̽��ֱ�� of Cambridge - Cambridge Stem Cell Institute

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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Cambridge researchers named 2025 Schmidt Science Fellows

Anonymous — Mon, 07 Apr 2025 11:55:17 +0000

Now in its eighth year, the Fellowship provides financial support for a postdoctoral placement of one to two years at a world-class research institution.

̽��ֱ��funding equips scientists to apply their knowledge to a new field of study with the goal of accelerating discoveries, and to develop their leadership potential.

Dr Poppy Oldroyd, a 2025 Schmidt Science Fellow from the Department of Engineering, plans to pioneer a new frontier in understanding brain communication through optical measurements, ultimately advancing treatments for memory-related diseases.

̽��ֱ��human brain communicates through intricate networks of neurons, crucial for learning and memory. However, how these neural conversations translate into memory formation remains a mystery in neuroscience. Oldroyd’s research aims to use light-based tools, like advanced optogenetics, to explore these pathways in detail. By uncovering how specific brain circuits contribute to learning and memory, this research could revolutionise our understanding of these essential brain functions.

Ultimately, this knowledge may enhance our comprehension of memory-related disorders like Alzheimer’s disease and epilepsy.

Dr Matthew McLouglin, a 2025 Schmidt Science Fellow from the Cambridge Stem Cell Institute, plans to develop tools to study how our cells age in real time. This will help us understand why we age and how we might promote healthy aging to improve quality of life in the elderly.

Our DNA is organised into structures called chromosomes. Each chromosome has a protective cap, the ‘telomere’, which is partially lost with each cell division. In old age, cells cannot function properly due to the loss of telomeres, increasing the risk of age-related diseases such as cancer and dementia. McLoughlin will use cutting-edge imaging technology to track the loss of telomeres over time, understanding how telomeres are lost and why this stops cells from functioning.

Oldroyd and McLoughlin join a community of 209 Schmidt Science Fellows from nearly 40 countries who are leaders in interdisciplinary science.

“Philanthropic funding of scientific research, and especially support of early-career researchers, has never been more important,” said Wendy Schmidt, who co-founded Schmidt Science Fellows with her husband, Eric.

“By providing Schmidt Science Fellows with support, community, and freedom to work across disciplines and gain new insights, we hope they’ll tackle some of the world’s most vexing challenges, achieve breakthroughs and help create a healthier, more resilient world for all.”

Established in 2017, Schmidt Science Fellows is a programme of Schmidt Sciences delivered in partnership with the Rhodes Trust.

̽��ֱ��2025 Fellows represent 15 nationalities, including researchers from Jordan and the United Arab Emirates for the first time in the programme’s history.

This year’s cohort will work on a range of problems from cancer treatment to quantum technologies to sustainability.

Alongside their research Placement, Fellows participate in a 12-month interdisciplinary Science Leadership Programme.

Each year, Schmidt Science Fellows works in partnership with more than 100 universities to identify candidates for the Fellowship.

Nominees are selected via an application process that includes an academic review with panels of experts in their original disciplines and final interviews with a multidisciplinary panel of scientists and private sector leaders.

“ ̽��ֱ��Schmidt Science Fellows Program is cultivating a dynamic global community of remarkable scientists and champions of interdisciplinary research,” said Stu Feldman, Chief Scientist at Schmidt Sciences.

“Their work exemplifies Schmidt Sciences’ commitment to support pioneering approaches that will drive the next era of discovery and innovation.”

̽��ֱ��2025 Schmidt Science Fellows represent 27 nominating universities, including, for the first time, McGill ̽��ֱ�� in Canada, RWTH Aachen ̽��ֱ�� in Germany, Tecnológico de Monterrey in Mexico, ̽��ֱ�� of California, Los Angeles in the US, and ̽��ֱ�� of Groningen in the Netherlands.

Two ̽��ֱ�� of Cambridge researchers are among the thirty-two early career researchers, tackling issues from improving food security to developing better medical implants, who have been announced as the 2025 Schmidt Science Fellows.

Schmidt Science Fellows

Poppy Oldroyd (left) and Matthew McLoughlin (right)

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̽��ֱ��Cambridge Awards 2024 for Research Impact and Engagement

zs332 — Mon, 03 Feb 2025 10:27:01 +0000

Meet the winner of the Cambridge Awards 2024 for Research Impact and Engagement and learn more about their projects.

Cambridge researchers developing brain implants for treating Parkinson’s disease

sc604 — Thu, 23 Jan 2025 10:33:21 +0000

As part of a £69 million funding programme supported by the Advanced Research + Invention Agency (ARIA), Professor George Malliaras from Cambridge’s Department of Engineering will co-lead a project that uses small clusters of brain cells called midbrain organoids to develop a new type of brain implant, which will be tested in animal models of Parkinson’s disease.

