Cellular plasticity and senescence at the origin of lung cancer
Lead Research Organisation:
University of Cambridge
Department Name: Oncology
Abstract
Cancer is a leading cause of morbidity and mortality worldwide. Every year some 15 million new cancer cases are diagnosed, and over 8 million people succumb annually to a variety of cancer types. Some 1.5 million of the former deaths are directly assigned to lung cancer, making it the most common cause of cancer-related fatality. Despite the remarkable efforts in lung cancer research of the last decades we yet ignore the underlying mechanisms promoting malignant transformation. Consequently, the available tools for lung cancer early diagnosis as well as the therapeutic approaches at hand are not good enough to tackle this disease. Most of the lung cancer cases escape diagnosis until they are at an advanced stage, which results in around 85% of patients having a 5-year mortality from first diagnosis.
Identification of the cell that initiates lung cancer is still a controversial issue and it remains unknown to what extent it determines tumour phenotype. It has been speculated that different lung tumour subtypes arise from distinct cells of origin localised in defined microenvironments. It has also been proposed that stem/progenitor cells may originate lung cancer due to their prolonged lifespan and capacity for self-renewal and differentiation. In the case of solid tumours like lung cancer, however, where the identification of cancer stem cells or progenitor cells relies on the expression of surface markers, it is unclear whether tumours follow a stochastic or a hierarchical growth. A satisfactory model(s) elucidating lung cancer initiation and tumour heterogeneity is thus yet to be verified. Evidence recently obtained in different tumour models, including glioblastomas, pancreatic and intestinal cancers, showed that the cell of origin is a differentiated cell that after exposition to diverse sources of damage undergoes de-differentiation and acquires a premalignant "plastic state" that initiates cancer. We will test in this proposal how cellular de-differentiation affects lung cancer initiation and progression in a microenvironment of damage and/or oncogenic stress.
Cellular senescence is a defence mechanism that occurs when a single cell is afflicted by different types of damage or stress, including oncogenic stress. Usually, these cells arrest and divide no more, and are subsequently eliminated by the immune system. Senescent cells accumulate in premalignant lesions, including lung adenomas, where senescence is a defining feature. Senescent cells can however implement in different tissues a complex secretory phenotype (termed SASP) that includes pro-inflammatory and pro-tumorigenic factors when they are accumulated and not cleared, which may in turn promote cancer. Based on our preliminary results, we hypothesize that senescent cells may produce through the SASP a maladaptive gain of plasticity in nearby differentiated cells favouring lung cancer initiation. In this regard, we have observed in mouse lungs a close association between senescent cells and cells expressing pluripotency markers upon damage or oncogenic stress. We will determine whether senescence-induced plasticity is a potent oncogenic promoter in the lung.
We will employ mouse models where lung cancer has been induced either genetically or chemically, strains to manipulate cellular senescence and to induce de-differentiation processes, and lineage tracing approaches. We will acquire supporting data in a clinical oncology context through the analysis of human lung tissue samples. The overall purpose of this project is to achieve a better understanding of the mechanisms and processes contributing to lung cancer initiation at the cellular level, still a formidable challenge in oncology. Such fundamental knowledge is crucial to develop more efficient diagnostic tools, especially for the early detection of lung cancer, and novel therapeutic interventions and treatment modalities, therefore meeting an already existing and demanding clinical need.
Identification of the cell that initiates lung cancer is still a controversial issue and it remains unknown to what extent it determines tumour phenotype. It has been speculated that different lung tumour subtypes arise from distinct cells of origin localised in defined microenvironments. It has also been proposed that stem/progenitor cells may originate lung cancer due to their prolonged lifespan and capacity for self-renewal and differentiation. In the case of solid tumours like lung cancer, however, where the identification of cancer stem cells or progenitor cells relies on the expression of surface markers, it is unclear whether tumours follow a stochastic or a hierarchical growth. A satisfactory model(s) elucidating lung cancer initiation and tumour heterogeneity is thus yet to be verified. Evidence recently obtained in different tumour models, including glioblastomas, pancreatic and intestinal cancers, showed that the cell of origin is a differentiated cell that after exposition to diverse sources of damage undergoes de-differentiation and acquires a premalignant "plastic state" that initiates cancer. We will test in this proposal how cellular de-differentiation affects lung cancer initiation and progression in a microenvironment of damage and/or oncogenic stress.
Cellular senescence is a defence mechanism that occurs when a single cell is afflicted by different types of damage or stress, including oncogenic stress. Usually, these cells arrest and divide no more, and are subsequently eliminated by the immune system. Senescent cells accumulate in premalignant lesions, including lung adenomas, where senescence is a defining feature. Senescent cells can however implement in different tissues a complex secretory phenotype (termed SASP) that includes pro-inflammatory and pro-tumorigenic factors when they are accumulated and not cleared, which may in turn promote cancer. Based on our preliminary results, we hypothesize that senescent cells may produce through the SASP a maladaptive gain of plasticity in nearby differentiated cells favouring lung cancer initiation. In this regard, we have observed in mouse lungs a close association between senescent cells and cells expressing pluripotency markers upon damage or oncogenic stress. We will determine whether senescence-induced plasticity is a potent oncogenic promoter in the lung.
We will employ mouse models where lung cancer has been induced either genetically or chemically, strains to manipulate cellular senescence and to induce de-differentiation processes, and lineage tracing approaches. We will acquire supporting data in a clinical oncology context through the analysis of human lung tissue samples. The overall purpose of this project is to achieve a better understanding of the mechanisms and processes contributing to lung cancer initiation at the cellular level, still a formidable challenge in oncology. Such fundamental knowledge is crucial to develop more efficient diagnostic tools, especially for the early detection of lung cancer, and novel therapeutic interventions and treatment modalities, therefore meeting an already existing and demanding clinical need.
Technical Summary
Our main objective is a better understanding of the mechanisms and processes that lay at the origin of lung cancer. In other tumour models, it is known that, upon damage and/or oncogenic stress, differentiated cells may undergo de-differentiation (gain of plasticity) acquiring malignant phenotypes. Since cell senescence is a response to damage and stress, and senescent cells can secrete pro-inflammatory and pro-tumorigenic factors, we hypothesize these cells can also induce in nearby cells de-differentiation processes favouring lung cancer initiation.
Our specific aims are:
(i) To induce lung de-differentiation processes upon damage (urethane treatment) and/or oncogenic stress (K-Ras activation). To do so, we will employ a regrogrammable mouse model transiently expressing the four Yamanaka factors. We will determine whether reprogramming-induced de-differentiation is an oncogenic promoter.
(ii) To capture early tumour cells expressing transiently or stably de-differentiation markers by using a lineage tracing mouse strain and FACS approaches. Cells will be subjected to RNAseq analyses and epigenetic techniques such as chromatin immunoprecipitation.
(iii) To address the interplay between cell senescence and de-differentiation processes during lung tumorigenesis. Senescence will be manipulated both genetically and chemically during lung cancer initiation. Lineage tracing approaches will allow us to perform longitudinal studies on the activation of pluripotency markers and how it relates to senescence. We will determine if senescence-induced plasticity is an important oncogenic promoter.
(iv) To identify factors secreted by senescent cells able to induce de-differentiation of nearby cells and/or malignant transformations. Microdissected sections of tumours from control and senescence-manipulated mice will be subjected to gene expression and protein arrays. Conditioned media from cultured senescent cells will be subjected to SILAC analyses.
Our specific aims are:
(i) To induce lung de-differentiation processes upon damage (urethane treatment) and/or oncogenic stress (K-Ras activation). To do so, we will employ a regrogrammable mouse model transiently expressing the four Yamanaka factors. We will determine whether reprogramming-induced de-differentiation is an oncogenic promoter.
(ii) To capture early tumour cells expressing transiently or stably de-differentiation markers by using a lineage tracing mouse strain and FACS approaches. Cells will be subjected to RNAseq analyses and epigenetic techniques such as chromatin immunoprecipitation.
(iii) To address the interplay between cell senescence and de-differentiation processes during lung tumorigenesis. Senescence will be manipulated both genetically and chemically during lung cancer initiation. Lineage tracing approaches will allow us to perform longitudinal studies on the activation of pluripotency markers and how it relates to senescence. We will determine if senescence-induced plasticity is an important oncogenic promoter.
(iv) To identify factors secreted by senescent cells able to induce de-differentiation of nearby cells and/or malignant transformations. Microdissected sections of tumours from control and senescence-manipulated mice will be subjected to gene expression and protein arrays. Conditioned media from cultured senescent cells will be subjected to SILAC analyses.
Planned Impact
The Pathways to Impact Assessment, the potential beneficiaries of this project on lung cancer are multiple and diverse reflecting the fact that it aims to deliver knowledge and know-how at three fundamental levels: molecular mechanisms, cell processes and pathological disorders.
Our expected advancements on the molecular front will be beneficial to:
- molecular biologists and cancer researchers, through the development of new techniques for the isolation of tumour precursor cells;
- oncologist consultants, which will have at hand a new tool to detect alterations during cancer initiation thanks to the characterisation of gene expression profiles and epigenetic changes of cancer precursor cells;
- drug discovery programmes, after the identification of new drugable targets in lung cancer initiation.
Our progress on better understanding the role of cellular senescence and gain of cellular plasticity processes will be very useful for cell biologists interested in cancer initiation, cell senescence and plasticity, stem/progenitor cells and cell reprogramming. Satisfactory results attained within this proposal may provide us with the grounds for the diversification of our own research towards the development of nanoparticles to specifically target senescent cells in lung premalignant lesions which in turn could eventually be of some use for translational researchers and engineers working in imaging and biomarker approaches.
