This document discusses bridging research and healthcare by translating biomarkers into patient treatment. It provides background on Prof. Alain van Gool and his roles at TNO, Radboud University Nijmegen Medical Centre, and Radboud University Nijmegen. It outlines the need for biomarkers in pharmaceutical drug development and personalized healthcare to address the biomarker innovation gap and develop personal profiles for conditions like oncology and diabetes. Progress may be made through open innovation networks.
2018 03-01 International Conference on Perspectives in Precision Medicine, Co...Alain van Gool
This keynote lecture reviews the historical and ongoing investments in public-private partnerships related to precision medicine and the related technological infrastructures. It served as example to the Danish community how translational biomarkers in precision medicine can be organised, as basis for further collaboration between Denmark and Netherlands.
2014 07-08 Selectbio Biomarkers 2014, CambridgeAlain van Gool
The document discusses biomarkers in personalized healthcare from discovery to clinical diagnostics, providing an overview of the speaker's experience in academia, pharmaceutical industry, and applied research focusing on biomarkers and omics technologies. It also describes the Radboud University Medical Center's focus on personalized healthcare through its technology centers and biomarker research on conditions like metabolic syndrome. The discussion emphasizes how biomarkers are evolving from diagnosis to tools that enable personalized and participatory healthcare approaches.
2021 06-14 EATRIS-Plus summer school, Alain van GoolAlain van Gool
Introductory lecture for the 100 participant summer school of the EATRIS-Plus project, outlining personalized medicine, biomarker and multi-omics strategies and use cases.
2018 11-26 KNAW-AcTI symposium Personalized Health, Amsterdam, Alain van GoolAlain van Gool
Lecture at a citizen discussion evening, reviewing the promises and (ethical) considerations of technology developments to support personalized health, organised by the Royal Academy of Sciences and the Netherlands Academy of Technology and Innovation.
2021 03-25 11th World Clinical Biomarkers & Companion Diagnostics, Alain van ...Alain van Gool
Closing keynote of a 3-day conference on clinical biomarkers and companion diagnostics, organised by Hanson Wade, outlining the power of omics approaches in healthcare and translation of inovations to impact.
2020 08-28 SensUs Event 2020 keynote, Eindhoven, Alain van GoolAlain van Gool
Closing keynote for international students participating in the SensUs Event 2020, where they designed and created a novel sensor for drug level monitoring in epilepsy treatment. Lecture outlined innovations in biomarkers in personalized health(care).
2019 10-14 2nd Int Congress on Precision Medicine, Munich, Alain van GoolAlain van Gool
Opening lecture at the 2nd International Congress on Precision Medicine in Munich, outlining progress in omics-based biomarkers for rare diseases, biomarker innovation gaps and multi-partner initiatives to bridge those gaps to applications. Also reviewed the highlights of our recently published Handbook of Biomarkers and Precision Medicine.
2018 03-01 International Conference on Perspectives in Precision Medicine, Co...Alain van Gool
This keynote lecture reviews the historical and ongoing investments in public-private partnerships related to precision medicine and the related technological infrastructures. It served as example to the Danish community how translational biomarkers in precision medicine can be organised, as basis for further collaboration between Denmark and Netherlands.
2014 07-08 Selectbio Biomarkers 2014, CambridgeAlain van Gool
The document discusses biomarkers in personalized healthcare from discovery to clinical diagnostics, providing an overview of the speaker's experience in academia, pharmaceutical industry, and applied research focusing on biomarkers and omics technologies. It also describes the Radboud University Medical Center's focus on personalized healthcare through its technology centers and biomarker research on conditions like metabolic syndrome. The discussion emphasizes how biomarkers are evolving from diagnosis to tools that enable personalized and participatory healthcare approaches.
2021 06-14 EATRIS-Plus summer school, Alain van GoolAlain van Gool
Introductory lecture for the 100 participant summer school of the EATRIS-Plus project, outlining personalized medicine, biomarker and multi-omics strategies and use cases.
