that impacts mitochondrial metabolism, and these pre-cancerous cells need this energy to keep growing. By blocking this process, we stop the cells from expanding and progressing towards AML, whilst also reversing other effects of the mutated DNMT3A gene.”

In addition, the study looked at data from over 412,000 UK Biobank volunteers and found that people taking metformin were less likely to have changes in the DNMT3A gene. This link remained even after accounting for factors that could have confounded the results such as diabetes status and BMI.

Professor Brian Huntly, Head of the Department of Haematology at the ̽��ֱ�� of Cambridge, Honorary Consultant Haematologist at CUH, and joint lead author of the research, added: “Metformin appears highly specific to this mutation rather than being a generic treatment. That specificity makes it especially compelling as a targeted prevention strategy.

“We’ve done the extensive research all the way from cell-based studies to human data, so we’re now at the point where we have a made a strong case for moving ahead with clinical trials. Importantly, metformin’s lack of toxicity will be a major advantage as it is already used by millions of people worldwide with a well-established safety profile.”

̽��ֱ��results of the study, funded by Blood Cancer UK with additional support from Cancer Research UK, the Leukemia & Lymphoma Society (USA) and the Wellcome Trust, are published in Nature.

Dr Rubina Ahmed, Director of Research at Blood Cancer UK, said: “Blood cancer is the third biggest cancer killer in the UK, with over 280,000 people currently living with the disease. Our Blood Cancer Action plan shed light on the shockingly low survival for acute myeloid leukaemia, with only around 2 in 10 surviving for 5 years, and we urgently need better strategies to save lives. Repurposing safe, widely available drugs like metformin means we could potentially get new treatments to people faster, without the need for lengthy drug development pipelines.”

̽��ֱ��next phase of this research will focus on clinical trials to test metformin’s effectiveness in people with changes in DNMT3A at increased risk of developing AML. With metformin already approved and widely used for diabetes, this repurposing strategy could dramatically reduce the time it takes to bring a new preventive therapy to patients.

Tanya Hollands, Research Information Manager at Cancer Research UK, who contributed funding for the lab-based screening in mice, said: “It's important that we work to find new ways to slow down or prevent AML in people at high risk. Therefore, it’s positive that the findings of this study suggest a possible link between a commonly-used diabetes drug and prevention of AML progression in some people. While this early-stage research is promising, clinical trials are now needed to find out if this drug could benefit people. We look forward to seeing how this work progresses.”

Reference
Gozdecka, M et al. Mitochondrial metabolism sustains DNMT3A-R882-mutant clonal haematopoiesis. Nature; 16 Apr 2025; DOI: 10.1038/s41586-025-08980-6

Adapted from a press release from Blood Cancer UK

Metformin, a widely used and affordable diabetes drug, could prevent a form of acute myeloid leukaemia in people at high risk of the disease, a study in mice has suggested. Further research in clinical trials will be needed to confirm this works for patients.

We’ve done the extensive research all the way from cell-based studies to human data, so we’re now at the point where we have a made a strong case for moving ahead with clinical trials

Brian Huntly

̽��ֱ�� of Cambridge

Brown lab mouse on blue gloved hand

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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New way to extend ‘shelf life’ of blood stem cells will improve gene therapy

lmp58 — Thu, 15 Aug 2024 14:47:37 +0000

Researchers have identified a drug already used for cancer patients, that, when applied to current gene therapy protocols can improve blood stem cell function threefold.

One trillion blood cells are produced every day in humans, and blood stem cells are the only cell types in our body capable of producing all blood cell types over our lifespan, giving them immense regenerative potential.

Blood stem cell gene therapy is a ground-breaking treatment that currently provides the only cure to more than ten life-debilitating genetic diseases and has already saved the lives of more than two million people with blood cancers and other diseases.

These therapies take blood stem cell samples from patients, where their genetic defect is corrected in a dish before being delivered back to the patient. However, limitations persist in blood stem cell therapies because of the shelf life of the cells outside the body. When removed from their environment in the human body and cultured in a dish, most blood stem cells lose their function. ̽��ֱ��exact timing and cause of this function loss has not previously been well understood.

Now, scientists in the Laurenti Group and others at the ̽��ֱ�� of Cambridge’s Cambridge Stem Cell Institute (CSCI) and Department of Haematology have pinpointed a timeline for the blood stem cells under the current gene therapy protocols, which typically take place over three days. After the first 24 hours in a dish, more than 50% of the blood stem cells can no longer sustain life-long blood production, which is before therapy would even begin in a clinical setting.

During those first 24 hours, the cells activate a complex molecular stress response in order to adapt to the dish. By studying this stress response, the team identified a solution. Through repurposing a cancer growth blocker drug (Ruxolitinib), already in use for cancer treatments, they were able to improve stem cell function in a dish by three times its former capabilities.