On the pathological front, a better understanding of lung cancer initiation is crucial to develop novel tools for early detection the design of more efficient therapeutic interventions. In the former context Dr Robert Rintoul, Lung Cancer Lead Clinician at Papworth Hospital and Director of the Clinical Trials Unit, will directly benefit thanks to our already established collaboration. Given that senescence is associated with multiple cancers and premalignant lesions, the Cambridge Cancer Centre will directly benefit from our proposal. This includes Prof Sir Bruce Ponder, former director of the CRUK Cambridge Institute, through an ongoing collaboration. Cell senescence also operates in a multitude of chronic pathologies making our proposal thus of interest to a broader research community operating in basic and translational projects both in the UK and overseas.
Our expected advancements on the molecular front will be beneficial to:
- molecular biologists and cancer researchers, through the development of new techniques for the isolation of tumour precursor cells;
- oncologist consultants, which will have at hand a new tool to detect alterations during cancer initiation thanks to the characterisation of gene expression profiles and epigenetic changes of cancer precursor cells;
- drug discovery programmes, after the identification of new drugable targets in lung cancer initiation.
Our progress on better understanding the role of cellular senescence and gain of cellular plasticity processes will be very useful for cell biologists interested in cancer initiation, cell senescence and plasticity, stem/progenitor cells and cell reprogramming. Satisfactory results attained within this proposal may provide us with the grounds for the diversification of our own research towards the development of nanoparticles to specifically target senescent cells in lung premalignant lesions which in turn could eventually be of some use for translational researchers and engineers working in imaging and biomarker approaches.
On the pathological front, a better understanding of lung cancer initiation is crucial to develop novel tools for early detection the design of more efficient therapeutic interventions. In the former context Dr Robert Rintoul, Lung Cancer Lead Clinician at Papworth Hospital and Director of the Clinical Trials Unit, will directly benefit thanks to our already established collaboration. Given that senescence is associated with multiple cancers and premalignant lesions, the Cambridge Cancer Centre will directly benefit from our proposal. This includes Prof Sir Bruce Ponder, former director of the CRUK Cambridge Institute, through an ongoing collaboration. Cell senescence also operates in a multitude of chronic pathologies making our proposal thus of interest to a broader research community operating in basic and translational projects both in the UK and overseas.
Organisations
- University of Cambridge (Lead Research Organisation)
- QUEEN MARY UNIVERSITY OF LONDON (Collaboration)
- Polytechnic University of Valencia (Collaboration)
- Galician Healthcare Service (Collaboration)
- Wellcome Trust (Collaboration)
- Spanish National Cancer Research Center (Collaboration)
- CAMBRIDGE UNIVERSITY HOSPITALS NHS FOUNDATION TRUST (Collaboration)
- Institute for Research in Biomedicine (IRB) (Collaboration)
- UNIVERSITY OF CAMBRIDGE (Collaboration)
- ROYAL PAPWORTH HOSPITAL NHS FOUNDATION TRUST (Collaboration)
People |
ORCID iD |
| Daniel Munoz-Espin (Principal Investigator) |
Publications
Baixauli-Martín J
(2022)
Brain Cell Senescence: A New Therapeutic Target for the Acute Treatment of Ischemic Stroke.
in Journal of neuropathology and experimental neurology
Barbouti A
(2019)
In situ evidence of cellular senescence in Thymic Epithelial Cells (TECs) during human thymic involution.
in Mechanisms of ageing and development
Bermúdez-Muñoz JM
(2021)
Dual-Specificity Phosphatase 1 (DUSP1) Has a Central Role in Redox Homeostasis and Inflammation in the Mouse Cochlea.
in Antioxidants (Basel, Switzerland)
Denholm M
(2022)
SARS-CoV-2-induced senescence as a potential therapeutic target.
in The European respiratory journal
Gonzalez-Gualda E
(2022)
Cellular senescence in non-small cell lung cancer: from mechanisms to therapeutic opportunities
Gonzalez-Gualda E
(2022)
A tumour-promoting senescent secretome triggered by platinum chemotherapy exploits a targetable TGFßR1/Akt-mTOR axis in lung cancer
in bioRxiv
González-Gualda E
(2020)
Galacto-conjugation of Navitoclax as an efficient strategy to increase senolytic specificity and reduce platelet toxicity.
in Aging cell
González-Gualda E
(2021)
A guide to assessing cellular senescence in vitro and in vivo.
in The FEBS journal
Haston S
(2023)
Clearance of senescent macrophages ameliorates tumorigenesis in KRAS-driven lung cancer
in Cancer Cell
Lozano-Torres B
(2021)
A Two-Photon Probe Based on Naphthalimide-Styrene Fluorophore for the In Vivo Tracking of Cellular Senescence.
in Analytical chemistry
| Description | CRUK Cambridge Centre Early Detection Interest Groups Launch - Biomarkers and Tumour Microenvironment |
| Geographic Reach | Local/Municipal/Regional |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Impact | The interest groups will create a community with shared research interests, who will form new collaborations with a view to accelerating research and generating further opportunity for strong funding applications. Following these introductory pitches, there will be the opportunity for participants to follow up in greater detail with those colleagues whose research is of interest and has collaborative potential with their own. |
| URL | https://www.earlydetectioncambridge.org.uk/news-events/events/?range=upcoming&category=&location=&or... |
| Description | CRUK Cambridge Centre Early Detection Interest Groups Launch - Imaging and Devices |
| Geographic Reach | Local/Municipal/Regional |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Impact | The interest groups will create a community with shared research interests, who will form new collaborations with a view to accelerating research and generating further opportunity for strong funding applications. Following these introductory pitches, there will be the opportunity for participants to follow up in greater detail with those colleagues whose research is of interest and has collaborative potential with their own. |
| URL | https://www.earlycancer.cam.ac.uk/events |
| Description | Cambridge Philosophical Society Membership Lecture |
| Geographic Reach | Local/Municipal/Regional |
| Policy Influence Type | Membership of a guideline committee |
| Impact | Global and UK populations are rapidly ageing, resulting in dramatic increases in the incidence and prevalence of age-related disorders. The major impact of this lecture was to describe how the development of novel therapies to ameliorate the progression of these pathologies, including cancer, and promote "healthy" ageing in humans. The outcomes of our project are expected to add significantly to current knowledge at three fundamental levels: molecular (elucidating mechanisms) and cellular (elucidating processes); drug discovery and pathological impact (ageing and cancer). |
| URL | https://www.cambridgephilosophicalsociety.org/events/event/targeting-cellular-senescence-in-cancer-a... |
| Description | Cambridge Science Festival - CRUK Cambridge Centre Early Detection Programme - How early detected cancer lesions can be treated |
| Geographic Reach | Local/Municipal/Regional |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Impact | The Science Festival provides the public with opportunities to explore and discuss issues of scientific interest and concern and to raise aspirations by encouraging young people to consider a career in science, technology, engineering or mathematics. Each year, the Festival welcomes visitors to hundreds of events and receives extensive national and local media coverage. Over 170 event coordinators organise talks, interactive demonstrations, hands-on activities, film showings and debates with the assistance of around 1,000 staff and students from departments and organisations across the University and research institutions, charities and industry in the eastern region. In addition, over 150 people volunteer their time to act as stewards to ensure visitors have a safe and enjoyable Festival experience. |
| URL | https://cambridgesciencefestival.org |
| Description | International Summer School - Organisation of a Networking Activity as Scrum Master |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Impact | International Summer School Date: Monday 15th July 2019 - Thursday 18th July 2019 Venue: Robinson College, Grange Road, Cambridge CB3 9AN, UK We organised the first international summer school on discovery and development of diagnostics for the early detection of cancer. The summer school was aimed at those who are developing new technologies and interventions for the early detection of cancer and those who are interested in exploring this rapidly expanding and exciting field and was open to academic, corporate and student delegates. In July 2020 the inaugural International Early Detection Summer School, supported by the CRUK Cambridge Centre Early Detection Programme and the International Cancer Early Detection (ICED) Alliance, was held in the beautiful surroundings of Robinson College, Cambridge. The major theme of 'Discovery and Development of Diagnostics for Early Detection of Cancer' was delivered by world-class international Faculty, and the diagnostic development themes were explored more deeply in small groups through an interactive Team Activity. This was a truly international summer school with 60 delegates attending from 32 different institutions across 7 countries, including attendees from other ICED Alliance member centres, such as University of Manchester and UCL. The international faculty and speakers consisted of world leaders from a diverse range of specialities, including regulatory authorities, international certification bodies, large and small biotechnology companies, and academics focussed on cancer early detection. Delegates from the inaugural International Early Detection Summer School listening to the introductory talk from Prof Rebecca Fitzgerald, on the need for Cancer Early Detection and a case study of the CytoSpongeTM platform for oesophageal neoplasms, moderated by Dr Sarah Bohndiek (co-leader of the CCC Early Detection Programme). The Summer School provided insights from experts with real-world experience in developing diagnostics and key insights on the pathway to implementation. The speakers covered topics ranging from the need for cancer early detection and emerging technologies, to case-studies and clinical trials from successful pioneers in the field of Early Detection, including regulation and policy challenges