Cecilia Lindgren

Senescence Network was an incredible experience, especially the insightful presentation by Dr Daniel Muñoz-Espín from the Cancer Research UK Cambridge Centre. His session on "Senescent Ecosystems in Lung Cancer: Therapeutic Opportunities" was a deep dive into the innovative approaches towards cancer therapy using senescence.  Dr Muñoz-Espín's research focuses on the pivotal role of senescent cells within the tumour microenvironment and their impact on lung cancer progression. He highlighted groundbreaking methods to target these cells, aiming to disrupt their support of tumour growth. His work with the p16-3MR mouse model demonstrates significant findings where senolytic drugs selectively clear senescent cells, decreasing tumour growth and potentially increasing patient survival rates.  Another fascinating aspect of his talk was the use of advanced genomic and proteomic profiling to identify senescence-associated secretory phenotype (SASP) factors that promote tumorigenic processes. This approach could pave the way for therapies that treat and prevent cancer. I would like to express My heartfelt gratitude to the organizers for a well-curated event that provided us with such enriching insights. I am also deeply appreciative of Dr. Muñoz-Espín for his compelling presentation that significantly expanded our understanding of the potential of senolytic therapies in oncology.  Looking forward to more breakthroughs and the next meeting, which will continue this fascinating discussion on cancer and cellular senescence! #CancerResearch #Senescence #Oncology #MedicalInnovation #ICSA

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https://lnkd.in/eGv6bTTt Despite recent advances, some cancers still have a poor-prognosis - are we doing enough to understand and treat them? Read my Cancer World feature to read about some novel approaches and an assessment of what we need to be doing to meet these challenges.

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Our latest study published: We mapped Protein #Citrullination #Deimination in 6 #brain regions in #ParkinsonsDisease providing new insights into #mechanisms in #premotor stages. Our findings indicate that PAD (Peptidylarginine deiminase)-mediated protein citrullination plays roles in #metabolic, #immune, #cellsignalling and #neurodegenerative disease-related pathways across brain regions in early #premotor stages of PD, highlighting PADs as targets for future #therapeutic avenues. We also discuss possible involvement of #citrullination in the #gutbrainaxis in PD. UCL University of Westminster https://lnkd.in/e5-UWf9Y

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#CRISPR cures on-demand can and will be scaled nationwide. In this talk at the Oxford-Harrington symposium I argue - with data - that the first nation to do so will be the United Kingdom and describe an actionable path to that goal. https://lnkd.in/g4kxp4t3

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New work on Melanoma genetics. A real pleasure to work with Michael, Nicholas and William to do this. To develop targeted melanoma treatments, identifying genetic drivers, including non-coding regions, is crucial. Recent studies have focused on gene-adjacent elements, leaving intergenic distal regulatory elements largely unexplored. We used Hi-C chromatin contact data from melanoma cells to map distal, non-coding, promoter-interacting regulatory elements genome-wide. This “promoter-interaction network” was combined with whole-genome sequence and gene expression data. Using multivariate linear regression models, we identified distal somatic mutation hotspots that affect promoter activity, revealing novel, melanoma-specific mutations in promoter-interacting distal regulatory elements. Eight recurrently mutated hotspots were found, altering transcription factor binding motifs and affecting gene expression (e.g., HSPB7, CLDN1, ADCY9, FDXR), genes previously linked to cancer. Our study highlights new non-coding drivers in melanoma beyond the TERT promoter, offering insights into how non-coding mutations disrupt regulatory networks and contribute to melanoma. This framework integrates multiple biological data levels to uncover cancer-specific drivers.

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📣 The UCL Advanced Therapy Symposium hosted by the UCL Translational Research Office (TRO) and UCL Therapeutic Innovation Network (TINs) got off to a fantastic start showcasing some incredibly insightful talks from Professor Emma Morris discussing Gene editing for inborn errors of immunity followed by Professor Paul Gissen outlining a GTX/OTC case study and lastly a presentation from Professor Bobby Gaspar outlining the benefits of Haematopoietic stem cell gene therapy. Each gave a unique perspective on some of the advancements being made, and challenges overcome, in these respective areas. A vibrant panel discussion then ensued moderated by: Dr Anne Lane CEO, UCL Business Ltd, including Dr Richard Fagan, Director of BioPharm, UCL Business and external guest – Elisa Petris Lead Partner, Syncona Limited along with the esteemed speakers. 👇Key take home messages 👉 academic research is a primary source of innovation but further funding is needed to support academic proof of concept trials 👉 access to commercial GMP facilities can be a challenge for ATMP products 👉 regulations can often be over burdensome in advancing ATMP therapies 👉 development of medicines in rare diseases, in some instances, should be provided at cost as we have an ethical and moral responsibility to these patient populations 👉 the role of the UCL Translational Research Office (TRO) and UCL Business Ltd is a welcomed resource but UCL may need to consider further investment to facilitate translation of academic ATMP research 👉it’s vital for researchers to have access to suitable and sufficient resource, and funding, utilising collaborations and partnerships to progress advancements of ATMP innovations. #atmp #ucltro #clinicaltrials #clinicalresearch