̽��ֱ��group is now aiming to modify current gene therapy protocols to include this drug, providing patients with the highest number of high-quality blood stem cells and improving their outcomes.

̽��ֱ��study is published today in the journal Blood.

Professor Elisa Laurenti at the ̽��ֱ�� of Cambridge Stem Cell Institute, and senior author of the study, said: “This is really exciting because we are now in a position where we can begin to understand the huge stress that these stem cells sense when they are manipulated outside of our body. Biologically it is really fascinating because it affects every aspect of their biology. Luckily, we were able to identify a key molecular pathway which governs many of these responses, and that can be targeted by a drug which is already in use and is safe to use.

“I hope our findings will enable safer treatments for gene therapy patients. Our discovery also opens up many possibilities to better expand blood stem cells ex vivo and expand the set of disease where we can use blood stem cells to improve patients’ lives.”

Dr Carys Johnson at the ̽��ֱ�� of Cambridge Stem Cell Institute, and first author of the study, said: “Although we expected that removing these cells from the body and culturing them on a plastic surface would alter gene expression, the extent of change we found was surprising, with over 10,000 genes altered and a significant stress response detected. It was also striking to discover that the majority of blood stem cells are functionally lost during gene therapy protocols, before transplantation back to the patient.

“We have identified a key bottleneck where function is lost and clinical culture could be improved. I hope that our work will drive advancements in culture protocols to better harness the power of blood stem cells and improve the safety and efficacy of clinical approaches.”

Reference

C.S. Johnson, M.J. Williams, K. Sham, et al. ‘Adaptation to ex vivo culture reduces human hematopoietic stem cell activity independently of cell cycle.’ Blood 2024; DOI: 10.1182/blood.2023021426

Story written by Laura Puhl, Cambridge Stem Cell Institute.

Researchers have discovered a way to extend the shelf life of blood stem cells outside the body for use in gene therapy, providing patients with better options and improving their outcomes.

We were able to identify a key molecular pathway...that can be targeted by a drug which is already in use and is safe to use.

Elisa Laurenti

Philippe Delavie from Pixabay

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Role of inherited genetic variants in rare blood cancer uncovered

jg533 — Wed, 17 Jan 2024 10:03:16 +0000

Large-scale genetic analysis has helped researchers uncover the interplay between cancer-driving genetic mutations and inherited genetic variants in a rare type of blood cancer.

Researchers from the ̽��ֱ�� of Cambridge, Wellcome Sanger Institute, and collaborators, combined various comprehensive data sets to understand the impact of both cancer-driving spontaneous mutations and inherited genetic variation on the risk of developing myeloproliferative neoplasms (MPN).

̽��ֱ��study, published in the journal Nature Genetics, describes how inherited genetic variants can influence whether a spontaneous mutation in a particular gene increases the risk of developing this rare blood cancer.

This analysis has an impact on current clinical predictions of disease development in individuals. Further research is required to understand the biological mechanisms behind how these inherited genetic variants influence the chances of developing rare blood cancer. In the future, this knowledge could aid drug development and interventions that reduce the risk of disease.

Myeloproliferative neoplasms, MPNs, are a group of rare, chronic, blood cancers. There are around 4,000 cases of MPN in the UK each year. These occur when the bone marrow overproduces blood cells, which can result in blood clots and bleeding. MPNs can also progress into other forms of blood cancer, such as leukaemia.

In the population, there is a large amount of natural variation between individuals’ blood cells, which can affect the amount of blood cells a person has and their particular traits. This is because multiple different genes can influence blood cell features in an individual. During routine blood tests, researchers take known information about these genes and analyse the variation to give a genetic risk score, which is how likely that individual is to develop a disease over their lifetime.

MPNs have been linked to random somatic mutations in certain genes including in a gene called JAK2. However, mutated JAK2 is commonly found in the global population, and the vast majority of these individuals do not have or go on to develop MPN.

Whilst previous studies have identified over a dozen associated inherited genetic variants that increase the risk of MPN, these studies insufficiently explain why most individuals in the population do not go on to develop MPN.

This new study, from the Wellcome Sanger Institute and collaborators, combined information on the known somatic driver mutations in MPN, inherited genetic variants, and genetic risk scores from individuals with MPN.

They found that the inherited variants that cause natural blood cell variation in the population also impact whether a JAK2 somatic mutation will go on to cause MPN. They also found that individuals with an inherited risk of having a higher blood cell count could display MPN features in the absence of cancer-driving mutations, thus, mimicking disease.

