̽��ֱ�� of Cambridge - Elisa Laurenti

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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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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Vice-Chancellor’s awards recognise the difference researchers make to society

cjb250 — Thu, 13 Jul 2017 10:44:35 +0000

̽��ֱ��announcement was made at a prize ceremony held at the Old Schools on 13 July. At the same event, one of Cambridge’s leading experts on EU law – and in particular, Brexit – received one of the Vice Chancellor’s Public Engagement with Research Awards for her work around the EU Referendum.

Professor Sir Leszek Borysiewicz, Vice-Chancellor of the ̽��ֱ�� of Cambridge, says: “I would like to offer my warm congratulations to the recipients of our Impact and Public Engagement Awards. These are outstanding examples that reflect the tremendous efforts by our researchers to make a major contribution to society.”

Vice-Chancellor’s Impact Awards

̽��ֱ��Vice-Chancellor’s Impact Awards were established to recognise and reward those whose research has led to excellent impact beyond academia, whether on the economy, society, culture, public policy or services, health, the environment or quality of life. Each winner receives a prize of £1,000 and a trophy, with the overall winner - Dr Alexander Patto from the Department of Physics – receiving £2,000.

This year’s winners are:

Overall winner: Dr Alexander Patto (Department of Physics)

WaterScope

Using an open-source flexure microscope, spin-out company WaterScope is developing rapid, automated water testing kits and affordable diagnostics to empower developing communities. Its microscopes are being used for education, to inspire future scientists from India to Colombia. Its open-source microscope is supporting local initiatives, with companies such as STIClab in Tanzania making medical microscopes from recycled plastic bottles.

Elroy Dimson (Judge Business School)

‘Active Ownership’: Engaging with investee companies on environmental and social issues

‘Active Ownership’ refers to commitment by asset owners and their portfolio managers to engage with the businesses they own, focusing on issues that matter to all stakeholders and to the economy as a whole, including environmental, social and governance (ESG) concerns. By providing evidence to guide ESG strategy, Professor Dimson’s research has had a substantial impact on investment policy and practice.

Professor Nick Morrell (Department of Medicine)

From genetics to new treatments in pulmonary arterial hypertension

Severe high blood pressure in the lungs, known as idiopathic pulmonary arterial hypertension, is a rare disease that affects approximately 1,000 people in the UK. ̽��ֱ��condition usually affects young women and average life expectancy is three to five years. Existing treatments improve symptoms but have little impact on survival. Professor Morrell has introduced routine genetic testing for this condition, and found that one in four patients carry a particular genetic mutation associated with more severe disease and worse survival. His research has identified new ways to treat the disease, the most promising of which is being commercialised through a university spin-out biotech company.

Professor Lawrence Sherman, Peter Neyroud, Dr Barak Ariel, Dr Cristobal Weinborn and Eleanor Neyroud (Institute of Criminology)

Cambridge Crime Harm Index

̽��ֱ��Cambridge Crime Harm Index is a tool for creating a single metric for the seriousness of crime associated with any one offender, victim, address, community, or prevention strategy, supplementing traditional measures giving all crimes equal weight. ̽��ֱ��UK Office of National Statistics credits the index as the stimulus to institute its own, modified version from 2017. Police use the Cambridge index to target highest-harm offenders, victims, places, times and days, differences in crime harm per capita differs across communities or within them over time, adding precision to decisions for allocating scarce resources in times of budget cuts.

Vice-Chancellor’s Public Engagement with Research Awards

̽��ֱ��Vice-Chancellor’s Public Engagement with Research Awards were set up to recognise and reward those who undertake quality engagement with research. Each winner receives a £1000 personal cash prize and a trophy. This year’s winners are:

Professor Catherine Barnard (Faculty of Law)

In the run up to the EU membership referendum Professor Barnard developed a range of outputs to explain key issues at stake including migration, which forms the basis of her research, in addition to the wider EU law remit. Harnessing the timeliness of the political climate, Barnard’s videos, online articles, radio and TV interviews have supported her engagement across 12 town hall events from Exeter to Newcastle, an open prison and round-table discussions with various public groups. She has also provided a number of briefing sessions to major political party MPs and peers. She has become a trusted public figure, and researcher, on EU law, Brexit and surrounding issues, ensuring that the voices of those key to the research process are heard and listened to.

Dr Elisa Laurenti (Wellcome/MRC Stem Cell Institute and Department of Haematology)

Dr Laurenti has engaged over 2,500 people, at six separate events, with her Stem Cell Robots activity. She collaborated with a researcher in educational robotics to produce this robot-based activity, which maps a stem cell’s differentiation to become a specific cell type. ̽��ֱ��activity has provided a platform for children, families and adults to discuss ethics and clinical applications of stem cell research.

Dr Nai-Chieh Liu (Department of Veterinary Medicine)

Dr Liu has developed a non-invasive respiratory function test for short-skulled dog breeds, including French bulldogs and pugs, which suffer from airway obstruction. She has engaged with dog owners by attending dog shows, dog club meetings and breeders’ premises to break down barriers between publics and veterinarians working to improve the health of these dogs. As a result of this engagement, the UK French bulldog club and the Bulldog Breed Council have adopted health testing schemes based on Dr Liu’s research.

Dr Neil Stott and Belinda Bell (Cambridge Centre for Social Innovation, Judge Business School)

Dr Stott and Miss Bell established Cambridge Social Ventures to embed research around social innovation into a practical workshop to support emerging social entrepreneurs. Since the first workshop in 2014, they have reached almost 500 people wanting to create social change by starting and growing a business. ̽��ֱ��team goes to considerable efforts to reach out to participants from non-traditional backgrounds and to ensure workshops are inclusive and accessible to a wide range of people by incorporating online engagement with work in the community.

Amalia Thomas (Department of Applied Mathematics and Theoretical Physics)

Amalia Thomas researches photoelasticity, a property by which certain materials transmit light differently when subjected to a force. Amalia has developed an engaging exhibition for secondary school students comprising interactive elements, which uses photoelasticity to visualise force, work and power.

Dr Frank Waldron-Lynch, Jane Kennet and Katerina Anselmiova (Department of Medicine and Department of Clinical Biochemistry)

Since the commencement of their research programme to develop drugs for Type 1 Diabetes, Dr Waldron-Lynch, Ms Kennet and Ms Anselmiova have developed a public engagement programme to engage participants, patients, families, funders, colleagues, institutions, companies and the community, with the aim of ensuring that their research remains relevant to stakeholder needs. Amongst their outputs, the team has formed a patient support group in addition to developing an online engagement strategy through social media platforms. Most recently, they have collaborated with GlaxoSmithKline to offer patients the opportunity to participate in clinical studies at all stages of their disease.

An open source, 3D-printable microscope that forms the cornerstone of rapid, automated water testing kits for use in low and middle-income countries, has helped a Cambridge researcher and his not-for-profit spin-out company win the top prize in this year’s Vice-Chancellor’s Impact Awards at the ̽��ֱ�� of Cambridge.

Nithi Anand

I drink because I'm thirsty

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