2018 11-26 KNAW-AcTI symposium Personalized Health, Amsterdam, Alain van GoolAlain van Gool
Lecture at a citizen discussion evening, reviewing the promises and (ethical) considerations of technology developments to support personalized health, organised by the Royal Academy of Sciences and the Netherlands Academy of Technology and Innovation.
2021 03-25 11th World Clinical Biomarkers & Companion Diagnostics, Alain van ...Alain van Gool
Closing keynote of a 3-day conference on clinical biomarkers and companion diagnostics, organised by Hanson Wade, outlining the power of omics approaches in healthcare and translation of inovations to impact.
2020 08-28 SensUs Event 2020 keynote, Eindhoven, Alain van GoolAlain van Gool
Closing keynote for international students participating in the SensUs Event 2020, where they designed and created a novel sensor for drug level monitoring in epilepsy treatment. Lecture outlined innovations in biomarkers in personalized health(care).
2019 10-14 2nd Int Congress on Precision Medicine, Munich, Alain van GoolAlain van Gool
Opening lecture at the 2nd International Congress on Precision Medicine in Munich, outlining progress in omics-based biomarkers for rare diseases, biomarker innovation gaps and multi-partner initiatives to bridge those gaps to applications. Also reviewed the highlights of our recently published Handbook of Biomarkers and Precision Medicine.
2014 08-20 Radboudumc-Health Valley-LSH: Personalized Healthcare through inte...Alain van Gool
1) Personalized healthcare aims to stratify patients based on multi-level diagnoses and patient preferences to select personalized therapies.
2) Radboud University Medical Center is working to advance personalized healthcare through various technology centers that integrate omics data like genomics, glycomics, and metabolomics.
3) Key goals include developing diagnostic tests and personalized therapies through collaborative projects, working with innovators and spin-off companies, and integrating data and technologies.
2020 09-07 European Center Pharmaceutical Medicine course Biomarkers, Basel, ...Alain van Gool
Tutorial lecture on biomarkers for pharmaceutical industry R&D professionals, outlining status, potential and challenges of biomarkers in pharma, clinic and society.
2020 02-10 European Center Pharmaceutical Medicine course - biomarkers, Basel...Alain van Gool
This document discusses biomarkers and personalized healthcare. It begins with an overview of biomarkers in the pharmaceutical industry and how they are used from drug discovery through clinical trials. It then discusses biomarkers in academic research and healthcare, and how emerging digital biomarkers could enable personalized health monitoring. The presentation identifies some translational innovation gaps, and concludes with an outlook on how biomarkers and multi-omics approaches will continue to advance personalized diagnosis and therapies.
Inger Björck: The Antidiabetic Food CentreFoodbest DK/SE
Inger Björck shares her experiences with working directly in a scientific research centre with the formal responsibility to create spin-offs and patents.
2019 09-23 COST CliniMARK summerschool, Spetses, Alain van GoolAlain van Gool
Opening lecture of the COST CliniMARK summer school 'Approaches for Biomarker Discovery and Validation'. Extensive introduction in biomarker approached used in pharmaceutical industry, academic research and clinical care, and society, combined with review of biomarker innovation gaps and outlook.
2018 11-02 Healthy Brain Cohort progress meeting, Nijmegen, Alain van GoolAlain van Gool
Highlights and anecdotes from my experiences in interdisciplinary research in big data for personalized healthcare whilst working in Europe, USA and Singapore
2016-02-18 Innovation for Health 2016 conference, Rotterdam Alain van GoolAlain van Gool
Lecture on personalized healthcare in a great session at the Innovation for Health 2016 conference, discussing opportunities and challenges with 800 scientists, enterpreneurs and care professionals.
This document provides a summary of the background and qualifications of Martin C. Michel, MD, MAE, FBPhS. He has over 30 years of experience in clinical research, experimental research, and their integration in both academia and industry. Key areas of expertise include urogenital and cardiovascular medicine. He has held senior leadership roles at universities and large pharmaceutical companies. He has authored over 500 publications that have been cited over 20,000 times and has an h-index of 73. He is recognized as a leader in his field and has received numerous honors and awards for his contributions to pharmacology research.