Dr Jing Guo, from the ̽��ֱ�� of Cambridge and the Wellcome Sanger Institute and first author of the study, said: “Our large-scale statistical study has helped fill the knowledge gaps in how variants in DNA, both inherited and somatic, interact to influence complex disease risk. By combining these three different types of datasets we were able to get a more complete picture of how these variants combine to cause blood disorders.”

Professor Nicole Soranzo, co-senior author from the ̽��ֱ�� of Cambridge, the Wellcome Sanger Institute, and Human Technopole, Italy, said: “There has been increasing realisation that human diseases have complex causes involving a combination of common and rare inherited genetic variants with different severity.

“We have previously shown that variation in blood cell parameters and function has complex genetic variability by highlighting thousands of genetic changes that affect different gene functions. Here, we show for the first time that common variants in these genes also affect blood cancers, independent of causative somatic mutations. This confirms a new important contribution of normal variability beyond complex disease, contributing to our understanding of myeloproliferative neoplasms and blood cancer more generally.”

Dr Jyoti Nangalia, co-senior author from the Wellcome-MRC Cambridge Stem Cell Institute at the ̽��ֱ�� of Cambridge, and the Wellcome Sanger Institute, said: “We have a good understanding of the genetic causes of myeloproliferative neoplasms. In fact, many of these genetic mutations are routine diagnostic tests in the clinic. However, these mutations can often be found in healthy individuals without the disease.

“Our study helps us understand how inherited DNA variation from person to person can interact with cancer-causing mutations to determine whether disease occurs in the first place, and how this can alter the type of any subsequent disease that emerges. Our hope is that this information can be incorporated into future disease prediction efforts.”

This research was funded by Cancer Research UK and Wellcome.

Reference

J Guo, K Walter, P M Quiros, et al. ‘Inherited polygenic effects on common hematological traits influence clonal selection on JAK2V617F and the development of myeloproliferative neoplasms.’ Jan 2024, Nature Genetics. DOI: 10.1038/s41588-023-01638-x

Adapted from a press release by the Wellcome Sanger Institute

Combining three different sources of genetic information has allowed researchers to further understand why only some people with a common mutation go on to develop rare blood cancer.

Our hope is that this information can be incorporated into future disease prediction efforts

Jyoti Nangalia

Photo by Sangharsh Lohakare on Unsplash

DNA

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Scientists develop test to identify people at risk of developing acute myeloid leukaemia and related cancers

jg533 — Thu, 24 Aug 2023 15:14:28 +0000

Researchers at the Wellcome-MRC Cambridge Stem Cell Institute (CSCI), the ̽��ֱ�� of Cambridge’s Department of Haematology, and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA) analysed data from more than 400,000 individuals participating in the United Kingdom Biobank.

Using this data, the scientists created 'MN–predict', a platform for predicting the risk of developing blood cancers such as acute myeloid leukaemia, myelodysplastic syndromes and myeloproliferative neoplasms over a 10- to 15-year period.

̽��ֱ��test, now available in NHS clinics, requires patients to provide a blood sample from which DNA is extracted for limited sequencing, alongside basic blood cell counts. With this information, MN-predict identifies those at high risk of any of these cancers and can be used in specialist clinics for leukaemia prevention.

Professor George Vassiliou, senior author of the study, said: “We all know that prevention is better than cure, but it is not easy to prevent diseases like leukaemia without knowing who is at risk. MN-predict makes it possible to identify at-risk individuals, and we hope it can become an essential part of future leukaemia prevention programmes.”

̽��ֱ��myeloid neoplasms are a group of related cancers encompassing acute myeloid leukaemia, myelodysplastic syndromes and myeloproliferative neoplasms. Treatments for these cancers have improved in the last few years, but most cases remain incurable.

In the last few years, scientists have discovered that these cancers develop over decades through the accumulation of DNA mutations in blood stem cells - the cells responsible for normal blood formation. ̽��ֱ��mutations encourage these stem cells to grow faster than normal and, as more mutations accumulate, they can progress towards leukaemia.

While mutations that promote cell growth are common, leukaemia develops only in a small minority of cases. Identifying these cases early on helps efforts to prevent the cancers from developing.

̽��ֱ��work is published today in the journal Nature Genetics.

Dr Muxin Gu, first author of the paper, said: “We hope that MN-predict will help clinicians to identify people at risk of myeloid cancers, and use novel treatment to prevent the cancers developing.”

Dr Pedro M Quiros, joint senior author of the study, said: “Despite some recent advances in their treatment, unfortunately these cancers remain lethal to many sufferers. We hope that our efforts will help advance prevention in favour of treating the full-blown disease.”