of new screening and diagnostic tools. Talks from Rebecca Fitzgerald (CytospongeTM), Nickolas Papadopoulos (CancerSEEK), Barry Berger (Cologuard®), Henrik Winther (IMMray TM), and Attilla Lorincz (Qiagen/Digene HPV test) were among the success stories that covered development from concept to clinical trials and considerations for implementation of cancer early detection in a variety of malignancies. Stephen Quake (Stanford) and Chris Contag (Michigan State) covered exciting new technologies for cancer detection, ranging from molecular analysis to optical imaging. While real-world impact and implementation was covered from a broad range of perspectives by Anne Mackie (Public Health England), Maroeska Rovers (Radboud), Alberto Gutierrez (former FDA Director), Sian Taylor-Phillips (Warwick) and Robyn Meurant (NSF International). Considerations for the design of clinical trials and early detection of cancer in primary care were expertly covered by Peter Sasieni (King's College London) and Fiona Walter (Cambridge/CanTest). The balanced programme concluded with a final session of speakers covering the specific challenges for development in this area, both from a regulatory perspective and considerations for the societal impact of cancer early detection. Talks from Lynette Reid (Dalhousie), Stephen John (Cambridge) and Maryon McDonald (Cambridge), actively moderated by Stuart Hogarth (Cambridge), one of the co-organisers of the Summer School, gave much food for thought on the potential impacts of early detection and the importance of clarity in communicating with target 'testing' populations, as well as the need to ensure that any new early detection test strikes the correct balance between benefits and harms, to realise the core goal of 'timely detection' of lethal cancers to improve survival rates. Throughout the four-day Summer School five delegates trained by Carl Yamashiro (Arizona State University), including Wendy Alderton, Charlie Massie and Daniel Munoz-Espin (CCC Early Detection Programme), Valerie Sills (PHPC, Cambridge), and Cindy Azevedo (Arizona State University), took part in a team activity to work through the stages of developing an early detection test. Working in small groups after each session, delegates covered in greater depth the development process starting from concept and ideation, through considerations for specific technologies, practicalities for implementation, quality systems, assessing competition and IP, regulation, reimbursement, marketing, and final commercialisation. Using a tailored agile development programme, implemented together with the team from Arizona State University, delegates were mentored through the complexities and considerations for realising cancer early detection diagnostics. The team development activity culminated in a series of short presentations at the end of the Summer School and the award of the first International Early Detection Prizes! Team activity session. Working in small groups, delegates explored the key considerations for the development of cancer early detection tests. Using an agile development process and short 'sprints', facilitated by 'scrum masters' (in this case, Daniel Munoz-Espin). The feedback for the event was very positive, with 100% of delegates agreeing that the course was well organised and met the key objectives for the topics of Developing Diagnostics for Cancer Early Detection. We had very positive feedback from delegates: "Amazing range and level of speakers" "Cytosponge, CancerSEEK, Quake, Immunovia, Cologard were amazing talks. Learned a lot about science, regulatory, clinical validation, societal elements" "Excellent range of talks, great presenters across the board" "It was a really good multidisciplinary event and I enjoyed having the opportunity to network with researchers that are tackling the early detection problem form such different viewpoints." In conclusion, the first International Early Detection Summer School brought together an outstanding team of senior faculty, speakers, associates, and delegates from multiple international institutions sharing the vision of increasing survival from cancer and improving quality of life through early detection and intervention. We are already planning the next International Early Detection Summer School, so watch this space and look out for email alerts to make sure you don't miss out on the next Summer School! |
| URL | https://www.earlydetectioncambridge.org.uk/news-events/international-summer-school |
| Description | Lectures on Cancer Biology at University of Cambridge |
| Geographic Reach | Local/Municipal/Regional |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Impact | I gave an Online Lecture for the training of PhD students entitled "Targeting cellular senescence in cancer and ageing" on 18th June 2020. It was aimed at reinforcing the training and educational development for postgraduates. |
| URL | https://crukcambridgecentre.org.uk/content/lectures-cancer-biology-and-medicine |
| Description | Lectures on Cancer Biology at University of Cambridge |
| Geographic Reach | Local/Municipal/Regional |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Impact | I gave a Lecture for the training of PhD students entitled "Imaging techniques and novel tools for cancer early detection and intervention" on the 8th March 2018 at 9.30 am in Lecture Theatre 2 of the Clinical School, University of Cambridge. It was aimed at reinforcing the training and educational developments for postgraduates. |
| URL | https://crukcambridgecentre.org.uk/content/lectures-cancer-biology-and-medicine-2017-18 |
| Description | Lectures on Cancer Biology at University of Cambridge |
| Geographic Reach | National |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Impact | I gave an Online Lecture for the training of PhD students entitled "Targeting Cellular Senescence in Cancer and Ageing", July 2021. It was aimed at reinforcing the training and educational development for graduates. |
| URL | https://crukcambridgecentre.org.uk/content/lectures-cancer-biology-and-medicine |
| Description | Member of the CRUK Cambridge Centre Early Detection Programme Steering Committee |
| Geographic Reach | National |
| Policy Influence Type | Membership of a guideline committee |
| Impact | The International Alliance for Cancer Early Detection (ACED) is a science-led, collaborative investment that will support the early detection of cancer research. Launched in 2019, representing up to £55 million of investment over 5 years, this initiative brings together outstanding UK and US Centres to foster collaboration (University of Cambridge, Manchester University, UCL, OHSU and Canary Foundation), infrastructure development and training across the Alliance and for the wider early detection research community. ACED in Cambridge Led by Professor Rebecca Fitzgerald, the Cambridge ACED member centre is leveraging the success of its Early Detection Programme to bring world-class facilities and early detection expertise to the wider Alliance. Central to this is the development of ACED Clinic Cambridge, which will provide Alliance members with the resources and infrastructure required to conduct first-in-human clinical testing of novel diagnostics and imaging devices. We are dedicated to training, development and multidisciplinary collaboration: we hosted the first International ACED Summer School in 2019, are funding three PhD studentships and are actively supporting the development of collaborations across the Alliance. Click here for details on the next ACED Summer School. |
| URL | https://www.earlydetectioncambridge.org.uk/about/people/steering-committee |
| Description | Steering Committee Member of the International Cellular Senescence Association (ICSA) |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Participation in a guidance/advisory committee |
| URL | https://www.cellsenescence.info |
| Description | Cambridge Trust International Scholarship |
| Amount | £43,659 (GBP) |
| Organisation | Cambridge Commonwealth Trust |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 10/2018 |
| End | 09/2021 |
| Description | Dissecting the role of the senescent secretome in tumorigenesis. CRUK-OHSU Early Detection Project Award. |
| Amount | £250,000 (GBP) |
| Funding ID | C62187/A26989 |
| Organisation | Cancer Research UK |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 01/2019 |
| End | 12/2020 |
| Description | La Caixa Foundation Fellowship |
| Amount | £31,200 (GBP) |
| Organisation | La Caixa Banking Foundation |
| Sector | Private |
| Country | Spain |
| Start | 10/2017 |
| End | 09/2019 |
| Description | Marie Curie Fellowship - David Macias Gutierrez |
| Amount | € 118,220 (EUR) |
| Organisation | Marie Curie |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 01/2022 |
| End | 12/2023 |
| Description | Royal Society Research Grants |
| Amount | £15,000 (GBP) |
| Funding ID | RDAG/435 |
| Organisation | The Royal Society |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 03/2017 |
| End | 02/2018 |
| Title | Construction of vectors to generate novel mouse models to lineage trace senescent (p16-positive and p21-positive) cells |
| Description | Generation of mouse p16 and p21 gene targeting vectors to generate mouse models to lineage trace senescent (p16-positive and p21-positive) cells: P16 Donor Vector: P16 5'arm-IRES-frt-STOP-frt-mKATE2-2A-CreERT2-loxP-hPGK-blasticidin-loxP-3'arm P21 Donor Vector: P21 5'arm-IRES-frt-STOP-frt-mKATE2-2A-CreERT2-loxP-hPGK-blasticidin-loxP-3'arm |
| Type Of Material | Model of mechanisms or symptoms - mammalian in vivo |
| Year Produced | 2019 |
| Provided To Others? | No |
| Impact | Not yet, in progression. |
| Title | Galacto-Conjugated Navitoclax (Nav-Gal). This is a new prodrug with senolytic activity based on ABT-263, also known as navitoclax, (Eurodiagnostico) |
| Description | For the synthesis of Nav-Gal prodrug, 40 mg (0.04 mmol) of navitoclax (Eurodiagnostico), 25 mg (0.06 mmol) of 2,3,4,6-tetra-O-acetyl-a-D-galactopyranosyl-bromide (Sigma), and 10.5 mg (0.07 mmol) of K2CO3 (Sigma) were mixed. Anhydrous acetonitrile (Sigma) was added and the mixture was stirred at 70ºC for 3 h under argon-enriched atmosphere. The solvent was eliminated under vacuum. The product was purified by flash chromatography on silica gel (Sigma), from hexane-ethylacetate (3:7 v/v; Scharlab) to hexane-ethylacetate (7:3 v/v) used as eluent. Purified Nav-Gal was obtained as a yellow powder in 35% yield. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2020 |
| Provided To Others? | Yes |
| Impact | Article published in Aging Cell (2020) Gonzalez-Gualda E, Paez-Ribes M, Lozano-Torres B, Macias D, Wilson III JR, Gonzalez-Lopez C, Ou H-L, Miron-Barroso S, Zhang Z, Lerida-Viso A, Blandez JF, Bernardos A, Sancenon F, Rovira M, Fruk L, Martins CP, Serrano M, Doherty GJ, Martinez-Manez R, Muñoz-Espín D*. Galacto-conjugation of Navitoclax as an efficient strategy to increase senolytic specificity and reduce platelet toxicity. Aging Cell. 2020 9(4):e13142. doi: 10.1111/acel.13142. Epub 2020 Mar 31. |