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Really important new paper in Nature (Nature Portfolio) from Eric Vallabh Minikel and Matthew Nelson updating their own estimates for the benefit of using genomic evidence in drug discovery. The authors previously estimated that human genetic evidence roughly doubled the success rate of a drug going from clinical development to approval. In the new study, they revise that estimate to almost 3 times greater! The benefit was variable but significant among diverse therapy areas. In one analysis of 1147 targets reaching phase I with genetic support for any indication, the odds of advancing to a later stage in the pipeline were 82% higher for the indication with genetic support. The value of genome wide association study evidence for targets was not affected by effect size, recency of discovery, or allele frequency. Overall, the results indicated that we are *nowhere close* to exhausting the potential of new genetic evidence to advance new therapies to the clinic. In the Genome Odyssey, I discussed my view that in the future no drug company would advance a novel target to late stage development without some form of human genetic evidence supporting the target. I speculated that genomics would also regularly be used to inform drug safety (see references below). With new AI architectures supercharging many elements of drug discovery, the outlook for new therapies has never been brighter. New paper: https://lnkd.in/gKF2ihZc Genomics and Drug safety: https://lnkd.in/g9S75Jek Earlier paper from the same authors: https://lnkd.in/gmdyZXQt Paper from Robert Plenge & David Altshuler: https://lnkd.in/gX6N7cuE The Genome Odyssey: genomebook.info (As an aside, -> Nature Portfolio your abbreviations are out of control!)

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This article from The Guardian offers an insight into a study conducted by researchers at Stanford University (USA) and Nanyang Technological University (Singapore) published in the journal Nature Aging (Shen, X., Wang, C., Zhou, X. et al. Nonlinear dynamics of multi-omics profiles during human aging. Nat Aging (2024)). The study followed 108 volunteers aged between 25 years and 75 years over nearly seven years, examining various molecules (such as RNA, proteins, and metabolites) and microbes (including intestinal and skin bacteria, viruses, and fungi) at regular intervals. The results suggest that aging does not occur continuously in a linear pattern but accelerates during two key periods in life: the mid-40s and early 60s. The first wave of changes involved molecules associated with cardiovascular disease and the metabolism of caffeine, alcohol, and lipids. The second wave involved molecules related to immune system regulation, carbohydrate metabolism, and kidney function, with accelerated senile changes in skin and muscles occurring at both periods. These two periods could be ideal times for planning and implementing personal preventive or interventional programs such as exercise and dietary modifications.

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"To do no harm - and the most good – with AI in health care." This was the theme of the Responsible AI for Social and Ethical Healthcare (RAISE) Conference organised by Harvard Medical School last 30-31 October 2023. 🏥 I was fortunate to be invited to join this expert group to discuss key issues and immediate actions for healthcare leaders. Amongst other things, we discussed the following questions: ➡ How can AI in healthcare address systemic issues such as medical errors and access disparities? ➡ How should financial models for AI integration in healthcare promote accessibility and efficiency? ➡ How do we balance opt-out and opt-in models in patient consent to ensure inclusivity? ➡ How should liability be allocated between healthcare providers and AI manufacturers in practice? ➡ What mechanisms should be put in place to continuously evaluate the effectiveness and safety of AI tools? 📜 Our discussions culminated in a framework document outlining recommendations and exploring trade-offs to promote ethical, equitable, and responsible AI in healthcare globally. 🌍 Published in Nature Medicine: https://lnkd.in/dCSkKdB4 And New England Journal of Medicine AI: https://lnkd.in/dtkZVAFQ Laura Adams, Noah Brown, Atul Butte, Isaac Kohane Dave deBronkart, Jennifer Dixon, Jeffrey Drazen, Sara Hoffman, Jonathan Perlin, Rupa Sarkar, Effy Vayena

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At a time where data is enriching the Doctor-Patient relationship, here a good weekend read from Sarah Neville on Rita Charon and the impact of « narrative medicine » in modern care. «The practised narratologist, she says, can pick up a lot in a short period, even at a time when there is pressure on doctors to keep appointments as brief as possible. “As you develop your skills of attention, you will notice things about your patients. You will be listening at a much higher pitch. » A good weekend reflection on patient centricity and on one on one human interaction. Storytelling with the pioneer of ‘narrative medicine’ https://on.ft.com/4d0RJ7u #WeekendReads #PatientCentricity #Listening