̽��ֱ��research and development of MN-Predict was funded by Cancer Research UK and the Leukaemia and Lymphoma Society. Scientists from the Early Cancer Institute, ̽��ֱ�� of Cambridge, ̽��ֱ�� of Bristol, ̽��ֱ�� of Oviedo (Spain), ̽��ֱ�� of York, AstraZeneca (UK), German Cancer Research Center (DKFZ, Germany), St James's Hospital, Leeds (UK) and ̽��ֱ�� of Pavia (Italy) also participated in the study.

Reference

Gu M, Cheloor-Kovilakam S, Dunn W, Marando L, Barcena C, Mohorianu I, Smith A, Kar S, Fabre M, Gerstung M, Cargo C, Malcovati L, Quiros P, Vassiliou G: 'Multiparameter prediction of myeloid neoplasia risk.' Nature Genetics. 2023. DOI: 10.1038/s41588-023-01472-1

Adapted from a press release by the Wellcome-MRC Cambridge Stem Cell Institute.

̽��ֱ��new ‘MN-predict’ platform will allow doctors and scientists to identify those at risk and to design new treatments to prevent them from developing these potentially lethal cancers.

MN-predict makes it possible to identify at-risk individuals, and we hope it can become an essential part of future leukaemia prevention programmes.

George Vassiliou

Nguyễn Hiệp on Unsplash

Person having a blood test

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Cambridge researchers awarded European Research Council Consolidator Grants

cg605 — Tue, 31 Jan 2023 16:00:25 +0000

̽��ֱ��ERC is the premier European funding organisation for excellent frontier research. This year it has awarded €657m in grants to 321 researchers across Europe.

Consolidator grants are given to excellent scientists, who have 7 to 12 years’ experience after their PhDs, to pursue their most promising ideas.

“ERC Consolidator grants support researchers at a crucial time of their careers, strengthening their independence, reinforcing their teams and helping them establish themselves as leaders in their fields,” said President of the European Research Council Professor Maria Leptin. “And this backing above all gives them a chance to pursue their scientific dreams.”

Cambridge awardees:

Dr Eloy de Lera Acedo, STFC Ernest Rutherford Fellow at Cavendish Astrophysics and the Kavli Institute for Cosmology of the Department of Physics, has been awarded a grant for REACH_21: Probing the Cosmic Dawn and Epoch of Re-ionization with the REACH experiment.

De Lera Acedo said: “REACH_21 aims to unveil the mysteries of the infant universe. We want to answer the question: how did the cosmos, that evolved from the Big Bang, become the complex and luminous realm of celestial objects we can see from planet Earth today?

“This unknown missing piece in the puzzle of the history of the universe is now closer to being understood thanks to a new experimental approach that attempts to observe extremely faint radio signals emitted nearly 13.5 billion years ago by the most abundant element at that time: Neutral Hydrogen.”

“This is amazing news for the REACH collaboration. We have been designing our experiment for over five years and are currently awaiting the start of scientific observations in South Africa. ̽��ֱ��ERC grant is going to allow me to use the REACH telescope, analyse its data, and hopefully access a whole new world of information about the early evolution of the cosmos.”

Dr Daniel Hodson, of the Department of Haematology, has been awarded a grant for Unwind-Lymphoma: RNA helicases; switched paralogue dependency as an exploitable vulnerability in aggressive B cell lymphoma.

Hodson said: “This ERC-funded project, Unwind Lymphoma, will explore sex-specific, cancer cell addiction to the DDX3 family of RNA helicases, proteins that unwind secondary structure in mRNA.

“We will develop recent findings from our lab showing that whilst most male Burkitt lymphoma cells have deleted the X-chromosome gene DDX3X, they instead become uniquely addicted to the Y-chromosome paralogue DDX3Y, a related protein that is silenced in most normal cells. By unravelling the molecular basis of this ‘switched paralogue dependency’ we will expose a potential therapeutic Achilles Heel in this devastating form of blood cancer.

“I am thrilled to receive this award, which I hope will take me one step closer to a tenured position in Cambridge or beyond.”

Sohini Kar-Narayan, Professor of Device and Energy Materials of the Department of Materials Science and Metallurgy, has been awarded a grant for BIOTRONICA: Bio-Electronic Integrated Devices for Healthcare Applications.

Kar-Narayan said: “My research focuses on the development and characterisation of novel functional polymers and nanocomposites, and their application in functional devices using microscale additive manufacturing methods. It covers novel energy harvesting nanomaterials to microfluidic biosensors, to materials and devices for next-generation flexible and wearable electronics.

“I am absolutely delighted to have been awarded a Consolidator Grant to develop new tools for remote health monitoring and personalised medicine. These include novel non-invasive ‘point-of-care’ biosensors, which could potentially be self-powered through energy harvested from the body, thus enabling a step change in health monitoring and patient care.”