| URL | https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13142 |
| Title | Galacto-Conjugated Navitoclax. |
| Description | We have developed and validated a novel prodrug with broad-sprectrum senolytic activity, namely Galacto-conjugated Navitoclax (Gal-Nav). Gal-Nav allows a therapeutically-relevant activity in combination with senescence-inducing chemotherapy (e.g Palbociclib and Cisplatin) in different in vivo models of cancer: (i) Orthotopically transplanted murine lung adenocarcinoma cells and (ii) tumour xenograft models of human Non Small Cell Lung Cancer (NSCLC). Our in vitro and in vivo results show that concomitant treatment of senogenic chemotherapies and senolytics significantly improve the therapeutic outcomes of the monotherapies alone and results in reduced toxicities. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2020 |
| Provided To Others? | Yes |
| Impact | Targeting cellular senescence is emerging as a novel and promising therapeutic strategy for many diseases. Our work demonstrates the following three points: • We describe and validate the use of galacto-conjugated navitoclax as a prodrug with broad-spectrum senolytic activity in a variety of cellular models. • Galacto-conjugated navitoclax allows therapeutically-relevant activity in combination with senescence-inducing chemotherapy (cisplatin) in two in vivo models of lung carcinogenesis: Orthotopically transplanted murine lung adenocarcinoma cells and in a tumour xenograft model of human NSCLC. • Importantly, galacto-conjugation has the important advantage of reducing navitoclax-induced platelet apoptosis (thrombocytopenia), which limits the use of BCL-2 inhibitors in the clinic (currently in clinical trials). We regard this as a major technical advance with potential wide therapeutic applications in medicine. |
| Title | Lentiviral plasmid LV-PGK-Akaluc-2A-Cre-2A-Venus-WPRE |
| Description | This new lentiviral construct will allow us to visualise and sort lung cells expressing oncogenic Kras (Venus fluorescence), to initiate lung cancer (CRE recombinase-dependent) and monitor tumour progression by IVIS imaging (Akaluc luciferase activity dependent). This new lentiviral construct can be adapted to other models of carcinogenesis or disease. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2022 |
| Provided To Others? | No |
| Impact | This tool will be useful for our preclinical research with mouse models and published in a research article in proper time. |
| Title | Naphthalimide-styrene-based probe (HeckGal) for the detection of cellular senescence both in vitro and in vivo |
| Description | The HeckGal probe consists of a naphthalimide-styrene fluorophore covalently linked to an acetylated ß-galactose through the anomeric carbon. HeckGal is poorly emissive, whereas a sudden revival of the emission is observed in the presence of senescence-associated lysosomal ß-Gal activity. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| Impact | A Two-Photon Probe Based on Naphthalimide-Styrene Fluorophore for the In Vivo Tracking of Cellular Senescence Beatriz Lozano-Torres, Juan F Blandez, Irene Galiana, José A Lopez-Dominguez, Miguel Rovira, Marta Paez-Ribes, Estela González-Gualda, Daniel Muñoz-Espín, Manuel Serrano, Félix Sancenón*, and Ramón Martínez-Máñez* Anal. Chem. 2021, 93, 5, 3052-3060 |
| URL | https://pubs.acs.org/doi/10.1021/acs.analchem.0c05447 |
| Title | p16FDR mice |
| Description | This is a new Knock In model allowing the visualisation, isolation, lineage tracing and ablation of p16-positive cells. It contains a Flipase Recombinase-Diphteria Toxin Receptor-mCherry cassette cloned downstream of the exon 3 of the Cdkn2a gene. We have validated the use of this mouse in the context of oncogene-induced senescence in Kras-driven lung cancer. |
| Type Of Material | Model of mechanisms or symptoms - mammalian in vivo |
| Year Produced | 2022 |
| Provided To Others? | No |
| Impact | We are preparing the generated data for the submission of a research article. |
| Title | p16FDR mice that allows for the visualisation, isolation, genetic tracing and pharmacogenetic ablation of Cdkn2a (p16INK4a)-expressing senescent cells in vivo |
| Description | We have generated a novel knock-in mouse model, termed p16-FDR, and demonstrated its potential to identify, isolate, ablate and trace p16INK4a-expressing cells in vivo. We have utilised this new tool to uncover novel insights into the cell type identity and role of senescent cells during lung tumourigenesis. In addition, we confirm the accumulation of p16INK4a-expressing cells within multiple tissues during ageing, reveal the existence of multiple distinct senescent cell types and identify commonalities between aged and tumourigenic lungs. |
| Type Of Material | Model of mechanisms or symptoms - mammalian in vivo |
| Year Produced | 2021 |
| Provided To Others? | No |
| Impact | These data are submitted for publication. This work has been done in a collaboration between the laboratories of Dr Juan Pedro Martinez-Barbera (UCL), Prof Jesus Gil (Imperial College) and Daniel Munoz-Espin (University of Cambridge). Title: A new mouse model reveals heterogeneity of Cdkn2a (p16INK4a)- expressing cells during lung tumourigenesis and ageing |
| Title | p16mKC and p21mKC mice |
| Description | Generation of transgenic knock-in mice to visualise, lineage trace, isolate and ablate p16- and p21-expressing cells. p16mKC: p16 5'arm-IRES-frt-STOP-frt-mKATE2-2A-CreERT2-loxP-hPGK-blasticidin-loxP-3' p21mKC: p21 5'arm-IRES-frt-STOP-frt-mKATE2-2A-CreERT2-loxP-hPGK-blasticidin-loxP-3' |
| Type Of Material | Model of mechanisms or symptoms - mammalian in vivo |
| Year Produced | 2021 |
| Provided To Others? | No |
| Impact | We are in the process of characterising these new mouse models. |
| Title | Gene expression (RNAseq) and proteomics (MEMA) profiles of therapy-induced senescent cells and lung cancer cells |
| Description | Platinum-based chemotherapeutic regimens are standard treatments for non-small cell lung cancer (NSCLC) patients, but long-term clinical outcomes remain poor. Cellular senescence and its associated secretory phenotype (SASP) can have multiple tumour-promoting activities, although these are largely unexplored in lung cancer. To gain insight into the gene expression profiles occurring upon chemotherapy-driven senescence, we performed RNA-seq analyses of control, cisplatin-, docetaxel- and palbociclib-induced senescent A549 and KP L1475luc cells. To identify distinctive proinflammatory (SASP) factors potentially driving increased proliferation in recipient A549 cells, we used a microenvironment microarray (MEMA) platform. This recent technology allows the screening of the functional effects of multiple combinations of individual factors and cytokines in an unbiased high-throughput manner and the subsequent analysis of treated cell read-outs through advanced imaging |
| Type Of Material | Database/Collection of data |
| Year Produced | 2022 |
| Provided To Others? | Yes |
| Impact | The data have been published in bioRxiv, in a public repository. The bulk RNAseq dataset generated to support the findings of this study are available in the EMBL's European Bioinformatics Institute (EBI) database: European Nucleotide Archive (ENA) repository, Accession Number PRJEB52271 (https://www.ebi.ac.uk/ena/browser/home). A549 MEMA data is available on Synapse (https://www.synapse.or) (ID: syn27665118). All other data supporting the findings of this study are available from the corresponding author upon request. The bulk RNAseq data were aligned using STAR (v2.6.1d) (59). Quality control was carried out with STAR (v2.6.1d) (59) and samtools (v1.9) (60, 61). Read counts extracted with FeatureCounts (v1.6.4) (62). Normalisation of read counts for analysis was carried out by EdgeR (63-65) and Limma (66) within R environment (v3.0.6). Pathway analyses was performed in KEGG (KEGGREST version 1.24.1) (67), GO (GOSEQ version 1.36.0) (68) and GSEA (FGSEA version 1.10.1) (69-71) R packages. The A549 MEMA custom code is available on GitHub (https://github.com/markdane/A549_low_serum). RNA-seq raw data are available in the EBI database. European Nucleotide Archive (ENA) repository Accession Number PRJEB52271, and code used for data analyses are available upon request. Any additional information required to reanalyse the data reported in this work paper is available from the Lead contact upon request. |
| URL | https://www.biorxiv.org/content/10.1101/2022.08.01.502019v1 |
| Title | Gene expression profiles (RNAseq) of lung cancer cells (A549 and L1475) expressing the 4 Yamanaka (OSKM) factors |
| Description | We have performed whole transcriptome shotgun sequencing (RNAseq) to analyse lung cancer cells (A549 and L1475) expressing the 4 Yamanaka (OSKM) factors. This has allowed us to investigate the interplay between pluripotency and cancer and identify novel vulnerabilities in lung cancer cells. Databases will be shared at the time our results are submitted to a peer-reviewed research journal for publication, and also in international conferences. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2021 |
| Provided To Others? | No |
| Impact | We are currently using these data for the preparation of a research article. |
| Title | Gene expression profiles (RNAseq) of lung cancer cells conditionally expressing the 4 Yamanaka factors |
| Description | We have performed whole transcriptome shotgun sequencing (RNAseq) to analyse mouse lung cancer cells expressing the 4 Yamanaka factors (L1475luc-OSKM) in a doxycycline dependent-manner ). These data will be further completed by using models of in vivo reprogramming, which may provide information on how cellular plasticity and pluripotency impacts cancer progression. Databases will be shared at the time our results are submitted to a peer-reviewed research journal for publication, and also in international conferences. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2020 |
| Provided To Others? | No |
| Impact | These results are being used for the preparation of a research article. |
| Title | Gene expression profiles (RNAseq) of senescent cells and lung cancer cells |
| Description | We have performed whole transcriptome shotgun sequencing (RNAseq) to analyse human lung cancer cells (A549) undergoing different types of therapy-induced senescence (cisplatin, docetaxel and palbociclib-based). In addition, we have analysed the transcriptome of recipient human lung cancer cells (A549) exposed to different senescent secretomes. This will allow us to have a better understanding of the pro-tumorigenic (or pro-senescent) effects of the senescent secretome. These data will be further completed by using models of oncogene-induced senescence, which may represent more accurately the early phases of lung carcinogenesis, and by developing 3D cultures based on organoids. Databases will be shared at the time our results are submitted to a peer-reviewed research journal for publication, and also in international conferences. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2019 |