Lecture on biomarkers (principles, potentials, pitfalls) for 200 pharmaceutical professionals as part of the IMI Pharma Train course organised by the European Center for Pharmaceutical Medicine
Great evening with the Rotary Oss where I got the opportunity to discuss current and future prospects in personalized healthcare with a good group of interested people.
Este documento presenta una guía para la atención a la diversidad dirigida a docentes. Explica que la atención a la diversidad nace de la necesidad de ofrecer una educación adaptada a las características y necesidades de todos los estudiantes. Define la atención a la diversidad y describe factores como la diversidad de intereses, capacidades, estilos cognitivos, necesidades, motivación y cultura. Recomienda que los docentes se capaciten en adaptación curricular, potencien actividades que permitan a los estudiantes expresarse y acojan la legisl
The document describes the activities of a gnome named Pronto during his visit to the Bank of Powell. Pronto got acquainted with Betty, rode in the bank's drive-up tube, and greeted customers. He then went rock climbing, worked on his hunting skills and caught pheasants for dinner. Later, Pronto relaxed in the sun, took a motorcycle ride, and entered a fish catching contest at the bank before saying farewell on his last day.
Ryan Eagle founded Eagle Web Assets Inc. in 2004 after several websites hit massive success, harnessing nearly a million unique visitors a day. From the instant success of these websites, the business model was reproduced and scaled into an empire of over 450 niche websites.http://www.eaglewebassets.com/ryan-eagle.php
Consumer barriers to mobile internet adoption in AsiaTuan Anh Nguyen
This research examines why more than 2 billion people in the region can access the internet but are holding back from doing so.
This includes data from six markets in the region: China, India, Indonesia, Philippines, Thailand and Vietnam with approximately 1,000 people in each country
This document discusses emerging digital marketing trends for 2016. It finds that the top trend is the rise of video across digital platforms, as consumers are increasingly consuming video content on websites, social media, and in online ads. It also discusses other trends like influencer marketing, increased "buy now" functionality on social media, using social listening to inform brand decisions, and mapping cross-device consumer journeys. The overarching theme is that all of these trends are focused on putting consumers at the center of marketing strategies. Brands will need to respond by soliciting consumer input and feedback to better understand and meet consumer needs.
The document provides guidance on creating challenges to solve problems through open innovation. It discusses why challenges are useful, what challenge design entails, and the basics of setting up a challenge, including: researching the problem space, providing background information, establishing judging criteria, securing funding, and running the challenge. The overall process involves diversifying input, letting others help find solutions, and amplifying creativity through open participation in challenges.
2014 08-20 Radboudumc-Health Valley-LSH: Personalized Healthcare through inte...Alain van Gool
1) Personalized healthcare aims to stratify patients based on multi-level diagnoses and patient preferences to select personalized therapies.
2) Radboud University Medical Center is working to advance personalized healthcare through various technology centers that integrate omics data like genomics, glycomics, and metabolomics.
3) Key goals include developing diagnostic tests and personalized therapies through collaborative projects, working with innovators and spin-off companies, and integrating data and technologies.
2020 09-07 European Center Pharmaceutical Medicine course Biomarkers, Basel, ...Alain van Gool
Tutorial lecture on biomarkers for pharmaceutical industry R&D professionals, outlining status, potential and challenges of biomarkers in pharma, clinic and society.
2020 02-10 European Center Pharmaceutical Medicine course - biomarkers, Basel...Alain van Gool
This document discusses biomarkers and personalized healthcare. It begins with an overview of biomarkers in the pharmaceutical industry and how they are used from drug discovery through clinical trials. It then discusses biomarkers in academic research and healthcare, and how emerging digital biomarkers could enable personalized health monitoring. The presentation identifies some translational innovation gaps, and concludes with an outlook on how biomarkers and multi-omics approaches will continue to advance personalized diagnosis and therapies.
Inger Björck: The Antidiabetic Food CentreFoodbest DK/SE
Inger Björck shares her experiences with working directly in a scientific research centre with the formal responsibility to create spin-offs and patents.