Dr Elisa Laurenti, ̽��ֱ�� Associate Professor in Stem Cell Medicine and Wellcome Royal Society Sir Henry Dale Fellow of the Wellcome Medical Research Council Cambridge Stem Cell Institute and Department of Haematology, has been awarded a grant for HEXAGEN: Harnessing haematopoietic stem cell EX vivo Adaptation for GENe therapy.

Laurenti said: “Blood stem cell-based gene therapy has the potential to cure an expanding range of debilitating genetic diseases. HEXAGEN seeks to further improve gene therapies and their outcomes by overcoming the loss of stem cell function observed in current clinical protocols. Using cutting edge single cell technologies, we aim to identify how blood stem cells adapt to the invitro environment, dissect how this negatively impacts their function, and design new strategies to improve gene therapy.

“This award gives my team the unique opportunity to be ambitious and complete a full circle from basic stem cell biology to improving gene therapy for patients with many diseases. I am very excited, because unlocking blood stem cell behaviour outside our bodies will also drive many other clinical applications.”

Dr Naomi McGovern, of the Department of Pathology and the Centre for Trophoblast Research, has been awarded a grant for PMDR: Placental macrophages: Their development and role in the placenta.

McGovern said: “My team’s research focus is human placental macrophage biology. We are interested in determining the role of these cells in mediating healthy placental function and in protecting the placenta from infection. By developing our understanding of these cells, we will be able to provide new insight into pregnancy disorders.

“I am delighted that our proposal was selected for an ERC Consolidator Award. It is an acknowledgement of the exciting research my team carries out. ̽��ֱ��hard work of my team and the additional expertise provided by our supportive collaborators all helped to form the basis for this proposal. ̽��ֱ��award will provide my group with the time and resources to undertake high-risk research to inform on placental biology. It is now up to us to deliver on this generous investment.”

Professor Robert Phipps, of the Yusuf Hamied Department of Chemistry, has been awarded a grant for IonPairEnantRadical: Transforming Enantioselective Radical Chemistry using Ion-Pairing Catalysis.

Phipps said: “Chemical reactions that are driven by radical mechanisms are rapidly growing in importance, but it is an ongoing challenging to control enantioseletivity in those that form stereocentres. This grant will fund an ambitious program which will apply innovative and unexplored ion-pairing strategies to control enantioselectivity in a variety of important radical chemistries for which there are no or limited existing methods for imposing enantiocontrol.

“I am extremely grateful that my proposal was selected for funding in this very competitive call. I am excited about the chemistry that my group will be able to explore over the coming five years with this fantastic opportunity!”

Akshay Rao, Professor of Physics of the Cavendish Laboratory in the Department of Physics, has been awarded a grant for SPICE: Spin-Exchange and Energy Transfer at Hybrid Molecular/Lanthanide Nanoparticle Interfaces to Control Triplet Excitons.

Rao said: “Our project, SPICE, will explore the physics and chemistry of a new class of hybrid materials, organic molecules connected to lanthanide doped nanoparticles.

“Although we are still at an early stage of research, if we succeed it may create transformative applications in areas ranging from optoelectronics, data communication, photocatalysis, optogenetics and 3D bio-printing. Over the long term this kind of blue-sky science is what drives technological innovation helping to drive improved productivity in industry, but also directly tacking major societal challenges such as climate change and health.

“We are delighted that our project has received the support of the European Research Council. This is a great opportunity for us to pursue high-risk high-gain blue-sky science and push the limits of our understanding of these materials and take them towards application. ̽��ֱ��award also serves as recognition of the excellent science done by our PhD students and postdoctoral researchers, who’s tireless efforts to push the scientific frontier have made possible the breakthroughs that have brought us here.”

Dr Milka Sarris, Assistant Professor of the Department of Physiology, Development and Neuroscience, was awarded a grant for LongWayFromFlam: ̽��ֱ��uncharted journeys of inflammatory cells and their functional implications.

Sarris said: “My group studies how cells of the immune system move in the body to generate and resolve inflammatory responses. To study these processes, we use state of the art microscopy techniques and genetic approaches in zebrafish, a small vertebrate model organism.

“I am absolutely thrilled to have won this award at a key stage of my career and to be able to pursue an ambitious new line of fundamental research. It was a long process and I remain very grateful to my university colleagues, the peer reviewers and the evaluation committee for their feedback.”

Eight researchers from the ̽��ֱ�� of Cambridge have won European Research Council (ERC) Consolidator Grants

Photos provided by winners

From clockwise: Eloy de Lera Acedo, Daniel Hodson, Sohini Kar-Narayan, Elisa Laurenti, Naomi McGovern, Robert Phipps, Akshay Rao and Milka Sarris.