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Delighted to contribute to this new work published last week in Nature Genetics on disease prediction. If our aim is to empower prevention of disease by producing the most powerful and accurate prediction tools then it makes sense to explore any and all data that might be available cost-effectively. In this work, machine learning is used to enhance UK Biobank genomic and medical data with biomarkers, some collected more than a decade before the onset of disease. These 67 blood and urine markers were supplemented in secondary analyses with thousands of proteomic markers. Prediction was impressive! For example, AUC was > 0.9 for 121 ICD10 codes. In most cases, the tool outperformed stand alone polygenic risk scores whereas in cases like breast cancer and prostate cancer where PRS are particularly powerful, the standalone PRS did better. Of course, the PRS literature also clearly shows that any and all data should be integrated for best prediction. The question as always is: what is the incremental cost-value of acquiring the new data? Finally, another benefit of identifying a disease early is you can expand your definition of the disease to enhance discovery of mechanism via genome-wide or phenome-wide association. https://lnkd.in/gQN4j63u Thanks and congrats to the amazing team led by Slavé Petrovski & Dimitrios Vitsios.

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📢 Research Alert: Global Burden of Antimicrobial Resistance 🌍 🎉 Kudos to Prof. Mohsen Naghavi, the GBD 2021 Antimicrobial Resistance Collaborators for their new study "Global burden of bacterial antimicrobial resistance 1990–2021: a systematic analysis with forecasts to 2050," now published in The Lancet. 📚 This comprehensive analysis covers the past three decades of bacterial antimicrobial resistance (AMR), estimating its burden across 204 countries and territories, and offering forecasts to 2050. 🔑 Key Insights: • Global Burden: In 2021, 4.71 million deaths were associated with bacterial AMR, with 1.14 million deaths directly attributable to bacterial AMR. • Age-related Trends: AMR mortality has decreased by over 50% among children under 5 years since 1990, while mortality for adults 70+ years increased by over 80%. • Resistance Growth: Resistance to carbapenems and methicillin-resistant Staphylococcus aureus (MRSA) rose significantly between 1990 and 2021. • Future Projections: By 2050, AMR could result in up to 8.22 million deaths annually if interventions are not strengthened. • Preventable Deaths 1: Improvements in health-care quality and access to antimicrobials could avert 92 million deaths between 2025 and 2050. • Preventable Deaths 2: Effective development and distribution of new Gram-negative drugs could avert 11 million deaths between 2025 to 2050 🌍 Impact: This study underscores the urgent need for global efforts in infection prevention, enhanced healthcare access, appropriate antibiotic use, and drug development to reduce the growing AMR burden. 👏 Funding: Supported by the UK Department of Health and Social Care's Fleming Fund using UKaid and the Wellcome Trust. 🔗 Dive deeper into the study here: https://lnkd.in/gf8B65AC #️⃣ #GlobalHealth #AMR #AntimicrobialResistance #PublicHealth #Lancet 🗓️ Published online 16 September 2024, this analysis provides insights to combat one of the 21st century’s biggest health threats.

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AI is really leading solutions with these daunting scientific problems... ------------------------------------- There are more than 7,000 rare and undiagnosed diseases globally. Although each condition occurs in a small number of individuals, collectively these diseases exert a staggering human and economic toll because they affect some 300 million people worldwide. Yet, with a mere 5 to 7 percent of these conditions having an FDA-approved drug, they remain largely untreated or undertreated. Developing new medicines represents a daunting challenge, but a new artificial intelligence tool can propel the discovery of new therapies from existing medicines, offering hope for patients with rare and neglected conditions and for the clinicians who treat them. The AI model, called TxGNN, is the first one developed specifically to identify drug candidates for rare diseases and conditions with no treatments.