| Provided To Others? | No |
| Impact | The development of tumour organoids in our laboratory may be a good replacement method allowing us to reduce the numbers of mice. We are currently setting up this novel approach in collaboration with Dr Joo-Hyeon Lee (WT Cambridge Stem Cell Institute). |
| Title | Gene expression profiles (RNAseq) of therapy-induced senescent cells and lung cancer cells |
| Description | We have performed whole transcriptome shotgun sequencing (RNAseq) to analyse human lung cancer cells (A549) undergoing different types of therapy-induced senescence (cisplatin, docetaxel and palbociclib-based). In addition, we have analysed the transcriptome of recipient human lung cancer cells (A549) exposed to different senescent secretomes at different time points. This will allow us to have a better understanding of the pro-tumorigenic (or pro-senescent) effects of the senescent secretome. Databases will be shared at the time our results are submitted to a peer-reviewed research journal for publication, and also in international conferences. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2020 |
| Provided To Others? | No |
| Impact | We are currently using these data for the preparation of a research article. |
| Title | Gene expression profiles (RNAseq) of therapy-induced senescent cells and lung cancer cells |
| Description | We have performed whole transcriptome shotgun sequencing (RNAseq) to analyse mouse lung cancer KPcells (L1475) undergoing therapy-induced senescence (cisplatin-induced). In addition, we have analysed the transcriptome of recipient mouse lung cancer KPcells (L1475) exposed to cisplatin-induced senescent secretomes. This allewed us to have a better understanding of the pro-tumorigenic effects of the senescent secretome. Databases will be shared at the time our results are submitted to a peer-reviewed research journal for publication, and also in international conferences. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2021 |
| Provided To Others? | No |
| Impact | We are in the process to submit these data for a peer-reviewed journal. |
| Title | Human Tissues Samples |
| Description | Collection of human tissue samples of lung tumours, lung fibrosis and other pulmonary pathologies |
| Type Of Material | Database/Collection of data |
| Year Produced | 2019 |
| Provided To Others? | No |
| Impact | The histological analysis of human tissue samples were used in a collaboration with Dr Ana O'Loghlen (Blizard Institute, London): Borghesan et al. Cell Reports 2019. |
| URL | https://www.sciencedirect.com/science/article/pii/S221112471930734X?via%3Dihub |
| Title | Old p16FDR mice (scRNAseq data) |
| Description | This is a new Knock In model allowing the visualisation, isolation, lineage tracing and ablation of p16-positive cells. It contains a Flipase Recombinase-Diphteria Toxin Receptor-mCherry cassette cloned downstream of the exon 3 of the Cdkn2a gene. We have validated the use of this mouse in the context of oncogene-induced senescence in young and aged (2 years old) mice transplanted orthotopically with KP L1475 lung cancer cells. We have sorted mCherry (p16-positive) cells and mCherry negative populations of cells to perform scRNAseq data in the context of tumorigenesis. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2023 |
| Provided To Others? | No |
| Impact | Deciphering transcriptomic profiles of cells of the tumour microenvironment in young and naturally-aged mice and their role in lung cancer initiation and progression |
| Title | Proteomics Analyses of Cell Membrane Proteins in Chemotherapy-Treated Lung Cancer Cells |
| Description | We are screening surface membrane proteins that are specifically or preferentially expressed in senescent cells with the aim of identifying senescence targetable biomarkers. The proteins that we are studying were identified in an initial proteomics analysis in collaboration with Prof Paul Lehner (CMIR, University of Cambridge). We will first confirm the overexpression of the identified protein/s in senescent cells, and study the effects of inhibiting or manipulating the protein expression. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2019 |
| Provided To Others? | No |
| Impact | We performed a proteomic TMT-based analysis of cisplatin-induced senescent lung cancer cells in order to elucidate differences in the expression of proteins between senescent cells and their control counterparts. We conducted the biotinylation of proteins, biochemically labeling and protein separation of membrane and intracellular compartments, and performed a mass spectrometry screening. Preliminary analysis of the results shows differences on the protein levels and types between senescence and control cells. Due to the absence of universal biomarkers of senescent cells, the identification of cell surface (targetable) biomarkers is crucial for the development of novel and more specific senolytic, senomorphic and detection tools for senescent cells. There is a huge excitement with this field because of the recent realisation that cellular senescence is causative in multiple diseases in humans (reviewed in Muñoz-Espín D & Serrano M, Nat Rev Mol Cell Biol 2014), and hence senescent cells are an emerging target of a wide variety of age-related disorders (reviewed in Pérez-Mancera PA et al., Nat Rev Cancer 2014; Childs BG et al., Nat Rev Drug Disc 2017; Soto-Gamez et al., Drug Discovery Today 2017; Ovadya Y & Krizhanovsky V, JCI 2017; Gonzalez-Meljem JM et al., BJC 2018). Importantly, the elimination of senescent cells by genetic and pharmacological agents results in an increased healthspan and lifespan in mice (Baker DJ et al., Nature 2016; Xu M et al., Nat Med 2018). Even more, eradication of senescent cells not only ameliorates the pathological manifestations but, also, in some cases reverts the disease progression and contributes to tissue regeneration. Therefore, the development of novel tools to manipulate cellular senescence has an enormous potential in multiple clinical applications. |
| Title | Proteomics profiles of the therapy-induced senescence secretome (SASP) in lung cancer |
| Description | Protein Profiling by nanoLC/MS of A549 NSCLC cells implementing therapy-induced senescence by cisplatin, docetaxel and palbocicilb exposure. To analyse the different senescent secretomes the conditioned media of these cells was analysed. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2020 |
| Provided To Others? | No |
| Impact | These results are being used for the preparation of a research article. |
| Title | p16FDR mice-RNAseq and scRNAseq Data |
| Description | This is a new Knock In model allowing the visualisation, isolation, lineage tracing and ablation of p16-positive cells. It contains a Flipase Recombinase-Diphteria Toxin Receptor-mCherry cassette cloned downstream of the exon 3 of the Cdkn2a gene. We have validated the use of this mouse in the context of oncogene-induced senescence in Kras-driven lung cancer and also DEN-induced esophageal cancer. We have sorted mCherry (p16-positive cells) to perform RNAseq and scRNAseq data. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2021 |
| Provided To Others? | No |
| Impact | We are preparing a manuscript to be submitted for publication. |
| Title | p16FDR mice-scRNAseq data |
| Description | This is a new Knock In model allowing the visualisation, isolation, lineage tracing and ablation of p16-positive cells. It contains a Flipase Recombinase-Diphteria Toxin Receptor-mCherry cassette cloned downstream of the exon 3 of the Cdkn2a gene. We have validated the use of this mouse in the context of oncogene-induced senescence in Kras-driven lung cancer and also DEN-induced esophageal cancer. We have sorted mCherry (p16-positive cells) to perform scRNAseq data in the context of tumorigenesis. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2022 |
| Provided To Others? | Yes |
| Impact | Deciphering transcriptomic profiles of cells of the tumour microenvironment (mainly macrophages and endothelial cells) and their role in lung cancer initiation and progression. |
| Description | Cellular senescence and mouse models |
| Organisation | Institute for Research in Biomedicine (IRB) |
| Country | Spain |
| Sector | Academic/University |
| PI Contribution | We provide expertise in the role of cellular senescence in lung disorders, including lung cancer and pulmonary fibrosis. We also facilitate access to data related to the senescent secretome and transcriptomics analyses. |
| Collaborator Contribution | Prof Manuel Serrano provides expertise on cellular senescence and reprogramming, intellectual input, and provision of some relevant mouse models, including: - p53KO and p16ArfKO mice. - Reprogrammable mouse (OSKM inducible, expressing the 4 Yamanaka factors in a transient manner). |
| Impact | Recent publication of a Research Article: Muñoz-Espín D*, Rovira M, Galiana I, Giménez C, Lozano-Torres B, Paez-Ribes M, Llanos S, Chaib S, Muñoz M, Ucero AC, Garaulet G, Mulero F, Dann S, VanArsdale T, Shields DJ, Bernardos A, Murguía JR, Martínez-Máñez R, Serrano M*. A versatile drug delivery system targeting senescent cells. EMBO Mol Med. 2018; 10:e9355. (* Corresponding authors) doi: 10.15252/emmm.201809355. Patent: European Application Number: EP17382901.1. Title: Therapeutic Nanoparticles. Applicant: Spanish National Cancer Research Centre and Polytechnic University of Valencia. Inventors: Manuel Serrano, Daniel Muñoz, Miguel Rovira, Andrea Bernardos, Irene Galiana, Beatriz Lozano, Ramón Martínez, Félix Sanceón |
| Start Year | 2018 |
| Description | Clinical oversight |
| Organisation | Cambridge University Hospitals NHS Foundation Trust |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | We contribute our expertise in cellular senescence and mouse models of lung carcinogenesis |
| Collaborator Contribution | Dr Gary J Doherty (Oncologist and Respiratory Consultant) provides additional programme oversight and clinical lead in lung oncology. |
| Impact | Experimental designs of preclinical studies in order to have relevance in clinical settings. |
| Start Year | 2019 |
| Description | Consortium on Cellular Senescence - H2020-MSCA-ITN-2020-ENIGMAS |
| Organisation | Queen Mary University of London |