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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First ever clinical trial of lab-grown red blood cell transfusion

cjb250 — Mon, 07 Nov 2022 00:05:46 +0000

̽��ֱ��manufactured blood cells were grown from stem cells from donors. ̽��ֱ��red cells were then transfused into volunteers in the RESTORE randomised controlled clinical trial.

This is the first time in the world that red blood cells that have been grown in a laboratory have been given to another person as part of a trial into blood transfusion.

If proved safe and effective, manufactured blood cells could in time revolutionise treatments for people with blood disorders such as sickle cell and rare blood types. It can be difficult to find enough well-matched donated blood for some people with these disorders.

Chief Investigator Professor Cedric Ghevaert, Professor in Transfusion Medicine and Consultant Haematologist at the ̽��ֱ�� of Cambridge and NHS Blood and Transplant, said: “We hope our lab grown red blood cells will last longer than those that come from blood donors. If our trial, the first such in the world, is successful, it will mean that patients who currently require regular long-term blood transfusions will need fewer transfusions in future, helping transform their care.”

̽��ֱ��RESTORE trial is a joint research initiative by NHS Blood and Transplant and the ̽��ֱ�� of Bristol, working with the ̽��ֱ�� of Cambridge, Guy’s and St Thomas’ NHS Foundation Trust, NIHR Cambridge Clinical Research Facility, and Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust. It is part-funded by a National Institute for Health and Care Research (NIHR) grant.

Professor Ashley Toye, Professor of Cell Biology at the ̽��ֱ�� of Bristol and Director of the NIHR Blood and Transplant Unit in red cell products, said: “This challenging and exciting trial is a huge stepping stone for manufacturing blood from stem cells. This is the first-time lab grown blood from an allogeneic donor has been transfused and we are excited to see how well the cells perform at the end of the clinical trial.”

̽��ֱ��trial is studying the lifespan of the lab grown cells compared with infusions of standard red blood cells from the same donor. ̽��ֱ��lab-grown blood cells are all fresh, so the trial team expect them to perform better than a similar transfusion of standard donated red cells, which contains cells of varying ages.

Additionally, if manufactured cells last longer in the body, patients who regularly need blood may not need transfusions as often. That would reduce iron overload from frequent blood transfusions, which can lead to serious complications.

̽��ֱ��trial is the first step towards making lab grown red blood cells available as a future clinical product. For the foreseeable future, manufactured cells could only be used for a very small number of patients with very complex transfusions needs. NHSBT continues to rely on the generosity of donors.

Co-Chief Investigator Dr Rebecca Cardigan, Head of Component Development NHS Blood and Transplant and Affiliated Lecturer at the ̽��ֱ�� of Cambridge, said: “It’s really fantastic that we are now able to grow enough red cells to medical grade to allow this trial to commence. We are really looking forward to seeing the results and whether they perform better than standard red cells.”

Two people have so far been transfused with the lab grown red cells. They were closely monitored and no untoward side effects were reported. They are well and healthy. ̽��ֱ��identities of participants infused so far are not currently being released, to help keep the trial ‘blinded’.

̽��ֱ��amount of lab grown cells being infused varies but is around 5-10mls - about one to two teaspoons.

Donors were recruited from NHSBT’s blood donor base. They donated blood to the trial and stem cells were separated out from their blood. These stem cells were then grown to produce red blood cells in a laboratory at NHS Blood and Transplant’s Advanced Therapies Unit in Bristol. ̽��ֱ��recipients of the blood were recruited from healthy members of the NIHR BioResource.

A minimum of 10 participants will receive two mini transfusions at least four months apart, one of standard donated red cells and one of lab grown red cells, to find out if the young red blood cells made in the laboratory last longer than cells made in the body.

Further trials are needed before clinical use, but this research marks a significant step in using lab grown red blood cells to improve treatment for patients with rare blood types or people with complex transfusion needs.

John James OBE, Chief Executive of the Sickle Cell Society, said: “This research offers real hope for those difficult to transfuse sickle cell patients who have developed antibodies against most donor blood types. However, we should remember that the NHS still needs 250 blood donations every day to treat people with sickle cell and the figure is rising. ̽��ֱ��need for normal blood donations to provide the vast majority of blood transfusions will remain. We strongly encourage people with African and Caribbean heritage to keep registering as blood donors and start giving blood regularly.”

Dr Farrukh Shah, Medical Director of Transfusion for NHS Blood and Transplant, said: “Patients who need regular or intermittent blood transfusions may result develop antibodies against minor blood groups which makes it harder to find donor blood which can be transfused without the risk of a potentially life-threatening reaction. This world leading research lays the groundwork for the manufacture of red blood cells that can safely be used to transfuse people with disorders like sickle cell. ̽��ֱ��need for normal blood donations to provide the vast majority of blood will remain. But the potential for this work to benefit hard to transfuse patients is very significant.”