̽��ֱ��project led by Malliaras and Professor Roger Barker from the Department of Clinical Neurosciences, which involves colleagues from the ̽��ֱ�� of Oxford, the ̽��ֱ�� of Lund and BIOS Health, is one of 18 projects funded by ARIA as part of its Precision Neurotechnologies programme, which is supporting research teams across academia, non-profit R&D organisations, and startups dedicated to advancing brain-computer interface technologies.

̽��ֱ��programme will direct £69 million over four years to unlock new methods for interfacing with the human brain at the neural circuit level, to treat many of the most complex neurological and neuropsychiatric disorders, from Alzheimer’s to epilepsy to depression.

By addressing bottlenecks in funding and the lack of precision offered by current approaches, the outputs of this programme will pave the way for addressing a much broader range of conditions than ever before, significantly reducing the social and economic impact of brain disorders across the UK.

Parkinson’s disease occurs when the brain cells that make dopamine (a chemical that helps control movement) die off, causing movement problems and other symptoms. Current treatments, like dopamine-based drugs, work well early on, but can cause serious side effects over time.

In the UK, 130,000 people have Parkinson’s disease, and it costs affected families about £16,000 per year on average – more than £2 billion in the UK annually. As more people age, the number of cases will grow, and new treatments are urgently needed.

One idea is to replace the lost dopamine cells by transplanting new ones into the brain. But these cells need to connect properly to the brain’s network to fix the problem, and current methods don’t fully achieve that.

In the ARIA-funded project, Malliaras and his colleagues are working on a new approach using small clusters of brain cells called midbrain organoids. These will be placed in the right part of the brain in an animal model of Parkinson’s disease. They’ll also use advanced materials and electrical stimulation to help the new cells connect and rebuild the damaged pathways.

“Our ultimate goal is to create precise brain therapies that can restore normal brain function in people with Parkinson’s,” said Malliaras.

“To date, there’s been little serious investment into methodologies that interface precisely with the human brain, beyond ‘brute force’ approaches or highly invasive implants,” said ARIA Programme Director Jacques Carolan. “We’re showing that it’s possible to develop elegant means of understanding, identifying, and treating many of the most complex and devastating brain disorders. Ultimately, this could deliver transformative impact for people with lived experiences of brain disorders.”

Other teams funded by the programme include one at Imperial College London who is developing an entirely new class of biohybridised technology focused on engineering transplanted neurons with bioelectric components. A Glasgow-led team will build advanced neural robots for closed-loop neuromodulation, specifically targeting epilepsy treatment, while London-based Navira will develop a technology for delivering gene therapies across the blood-brain barrier, a crucial step towards developing safer and more effective treatments.

Adapted from an ARIA media release.

Cambridge researchers are developing implants that could help repair the brain pathways damaged by Parkinson’s disease.

Our ultimate goal is to create precise brain therapies that can restore normal brain function in people with Parkinson’s

George Malliaras

Science Photo Library via Getty Images

Substantia nigra in the human brain, illustration

Yes

Cartographers of the human body: the Human Cell Atlas

cjb250 — Wed, 20 Nov 2024 16:00:45 +0000

̽��ֱ��Human Cell Atlas is an ambitious project to map every cell in the human body. Its co-lead, Professor Sarah Teichmann, explains how the initiative is already changing our understanding of our bodies.

Professor David Rowitch elected to US National Academy of Medicine

cjb250 — Mon, 21 Oct 2024 15:30:33 +0000

Election to the Academy is considered one of the highest honours in the fields of health and medicine and recognises individuals who have demonstrated outstanding professional achievement and commitment to service.

“It is a great honour to have been elected to the National Academy of Medicine,” said Professor Rowitch.

Professor Rowitch obtained his PhD from the ̽��ֱ�� of Cambridge. His research in the field of developmental neurobiology has focused on glial cells that comprise the ‘white matter’ of the human brain. It has furthered understanding human neonatal brain development as well as white matter injury in premature infants, multiple sclerosis and leukodystrophy. Amongst numerous awards, he was elected a Fellow of the Academy of Medical Sciences in 2018 and Fellow of the Royal Society in 2021.

Professor Rowitch’s current interest focuses on functional genomic technologies to better diagnose and treat rare neurogenetic disorders in children. He is academic lead for the new Cambridge Children’s Hospital, developing integrated paediatric physical-mental healthcare and research within the NHS and ̽��ֱ�� of Cambridge.

NAM President Victor J. Dzau said: “This class of new members represents the most exceptional researchers and leaders in health and medicine, who have made significant breakthroughs, led the response to major public health challenges, and advanced health equity.

“Their expertise will be necessary to supporting NAM’s work to address the pressing health and scientific challenges we face today. It is my privilege to welcome these esteemed individuals to the National Academy of Medicine.”

Professor Rowitch is one of 90 regular members and 10 international members announced during the Academy’s annual meeting. New members are elected by current members through a process that recognises individuals who have made major contributions to the advancement of the medical sciences, health care, and public health.

Professor David Rowitch, Head of the Department of Paediatrics at the ̽��ֱ�� of Cambridge, has been elected to the prestigious National Academy of Medicine in the USA.

Professor David Rowitch

Yes

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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