| Department | Blizard Institute |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | This is an European Network of Innovative Groups for research into the mechanisms of aging. The Consortium involves: 1. Queen Mary University of London. (Dr Cleo Bishop). 2. University of Cambridge. (Prof Masashi Narita). 3. Technische Universitaet Dresden (Germany). (Dr Maximina Yun). 4. Elvesys. (Dr Jessica Ayache, Dr Julia Sepulveda). 5. Universitaetsmedizin Göttingen (Germany). (Prof Argyris Papantonis). 6. Academisch Ziekenhuis Groningen (The Netherlands). (Dr Marco Demaria). 7. Institute for Research in Biomedicine, Barcelona (Spain). (Prof Manuel Serrano). 8. Ethnic Idryma Erevnon. (Dr Efstathios Gonos). 9. Institut Pasteur. (Dr Han Li). 10. Senolytic Therapeutics SL. (Dr Tim Cash). 11. Weizmann Institute of Science. (Dr Valery Krizhanovsky). |
| Collaborator Contribution | Targeted clearance of senescent cells offers a new landscape through which to tackle the increasing fiscal and societal burden related to our growing ageing population, and a fresh approach to address the H2020 Societal Challenges of healthy ageing. However, fundamental challenges must be over come to realise the potential of senotherapies. We need: - new strategies for detecting and dissecting senescence mechanisms at the single-cell level; - an understanding of the temporal dynamics of senescence cell accumulation and the consequences of senescent cell elimination in disease; - and proof-of-concept therapeutic tools to detect and target senescent cells. In response to these overarching EU needs, we have built ENIGMAS (European Network of Innovative Groups for research into the Mechanisms of Ageing and Senescence). We are a network of leading senescence groups united with industrial and commercial stakeholders to create a multidisciplinary, cross-sectoral and transnational network to address the urgent training needs within the field. Our mission is to train the first breed of dedicated Senescence and Ageing experts equipped with a unique blend of transferable and entrepreneurial expertise. Our proposed training platform links senescence, ageing and diseases of ageing with core skills (cell and molecular biology, in vitro and in vivo models, start-of-the-art imaging) and key emerging transformative techniques (single cell genomics, proteomics, tissue engineering) and transformative technologies (nanotechnology using our patented nanoparticle delivery system and innovative microfluidics) to develop a new generation of senescence experts that can think and communicate across disciplines and sectors. Throughout the training programme, our ESRs will work at the cutting-edge of inter-sectoral technology transfer with preclinical application and future commercialisation potential. |
| Impact | For the moment, we are at an initial stage of collaboration and have applied for H2020-MSCA-ITN-2020 (Marie Sklowdoska-Curie Innovative Training Networks). Proposal Acronym: ENIGMAS |
| Start Year | 2019 |
| Description | Department of Chemical Engineering and Biotechnology - University of Cambridge |
| Organisation | University of Cambridge |
| Department | Department of Chemical Engineering and Biotechnology |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We contribute our expertise in cellular senescence and cancer biology. We provide in vitro and in vivo models of lung cancer. |
| Collaborator Contribution | Dr Ljiljana Fruk (Department of Chemical Engineering and Biotechnology - University of Cambridge) provides expertise in the design, synthesis and validation of novel nanotechnologies and small molecules to target senescent and cancer cells. |
| Impact | Development of novel senoprobes to target senescent cells. We published recently a joint review as co-corresponding authors describing the most common hallmarks of senescence. |
| Start Year | 2018 |
| Description | Generation of mouse models for lineage tracing in lung carcinogenesis and tumour organoids |
| Organisation | Wellcome Trust |
| Department | Wellcome - MRC Cambridge Stem Cell Institute |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We contribute the construction of a vector to generate a novel mouse model for lineage tracing of p16-positive cells and another one for lineage tracing of p21-positive cells. |
| Collaborator Contribution | Dr Joo-Hyeon Lee provides her expertise in lineage tracing, stem cells, and generation of lung tumour organoids. |
| Impact | Future generation of novel mouse models for lineage tracing in lung carcinogenesis and novel tools based on tumour organoids. |
| Start Year | 2018 |
| Description | Human lung tissue samples |
| Organisation | Royal Papworth Hospital NHS Foundation Trust |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | We contribute our expertise in cellular senescence and mouse models of lung carcinogenesis |
| Collaborator Contribution | Dr Robert Rintoul (Respiratory Consultant) provides programme oversight and clinical lead in lung oncology. Dr Doris Rassl (Pathologist) provides the laboratory with human lung tissue samples and histology analysis. |
| Impact | Validation of results obtained in mouse models of lung carcinogenesis with human tissue samples. |
| Start Year | 2018 |
| Description | Lung cancer and mouse models |
| Organisation | Spanish National Cancer Research Center |
| Country | Spain |
| Sector | Public |
| PI Contribution | We provide expertise on the role of cellular senescence in lung carcinogenesis. |
| Collaborator Contribution | Prof Mariano Barbacid provides expertise on lung cancer and provision of mouse models: - FSF-KrasG12V - LSL-KrasG12VBgeo |
| Impact | Generation of novel in vivo models to study lung carcinogenesis. |
| Start Year | 2018 |
| Description | Nanotechnology - Polytechnic University of Valencia, Spain. |
| Organisation | Polytechnic University of Valencia |
| Country | Spain |
| Sector | Academic/University |
| PI Contribution | We contribute our expertise in cellular senescence and cancer biology. |
| Collaborator Contribution | Prof Ramon Martinez-Manez (Polytechnic University of Valencia and Scientific Director of CIBER-BBN) provides expertise in the design and synthesis of nanoparticles and senoprobes targeting senescent cells. |
| Impact | We have contributed a licence patent to Senolytics Therapeutics SL (EP17382901.1.) and several articles together, including: 1. Gonzalez-Gualda E, Paez-Ribes M, Lozano-Torres B, Macias D, Wilson III JR, Gonzalez-Lopez C, Ou H-L, Miron-Barroso S, Zhang Z, Lerida-Viso A, Blandez JF, Bernardos A, Sancenon F, Rovira M, Fruk L, Martins CP, Serrano M, Doherty GJ, Martinez-Manez R, Muñoz-Espín D*. Galacto-conjugation of Navitoclax as an efficient strategy to increase senolytic specificity and reduce platelet toxicity. Aging Cell. 2020 9(4):e13142. doi: 10.1111/acel.13142. Epub 2020 Mar 31. 2. Muñoz-Espín D*, Rovira M, Galiana I, Giménez C, Lozano-Torres B, Paez-Ribes M, Llanos S, Chaib S, Muñoz M, Ucero AC, Garaulet G, Mulero F, Dann S, VanArsdale T, Shields DJ, Bernardos A, Murguía JR, Martínez-Máñez R, Serrano M*. A versatile drug delivery system targeting senescent cells. EMBO Mol Med. 2018; 10:e9355. (* Corresponding authors). 3. Lozano-Torres B, Galiana I, Rovira M, Garrido E, Chaib S, Bernardos A, Muñoz-Espín D, Serrano M, Martínez-Máñez R, Sancenón F. An ON-OFF two-photon fluorescent probe to track cell senescence in vivo. J Am Chem Soc. 2017; 139:8808-11. 4. Beatriz Lozano-Torres, Juan F Blandez, Irene Galiana, José A Lopez-Dominguez, Miguel Rovira, MartaPaez-Ribes,EstelaGonzalez-Gualda,DanielMuñoz-Espín,ManuelSerrano,FelixSancenon,* and Ramon Martínez-Man ~ez*. A Two-Photon Probe Based on Naphthalimide-Styrene Fluorophore for the In Vivo Tracking of Cellular Senescence. Anal. Chem. 2021, 93, 3052-3060. |
| Start Year | 2018 |
| Description | Reprogramming and cellular plasticity |
| Organisation | Galician Healthcare Service |
| Country | Spain |
| Sector | Hospitals |
| PI Contribution | We contribute our expertise in cellular plasticity in lung carcinogenesis |
| Collaborator Contribution | Dr Manuel Collado provides expertise in cellular reprogramming and cancer stemness. He is also an expert in cellular senescence. |
| Impact | We have complementary models for lung carcinogenesis and reprogramming. We are designing multiple experiments in parallel and thinking in a future joint publication as a result of our strong interconnection. |
| Start Year | 2019 |
| Description | Role of cellular senescence in oesophageal cancer |
| Organisation | University of Cambridge |
| Department | Cambridge Stem Cell Institute |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We are providing our expertise in cellular senescence and also p16FDR mice, allowing the visualisation, isolation and ablation of p16-positive senescent cells in DEN-induced oesophageal cancer in mice. |
| Collaborator Contribution | Dr María Alcolea is collaborating with our laboratory in order to explore the incidence, role and impact of cellular senescence in DEN-induced oesophageal cancer by using murine models of carcinogenesis. Her laboratory is performing IF histological analyses and scRNAseq high-throughput analyses. |
| Impact | Preliminary data on the role of cellular senescence in early oesophageal carcinogenesis. Histological and scRNAseq data. |
| Start Year | 2021 |
| Description | ACED-Allience Cancer Early Detection - PitchFest 2020 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | International Festival of Ideas for the International Alliance Cancer Early Detection (ACED). Invited for a presentation as a speaker by Dr Nicole Lyons (ACED Programme Manager, CRUK) |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://www.cancerresearchuk.org/funding-for-researchers/research-opportunities-in-early-detection-a... |
| Description | AZ Partners of Choice Workshop |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | Explore potential synergistic opportunities between University of Cambridge and AZ. |
| Year(s) Of Engagement Activity | 2021 |
| Description | Annual Early Detection Symposium at CRUK Cambridge Institute 2019- Poster Presentation - Estela Gonzalez-Gualda |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Postgraduate students |
| Results and Impact | Poster presentation on the effects of chemotherapy-induced senescence in lung cancer progression. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.earlydetectioncambridge.org.uk/news-events/news/cruk-cambridge-centre-early-detection-pr... |
| Description | Annual Early Detection Symposium at CRUK Cambridge Institute 2020- Poster Presentation - Zhenguang Zhang |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Postgraduate students |
| Results and Impact | Poster presentation on the interplay between cellular reprogramming and lung cancer. |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://www.earlydetectioncambridge.org.uk/news-events/events/early-detection-programme-5th-annual-s... |