Adapted from a press release from NHS Blood and Transplant

Cambridge researchers are taking part in the world’s first clinical trial of red blood cells that have been grown in a laboratory for transfusion into another person.

If our trial is successful, it will mean that patients who currently require regular long-term blood transfusions will need fewer transfusions in future, helping transform their care

Cedric Ghevaert

First ever clinical trial of lab-grown red blood cell transfusion

NHS Blood and Transplant

Cell culture flasks in the incubator during manufacture of red blood cells

Yes

Cambridge researchers awarded European Research Council funding

Anonymous — Thu, 17 Mar 2022 13:14:45 +0000

Cambridge received the most awards of any UK institution, alongside ̽��ֱ�� College London, which also received five awards.

̽��ֱ��Cambridge winners are among 313 winners of the latest round of Consolidator Grants, backed with some €632 million. Part of the EU’s Horizon Europe programme, this new round of grants will create an estimated 1,900 jobs for postdoctoral fellows, PhD students and other staff at 189 host institutions.

Dr Ana Cvejic from the Department of Haematology was awarded a grant for her CONTEXT project (Aneuploidy and Its Impact on Blood Development: Context Matters). ̽��ֱ��focus of her research is to understand how blood cells develop and how their development and their ultimate function is influenced by their environment and environmental cues. ̽��ֱ��aim is to use this knowledge to develop new ways to treat disease and improve human health.

Professor Nikku Madhusudhan from the Institute of Astronomy was awarded a grant for his SUBNEPTUNES project (Probing Exoplanetary Atmospheres in the Sub-Neptune Regime). His research is focused on the atmospheres, interiors and formation mechanisms of exoplanets. In 2021, he identified a new class of exoplanet, dubbed Hycean planets, which could greatly accelerate the search for life outside our Solar System.

Professor Ulrich Schneider from the Cavendish Laboratory was awarded a grant for his KAGOME project (A quantum gas microscope for the Kagome lattice). Schenider studies ‘many-body’ phenomena at the interface between quantum optics and solid state physics.

Dr Philippa Steele from the Faculty of Classics was awarded a grant for her VIEWS project (Visual Interactions in Early Writing Systems). Her research focuses on the relationships between Aegean writing systesm and the development of the early Greek alphabet.

Dr Laura Torrente Murciano from the Department of Chemical Engineering and Biotechnology was awarded funding for her RESTARTNH3 project (Energy functional processes and materials for storage of renewable energy in ammonia). Her research focuses on the integration of processes and development of novel catalytic routes for sustainable technologies.

President of the ERC Professor Maria Leptin said: ”Even in times of crisis and conflict and suffering, it is our duty to keep science on track and give our brightest minds free reign to explore their ideas. We do not know today how their work might revolutionise tomorrow - we do know that they will open up new horizons, satisfy our curiosity and most likely help us prepare for unpredictable future challenges. So, I am thrilled to see a new group of ERC grant winners funded for their scientific journey. I wish them the best of luck on their way to push the frontiers of our knowledge!”

Five ̽��ֱ�� of Cambridge researchers have been awarded Consolidator Grants from the European Research Council, the premier European funding organisation for excellent frontier research.

Westend61

European Commission, Brussels

Yes

̽��ֱ��Academy of Medical Sciences announces election of new Fellows 2021

cg605 — Wed, 12 May 2021 09:39:48 +0000

̽��ֱ��Academy of Medical Sciences has elected 50 prominent biomedical and health scientists to its respected and influential Fellowship. ̽��ֱ��new Fellows have been selected for their exceptional contributions to the advancement of medical science through innovative research discoveries and translating scientific developments into benefits for patients and the wider society.

Professor Dame Anne Johnson, President of the Academy of Medical Sciences, said: “I am truly delighted to welcome these 50 new Fellows to the Academy’s Fellowship, and I offer my congratulations to each of them on their exceptional contribution to biomedical and health science. ̽��ֱ��knowledge, skill and influence that each brings to the Fellowship is the Academy’s most powerful asset.

“ ̽��ֱ��last year has clearly demonstrated the power and prowess of UK biomedical science, and I am proud of how many Fellows, new and old, have been at the forefront of the COVID-19 response in the UK and globally.

“Although it is hard to look beyond the pandemic right now, I want to stress how important it is that the Academy Fellowship represents the widest diversity of biomedical and health sciences. ̽��ֱ��greatest health advances rely on the findings of many types of research, and on multidisciplinary teams and cross-sector and global collaboration.”