2019 09-23 COST CliniMARK summerschool, Spetses, Alain van GoolAlain van Gool
Opening lecture of the COST CliniMARK summer school 'Approaches for Biomarker Discovery and Validation'. Extensive introduction in biomarker approached used in pharmaceutical industry, academic research and clinical care, and society, combined with review of biomarker innovation gaps and outlook.
2018 11-02 Healthy Brain Cohort progress meeting, Nijmegen, Alain van GoolAlain van Gool
Highlights and anecdotes from my experiences in interdisciplinary research in big data for personalized healthcare whilst working in Europe, USA and Singapore
2016-02-18 Innovation for Health 2016 conference, Rotterdam Alain van GoolAlain van Gool
Lecture on personalized healthcare in a great session at the Innovation for Health 2016 conference, discussing opportunities and challenges with 800 scientists, enterpreneurs and care professionals.
This document provides a summary of the background and qualifications of Martin C. Michel, MD, MAE, FBPhS. He has over 30 years of experience in clinical research, experimental research, and their integration in both academia and industry. Key areas of expertise include urogenital and cardiovascular medicine. He has held senior leadership roles at universities and large pharmaceutical companies. He has authored over 500 publications that have been cited over 20,000 times and has an h-index of 73. He is recognized as a leader in his field and has received numerous honors and awards for his contributions to pharmacology research.
Lecture on biomarkers (principles, potentials, pitfalls) for 200 pharmaceutical professionals as part of the IMI Pharma Train course organised by the European Center for Pharmaceutical Medicine
Great evening with the Rotary Oss where I got the opportunity to discuss current and future prospects in personalized healthcare with a good group of interested people.
Este documento presenta una guía para la atención a la diversidad dirigida a docentes. Explica que la atención a la diversidad nace de la necesidad de ofrecer una educación adaptada a las características y necesidades de todos los estudiantes. Define la atención a la diversidad y describe factores como la diversidad de intereses, capacidades, estilos cognitivos, necesidades, motivación y cultura. Recomienda que los docentes se capaciten en adaptación curricular, potencien actividades que permitan a los estudiantes expresarse y acojan la legisl
The document describes the activities of a gnome named Pronto during his visit to the Bank of Powell. Pronto got acquainted with Betty, rode in the bank's drive-up tube, and greeted customers. He then went rock climbing, worked on his hunting skills and caught pheasants for dinner. Later, Pronto relaxed in the sun, took a motorcycle ride, and entered a fish catching contest at the bank before saying farewell on his last day.
Ryan Eagle founded Eagle Web Assets Inc. in 2004 after several websites hit massive success, harnessing nearly a million unique visitors a day. From the instant success of these websites, the business model was reproduced and scaled into an empire of over 450 niche websites.http://www.eaglewebassets.com/ryan-eagle.php
Consumer barriers to mobile internet adoption in AsiaTuan Anh Nguyen
This research examines why more than 2 billion people in the region can access the internet but are holding back from doing so.
This includes data from six markets in the region: China, India, Indonesia, Philippines, Thailand and Vietnam with approximately 1,000 people in each country
This document discusses emerging digital marketing trends for 2016. It finds that the top trend is the rise of video across digital platforms, as consumers are increasingly consuming video content on websites, social media, and in online ads. It also discusses other trends like influencer marketing, increased "buy now" functionality on social media, using social listening to inform brand decisions, and mapping cross-device consumer journeys. The overarching theme is that all of these trends are focused on putting consumers at the center of marketing strategies. Brands will need to respond by soliciting consumer input and feedback to better understand and meet consumer needs.
The document provides guidance on creating challenges to solve problems through open innovation. It discusses why challenges are useful, what challenge design entails, and the basics of setting up a challenge, including: researching the problem space, providing background information, establishing judging criteria, securing funding, and running the challenge. The overall process involves diversifying input, letting others help find solutions, and amplifying creativity through open participation in challenges.