| Description | Annual Early Detection Symposium at CRUK Cambridge Institute 2021 - Oral Presentation - Estela Gonzalez |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | Oral presentation on the application of senolytics as potential cancer preventative therapies. |
| Year(s) Of Engagement Activity | 2021 |
| URL | https://www.earlydetectioncambridge.org.uk/news-events/events/early-detection-programme-sixth-annual... |
| Description | Annual Early Detection Symposium at CRUK Cambridge Institute 2021 - Poster Presentation - Cristina Gonzalez |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Postgraduate students |
| Results and Impact | Poster presentation on the identification of novel targetable biomarkers of the senescent surfaceome in cancer. |
| Year(s) Of Engagement Activity | 2021 |
| URL | https://www.earlydetectioncambridge.org.uk/news-events/events/early-detection-programme-sixth-annual... |
| Description | Biological theories for rejuvenation |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | About 300 respiratory consultants attended a debate on lung disease and ageing (invited by Dr Alvar Agusti. Neumochiesi 8th Edition. Real Fabrica de Tapices, Madrid, Spain). I gave a talk on biological theories for rejuvenation and participated in an open discussion. |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://www.actasanitaria.com/wp-content/uploads/2018/10/Programa-cient%C3%ADfico-Neumochiesi-2018.p... |
| Description | Biological theories for rejuvenation - CHIESI RESPIRATORY SYMPOSIUM |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | About 350 respiratory consultants attended a debate on lung disease and ageing (invited by Dr Julio Delgado. ESPACIO ASMA 8th Edition. Hotel Melia Alicante, Alicante, Spain. I gave a talk on biological theories for rejuvenation and participated in an open discussion. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.alicantecongresos.com/es/node/383 |
| Description | CRUK Cambridge Centre - Cancer Biology Lecture |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Postgraduate students |
| Results and Impact | Cancer Biology Lecture at CRUK Cambridge Centre for postgraduate students. Part of the training programme of the School of Clinical Medicine. |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://crukcambridgecentre.org.uk/content/lectures-cancer-biology-and-medicine |
| Description | CRUK Engagement Event in Chelmsford (UK) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Supporters |
| Results and Impact | Almost 100 people, including supporters, charitable donors, and general public attended an engagement event organised by CRUK (Dr Helen Dowding, Research Engagement Manager) and the Cambridge Cancer Centre Early Detection Programme. As part of the the Early Detection Programme, my colleagues and I presented some talks on early cancer biology and novel tools for early detection in the Essex Country Cricket Club (Chelmsford, UK). |
| Year(s) Of Engagement Activity | 2018 |
| Description | CRUK International Symposium at CRUK Cambridge Institute "Radical Approaches to Cancer Prevention"- Poster Presentation - Estela Gonzalez-Gualda |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Poster presentation on the impact of chemotherapy-induced senescence in lung cancer progression. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.immunology.cam.ac.uk/immunologycinferences/NonCINEvents/cruk-cambridge-institute-interna... |
| Description | CRUK/Abcam CC Workshop |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | Exploring synergistic opportunities between University of Cambridge, CRUK and Abcam. |
| Year(s) Of Engagement Activity | 2021 |
| Description | Cambridge Science Festival - CRUK Cambridge Centre Early Detection Programme |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | The Science Festival provides the public with opportunities to explore and discuss issues of scientific interest and concern and to raise aspirations by encouraging young people to consider a career in science, technology, engineering or mathematics. Each year, the Festival welcomes visitors to hundreds of events and receives extensive national and local media coverage. Over 170 event coordinators organise talks, interactive demonstrations, hands-on activities, film showings and debates with the assistance of around 1,000 staff and students from departments and organisations across the University and research institutions, charities and industry in the eastern region. In addition, over 150 people volunteer their time to act as stewards to ensure visitors have a safe and enjoyable Festival experience. We prepared an activity on the Early Detection of Lung Cancer, consisting in a video game that we created to target precancerous cells, a pinball with "drug-delivery balls" to target tumours, and an activity with a model of the human lung to detect early lesions by fluorescence techniques. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.sciencefestival.cam.ac.uk |
| Description | Canceropole GSO Annual Congress-Carcassone |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Invited speaker by the Canceropole GSO Committee and Dr David Santamaria. |
| Year(s) Of Engagement Activity | 2021 |
| URL | http://www.canceropole-gso.org/page/jgso2021/736-scientific-program.html |
| Description | Early Detection Cancer Conference |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | I was invited to give an oral presentation on my research by the ED Cancer Conference Committee. This annual event brings together experts in early detection from multiple disciplines to share ground breaking research and progress in the field. |
| Year(s) Of Engagement Activity | 2021 |
| URL | https://www.earlydetectioncambridge.org.uk/news-events/events/the-early-detection-of-cancer-conferen... |
| Description | Hitachi-University of Cambridge Bio Symposium |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Fusion of biology and digital technologies for 2050. This biosymposium was aimed at forging a strong multidisciplanary network between University of Cambridge and HITACHI. |
| Year(s) Of Engagement Activity | 2021 |
| Description | International Cellular Senescence Association (ICSA) Conference in Athens 2019 - Poster Presentation - Estela Gonzalez-Gualda |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Undergraduate students |
| Results and Impact | Presentation of a poster on the impact of chemotherapy-induced senescence in lung cancer progression. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.icsa2019-athens.gr |
| Description | International Cellular Senescence Association Meeting 2021-Osaka |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Invited speaker by the ICSA Scientific Committee. |
| Year(s) Of Engagement Activity | 2021 |
| Description | International Summer School - Organisation of a Networking Activity as Scrum Master |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | International Summer School Date: Monday 15th July 2019 - Thursday 18th July 2019 Venue: Robinson College, Grange Road, Cambridge CB3 9AN, UK We organised the first international summer school on discovery and development of diagnostics for the early detection of cancer. The summer school was aimed at those who are developing new technologies and interventions for the early detection of cancer and those who are interested in exploring this rapidly expanding and exciting field and was open to academic, corporate and student delegates. In July 2020 the inaugural International Early Detection Summer School, supported by the CRUK Cambridge Centre Early Detection Programme and the International Cancer Early Detection (ICED) Alliance, was held in the beautiful surroundings of Robinson College, Cambridge. The major theme of 'Discovery and Development of Diagnostics for Early Detection of Cancer' was delivered by world-class international Faculty, and the diagnostic development themes were explored more deeply in small groups through an interactive Team Activity. This was a truly international summer school with 60 delegates attending from 32 different institutions across 7 countries, including attendees from other ICED Alliance member centres, such as University of Manchester and UCL. The international faculty and speakers consisted of world leaders from a diverse range of specialities, including regulatory authorities, international certification bodies, large and small biotechnology companies, and academics focussed on cancer early detection. Delegates from the inaugural International Early Detection Summer School listening to the introductory talk from Prof Rebecca Fitzgerald, on the need for Cancer Early Detection and a case study of the CytoSpongeTM platform for oesophageal neoplasms, moderated by Dr Sarah Bohndiek (co-leader of the CCC Early Detection Programme). The Summer School provided insights from experts with real-world experience in developing diagnostics and key insights on the pathway to implementation. The speakers covered topics ranging from the need for cancer early detection and emerging technologies, to case-studies and clinical trials from successful pioneers in the field of Early Detection, including regulation and policy challenges of new screening and diagnostic tools. Talks from Rebecca Fitzgerald (CytospongeTM), Nickolas Papadopoulos (CancerSEEK), Barry Berger (Cologuard®), Henrik Winther (IMMray TM), and Attilla Lorincz (Qiagen/Digene HPV test) were among the success stories that covered development from concept to clinical trials and considerations for implementation of cancer early detection in a variety of malignancies. Stephen Quake (Stanford) and Chris Contag (Michigan State) covered exciting new technologies for cancer detection, ranging from molecular analysis to optical imaging. While real-world impact and implementation was covered from a broad range of perspectives by Anne Mackie (Public Health England), Maroeska Rovers (Radboud), Alberto Gutierrez (former FDA Director), Sian Taylor-Phillips (Warwick) and Robyn Meurant (NSF International). Considerations for the design of clinical trials and early detection of cancer in primary care were expertly covered by Peter Sasieni (King's College London) and Fiona Walter (Cambridge/CanTest). The balanced programme concluded with a final session of speakers covering the specific challenges for development in this area, both from a regulatory perspective and considerations for the societal impact of cancer early detection. Talks from Lynette Reid (Dalhousie), Stephen John (Cambridge) and Maryon McDonald (Cambridge), actively moderated by Stuart Hogarth (Cambridge), one of the co-organisers of the Summer School, gave much food for thought on the potential impacts of early detection and the importance of clarity in communicating with target 'testing' populations, as well as the need to ensure that any new early detection test strikes the correct balance between benefits and