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Very excited about this unique opportunity aiming to unravel a potential link between circadian regulation and cognition in AD https://lnkd.in/ep7g5ZCt

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•Did you know ? Over 7.6 million people in the UK have heart disease, and millions more live with undiagnosed diabetes. Diabetes and diabetic complications alone are costing the NHS  at least  £10 billion a year which is about 10% of its entire budget. These numbers are expected to rise, leading to a surge in neurodegenerative diseases and  dementia. •It is estimated that more than five million people in the UK are living with diabetes, which is an all-time high.  • Additionally, 850,000 people could be living with diabetes who are yet to be diagnosed.  •figures are rising year on year. (Source Diabetesuk.org.uk) •A massive surge in neurodegenerative diseases throughout the UK ( & globally) Neurodegeneration is now the third fastest growing disease globally "According to a report released by the United Nations, 1 in 11 world population was over 65 in 2019 and by 2050 the ratio will be almost doubled to 1 in 6. As the global population ages, the prevalence of neurodegenerative disorders, including Alzheimer’s disease (AD) and Parkinson’s disease (PD), is fast increasing. Notably, the number of cases of dementia in the developed world is projected to rise from 13.5 million in 2000 to 21.2 million in 2025, and to 36.7 million in 2050. The number of deaths caused by AD is now on par with the number of deaths caused by stroke, which is the third most common leading cause of death in the world".  https://lnkd.in/eYg4bm6c •Over 9,000 cases of Parkinson’s Disease currently in the UK   •By 2025, it’s estimated that over one million people in the UK will have a diagnosis of dementia – and almost all of us will know someone living with the condition

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Very pleased to see my research published in npj Genomic Medicine this week. This research was conducted as part of my PhD studies and focuses on the contributions of additional genetic variation to cognitive outcomes in carriers of neurodevelopmental associated copy number variants. To summarise, copy number variants (CNVs) are large deletions or duplications of segments of our genomes. Most of us carry CNVs however some rare CNVs have been associated with neuropsychiatric conditions such as intellectual disability, schizophrenia, and autism. We refer to these as ND-CNVs and they include 22q11.2 deletion and the Prader-Willi syndrome duplication. Despite strong associations with neuropsychiatric conditions, many ND-CNV carriers have variable outcomes ranging from no clinical outcome to multi-morbid psychiatric, neurological and physical health outcomes. Even individuals within the same family with the same ND-CNV can have dramatically different outcomes. This can make genetic counselling difficult and confusing for parents/caregivers. Findings from clinically-ascertained cohorts suggest that additional genetic variation outside of the ND-CNV location in the genome can modify these outcomes, though these cohorts show some bias toward individuals with larger effect ND-CNVs and greater psychiatric needs. Here, I wanted to understand whether this is true for ND-CNV carriers in a population-based cohort with generally smaller effect ND-CNVs and to see whether this additional genetic variation could be used to stratify ND-CNV carrier pre-disposed to psychiatric outcomes. Using data from the UK Biobank, the world's largest biomedical cohort, I investigated whether common genetic variants associated with higher cognitive ability and rare genetic variants associated with lower cognitive ability modify ND-CNV carrier verbal-numeric scores. I found that enrichment for common genetic variants, as measured by polygenic scores, was associated with higher verbal numeric scores in ND-CNV carriers. This was not the case for rare genetic variants. Moreover, those ND-CNV carriers in the lowest decile of cognition and polygenic scores, had a 2-5 fold increase in low verbal-numeric scores relative to the baseline rate. These findings highlight that polygenic scores may serve a role in improving precision genetic diagnostics in the clinic and may help to stratify patients for interventions. I want to say a massive thank you to my supervisors, Prof. Louise Gallagher and Dr. Lorna M. Lopez for all their support with this research, and my co-investigators, Dr. Fiana Ní Ghrálaigh, Dr. Cathal Ormond, Dr. Elizabeth Heron, and Prof. George Kirov, for all their help and expertise. This work was supported by AIMS-2-TRIALS and was conducted using the UK Biobank Resource under application no. 48915. Want to know more, check out the paper here: https://lnkd.in/gtgsamZi

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Good to be part of the Lung Innovation and Research Group and to see this important report published. While our Chronic Respiratory Infection Translational Challenge, is focusing on progressing discoveries that can intervene earlier, reduce treatment burden, and enhance the quality of life people living with cystic fibrosis and bronchiectasis, there are common challenges across respiratory conditions. These priorities highlight those challenges and offer solutions to fix the lung research pipeline – now is the time for action. #chronicrespiratoryinfection #lunghealth #lifesciences  #cysticfibrosis #bronchiectasis

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The UK Biobank's availability of protein measurements and whole exome sequence data has enabled new discoveries in cancer research. A recent study investigated 1463 plasma proteins and their associations with 19 cancers and 9 cancer subsites in UK Biobank participants over an average 12-year follow-up. The results identified 618 protein-cancer associations, including some detectable more than seven years before cancer diagnosis. Genetic analyses provided supportive evidence for 29 of these associations, with four showing strong support from long time-to-diagnosis and both cis-pQTL and exGS analyses. The study's findings suggest a possible role of blood proteins in cancer development and may inform future cancer prevention strategies. Read more about this study in the link below. #cancerresearch #UKBiobank #proteomics #genetics

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