Professor Franklin Aigbirhio FRSC

Professor of Molecular Imaging Chemistry, Department of Clinical Neurosciences and the Department of Chemistry, Senior Research Fellow, Magdalene College

Professor Aigbirhio’s research focuses on the development and application of new biomedical imaging technologies for clinical research in areas such as dementia, acute brain injury and hypertension. His research seeks to enable earlier detection and a greater understanding of the disorders, thereby aiding the development of new treatments. A further objective of Professor Aigbirhio’s work is to enable these new imaging technologies to be more accessible and widely applied throughout the NHS.

“It’s a pleasure and honour to be elected to this Fellowship, which I recognise is an outcome of the collaborations with many talented colleagues at Cambridge and further afield, for which I give my sincere thanks,” said Aigbirhio.

“Going forward my election to the Fellowship provides a platform to highlight the role of black researchers and participants in biomedical and health research and to increase their involvement.”

Professor Ravindra Gupta

Professor of Clinical Microbiology at the Cambridge Institute of Therapeutic Immunology and Infectious Diseases, Fellow, Homerton College

Professor Gupta has worked extensively in HIV, both at molecular and population levels, and his work demonstrating escalating global resistance led to change in WHO treatment guidelines for HIV. He led the team that demonstrated HIV cure in the ‘London Patient’ – only the second in history.

In 2020 he was named as one of the 100 most influential people worldwide by TIME Magazine. Gupta deployed his expertise in RNA virus genetics and biology during the COVID-19 pandemic to report the first evidence for immune escape of SARS-CoV-2 within an individual, defining the process by which new variants likely arise, and also reporting the first data on Pfizer BioNTech vaccine-induced antibody responses against the B.1.1.7 ‘Kent UK’ variant.

“I am honoured to have been elected to Fellowship of the Academy of Medical Sciences,” said Gupta. “ ̽��ֱ��COVID-19 pandemic has demonstrated the importance of cross-disciplinary science. Research excellence across medical sciences and translation to health improvements has been at the centre of the Academy’s mission and I am very pleased to now be able to contribute to fulfilling this aim as a Fellow.”

Professor Brian Huntly

Head of the Department of Haematology and Professor of Leukaemia Stem Cell Biology, Group Leader at the Wellcome – MRC Cambridge Stem Cell Institute

Professor Huntly’s research focuses on the stem cell aspects of the evolution of haematological malignancies, in particular acute myeloid leukaemia and lymphoma. His election recognises his many contributions to the understanding and treatment of blood cancers.

“I am delighted and honoured to be elected to the Fellowship of the Academy of Medical Sciences,” said Huntly. “ ̽��ֱ��Academy’s aims of bringing the best minds in biomedical research together, supporting talent, asking challenging questions and sharing our work so that all can benefit from it mirror very much our own aims here in Cambridge. Biomedical research is a hugely collaborative endeavour and I see my election as recognition of the hard work of many people who have contributed to my research and also highlighting the tremendous work we are doing at the ̽��ֱ�� of Cambridge Department of Haematology.”

Professor Adrian Liston

Senior Group Leader, Babraham Institute, Senior Research Fellow, Churchill College

Professor Adrian Liston works in the field of immunology, based around the question of the biological checkpoints that restrain immune activation. His research investigates the basis for pathological immune activation in the contexts of autoimmune diseases, primary immunodeficiencies and neuroinflammation. By understanding the genetic, molecular and cellular basis of immune checkpoint failure in these conditions, the rationale selection of therapeutics can help prevent or treat pathologies.

“This is a really wonderful recognition of the work from my team”, Liston said. “I’ve been lucky to work with an outstanding team of scientists, able to work on immune pathology from different angles – from the clinic or the lab, as an immunologist or a neuroscientist, in advanced techniques ranging from cytometry through to computational modelling. ̽��ֱ��curiosity and interdisciplinarity of the team are what has let us explore new fields and push the boundaries forwards.”

Professor Benjamin Simons FRS

Royal Society EP Abraham Professor, Department of Applied Mathematics and Theoretical Physics and Senior Group Leader of the Gurdon Institute, Group Leader at the Wellcome – MRC Cambridge Stem Cell Institute, Fellow, St John's College

As a theorist, Professor Simons has contributed to a diverse range of fields, from quantum condensed matter physics to developmental and cancer biology. His research translates concepts and approaches from statistical physics to gain predictive insights in the collective dynamics of complex systems. In biology, his studies have revealed common mechanisms of stem cell regulation, and how these programmes become subverted during the early phase of tumour growth.

Simons said: “As a theorist, and relative newcomer to the field of biomedical sciences, it is a great honour to be elected as a Fellow of the Academy of Medical Sciences.”

Cambridge scientists are among the new Fellows announced today by the Academy of Medical Sciences.

̽��ֱ��greatest health advances rely on the findings of many types of research, and on multidisciplinary teams and cross-sector and global collaboration.

Professor Dame Anne Johnson, President of the Academy of Medical Sciences

Yes