harms, to realise the core goal of 'timely detection' of lethal cancers to improve survival rates. Throughout the four-day Summer School five delegates trained by Carl Yamashiro (Arizona State University), including Wendy Alderton, Charlie Massie and Daniel Munoz-Espin (CCC Early Detection Programme), Valerie Sills (PHPC, Cambridge), and Cindy Azevedo (Arizona State University), took part in a team activity to work through the stages of developing an early detection test. Working in small groups after each session, delegates covered in greater depth the development process starting from concept and ideation, through considerations for specific technologies, practicalities for implementation, quality systems, assessing competition and IP, regulation, reimbursement, marketing, and final commercialisation. Using a tailored agile development programme, implemented together with the team from Arizona State University, delegates were mentored through the complexities and considerations for realising cancer early detection diagnostics. The team development activity culminated in a series of short presentations at the end of the Summer School and the award of the first International Early Detection Prizes! Team activity session. Working in small groups, delegates explored the key considerations for the development of cancer early detection tests. Using an agile development process and short 'sprints', facilitated by 'scrum masters' (in this case, Daniel Munoz-Espin). The feedback for the event was very positive, with 100% of delegates agreeing that the course was well organised and met the key objectives for the topics of Developing Diagnostics for Cancer Early Detection. We had very positive feedback from delegates: "Amazing range and level of speakers" "Cytosponge, CancerSEEK, Quake, Immunovia, Cologard were amazing talks. Learned a lot about science, regulatory, clinical validation, societal elements" "Excellent range of talks, great presenters across the board" "It was a really good multidisciplinary event and I enjoyed having the opportunity to network with researchers that are tackling the early detection problem form such different viewpoints." In conclusion, the first International Early Detection Summer School brought together an outstanding team of senior faculty, speakers, associates, and delegates from multiple international institutions sharing the vision of increasing survival from cancer and improving quality of life through early detection and intervention. We are already planning the next International Early Detection Summer School, so watch this space and look out for email alerts to make sure you don't miss out on the next Summer School! |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.earlydetectioncambridge.org.uk/news-events/news/successful-first-international-summer-sc... |
| Description | Interview Life Extension Advocacy Foundation (LEAF) |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | During the Fourth Eurosymposium on Healthy Ageing (EHA), which was held in Brussels, Belgium in November 2018, I was interviewed by Life Extension Advocacy Foundation (LEAF), a non-profit organisation dedicated to promoting healthy human lifespan. |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://www.leafscience.org/an-interview-with-daniel-munoz-espin/ |
| Description | Invited Speaker CRUK Cambridge Institute - Lightning Talk Aerodigestive Programme. |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Professional Practitioners |
| Results and Impact | Invited speaker by the CRUK Cambridge Centre Aerodigestive Programme led by Dr Robert Rintoul. |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://crukcambridgecentre.org.uk/research/programmes/aerodigestive-cancer |
| Description | Invited Speaker-RESETAgeing |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Invited speaker by the RESETAgeing Scientific Committee. |
| Year(s) Of Engagement Activity | 2021 |
| URL | http://erachair.uc-biotech.pt/2021/05/12/1st-resetageing-conference/ |
| Description | Li/Fruk/Munoz-Espin Workshop |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | This was a Workshop organised to forge an interdisciplinary network between University of Cambridge and Southern University of Science and Technology (SUSTech) at Singapore. |
| Year(s) Of Engagement Activity | 2021 |
| Description | Nanoevening Event, Lecture Theatre, Institute for Manufacturing (IfM), West Cambridge, UK |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Postgraduate students |
| Results and Impact | This is a "Nanoevening" event organised by the Cambridge University Nanotechnology Society at the Institute for Manufacturing, University of Cambridge, on the 14th of March 2019. This event brings together students and researchers for a cross-disciplinary insight into the Nanotechnology research happening at Cambridge. My talk is aimed at introducing students to novel applications of Nanomedicine, in particular in how to use drug delivery tools to target senescent cells in preclinical models of cancer and disease. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://docs.google.com/forms/d/e/1FAIpQLSe59s-eamJKsSliWlIbHaQUL4ptERSjqKlLzL-hMOqYdaKPpA/viewform |
| Description | Organisation of a International Summer School: Discovery and Development of Diagnostics for the Early Detection of Cancer |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | As part of the CRUK Cambridge Centre Early Detection Programme we have organised the first international summer school on discovery and development of diagnostics for the early detection of cancer. As part of the Early Detection Programme Steering Committee I have participated actively in the design and organisation of the summer school. The summer school is aimed at those who are developing new technologies and interventions for the early detection of cancer and those who are interested in exploring this rapidly expanding and exciting field and is open to academic, corporate and student delegates. This ground-breaking summer school will focus on the scientific, clinical and policy challenges of developing and validating new screening technologies and interventions for the early detection of cancer. Participants will hear from experts across multiple disciplines on the science and technology of diagnostics through to clinical trials design, evidence review, regulatory perspectives and pathway to adoption, to the societal impacts of early cancer detection. Companies active in the development early cancer diagnostics, including Exact Sciences and Immunovia, will present case studies on their technologies and give insight into the route to market. In addition, participants will have the opportunity to participate in an opening debate and attend a Gala dinner with the after dinner talk to be given by Billy Boyle of Owlstone Medical Ltd. The summer school will be held in July 2019 in the tranquil surroundings of Robinson College in a state-of-the-art conference facility which is just minutes' walk from the historic city of Cambridge. The Summer School is aimed at training the next generation of research leaders in discovery and development of novel tools for Early Cancer Detection and Therapy, including product ideation, SWOT analysis, product definition, regulatory/reimbursement, translational steps, clinical trials, marketing, and commercialisation. We will introduce undergraduates, PhD students and postdocs in the industry and partnerships. Over the duration of the school, all delegates will participate in a team activity 'Envisioning New Diagnostics' led by the International School of Biomedical Diagnostics, Arizona State University (ASU), culminating in a presentation on the final day. ASU has considerable experience in this field, already offering a one-year, online Master of Science degree in Biomedical Diagnostics developed together with academic partner Dublin City University (DCU), and industry partners. The degree focuses on the global business and application of diagnostics in the healthcare and research arenas today. Myself and other group leaders have been recently trained in a two days course by Dr Carl Yamashiro (ASU) to lead the team activity as "Scrum Masters". Of note, David Macias-Gutierrez, senior postdoc in my lab and associated with this award, has also been trained as "Scrum Master". |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.earlydetectioncambridge.org.uk/news-events/international-summer-school |
| Description | Participation in the Cambridge Science Festival - Cambridge Academy for Science and Technology |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | My laboratory has been invited to contribute an activity in the Cambridge Science Festival 2019, as part of the CRUK Cambridge Centre Early Detection Programme. We have prepared different activities in a stand with a background of Cancer Early Detection. This includes a human torso model, a lung model, a real lung, an early detection activity to detect tumours with a UV fluorescent light in a lung model, a pinball game containing targetable tumours, and and adaptation of the "Invaders" computer game of the 80´s to a game with tumour cells (instead of invaders) and a therapeutic syringe shooting nanoparticles (instead of a spacecraft). |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.sciencefestival.cam.ac.uk/browse-2019-programme |
| Description | Preparation of a Video presenting the mission of the CRUK Cambridge Cancer Centre Early Detection Programme |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | As part of the CRUK Cambridge Cancer Centre Early Detection Programme I am involved in the generation of a video summarising the goals and mission of the Programme. I have been involved in the writing of the script and the design of the animations. This video will be included in the website of the Early Detection Programme and in Events for the general public. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.earlydetectioncambridge.org.uk |
| Description | RadNET Cambridge Seminar Series |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | Promoting collaborations, networking and critical mass of researchers interested in radiobiology and radiation oncology. |
| Year(s) Of Engagement Activity | 2021 |
| Description | Video presenting the mission and scope of the CRUK Cambridge Centre Early Detection Programme |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | As group leader of the CRUK Cambridge Centre Early Detection Programme I generated a video summarising the goals and mission of the Programme. I have been involved in the writing of the script and the design of the animations. This video is included in the website of the Early Detection Programme and used in relevant Events for the general public. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.earlydetectioncambridge.org.uk |