2015 09-10 Health Valley meets Topsector LSH Alain van GoolAlain van Gool
Outline of the Radboud way towards Personalized Health(care)in a great session between health Valley, Topsector LSH, Radboudumc, province Gelderland and others.
A empresa de tecnologia anunciou um novo sistema operacional para computadores pessoais. O novo sistema operacional tem uma interface simplificada e recursos aprimorados de segurança e privacidade para proteger os usuários. A nova versão será lançada globalmente no próximo ano e espera-se que seja bem recebida pelos consumidores preocupados com a segurança online.
Este manual explica cómo implementar Google Analytics en una tienda Magento para entender y mejorar el rendimiento. Detalla la configuración de perfiles y filtros en Google Analytics, así como el seguimiento de eventos, métricas de e-commerce y optimización on-site para mejorar el posicionamiento orgánico.
Como vender en Facebook
Nos especializamos en el desarrollo de soluciones de e-commerce, con alto valor agregado para nuestros clientes, y una marcada orientación a resultados mensurables.
Para obtener una implementación eficaz es fundamental conocer y entender el modelo de negocio de nuestros clientes. De esta manera podremos maximizar el ROI del canal y la experiencia online de compra. El canal E-commerce debe ser tratado como un punto de venta mas dentro de la organización.
Proveemos soluciones de negocio pensadas para cada necesidad
• Indumentaria
• Electro hogar
• Alimentos
• Telefonía
• Real Estate
• Agro
• Cosmetica
• Espectáculos y entretenimiento
• Venta mayorista
• Retail en general
Show and Tell: Building Applications on Cisco Open SDN Controller Cisco DevNet
The Cisco Open SDN Controller is based on the OpenDaylight SDN Controller and meets the need of Service Providers for a flexible, powerful, and commercially-supported multi-protocol controller. In this 60 minute session we will give an overview of the Cisco Open SDN Controller, explaining how the controller is packaged and the features it supports, and showing examples of applications that are supported by the controller. We will also outline the new features and applications that will be introduced in the next release of the controller. Taught by Giles Heron.
50 aniversario colegio 28 junio 2016 presentación claustro parte mario profesjcmario
Este documento parece tratar sobre un posible reencuentro de viejas glorias de diferentes ámbitos como música, política, vida, televisión, ocio e internacional. También menciona a personajes y cómo era la ciudad en el pasado.
Pharma-Nutrition: a pharma perspective. View how the pharmaceutical drug development model can and should be combined with the nutrition field to optimally implement personalized healthcare.
2013-10-10 GTC Bio Biomarker Europe Summit 2013, BerlinAlain van Gool
Using system biomarkers to combat preventable diseases
Prof. Alain van Gool discussed using a systems biology approach and biomarkers to develop personalized health management strategies. This involves continuously monitoring individuals using routine biomarkers to detect changes and "omics" data to understand the changes. Biomarker panels can provide a functional fingerprint to make personalized decisions on health and disease management interventions like nutrition, lifestyle changes, or pharmaceutical drugs. Field labs are proposed to test these concepts in real-life settings. A systems approach is needed to better understand and define diseases, leading to more mechanism-based treatments.
2012 19-11 EC DG R&I biomarker lecture, BrusselsAlain van Gool
Invited lecture for the European Commission, Directorate General Research & Innovation, to outline developments and needs in biomarker research for biomedical applications.
2013-04-23 Top Institute Pharma Spring meeting, UtrechtAlain van Gool
Companion diagnostics use biomarkers as diagnostic tools to identify patients who will respond well to specific drug therapies. The presentation discusses the increasing use of companion diagnostics in oncology drug development and clinical trials. It provides examples of biomarkers used to identify patients with melanoma who will benefit from BRAF inhibitor drugs. While some biomarkers like BRAFV600E mutations are useful targets, tumor heterogeneity poses a challenge for companion diagnostics. The presentation calls for improving the pipeline for validating biomarkers and developing them into clinical diagnostic tests.
2014 02-24 Oxford Global biomarker congress, ManchesterAlain van Gool
This document summarizes a presentation given by Alain van Gool on biomarkers in a changing world. It discusses the shift from personalized medicine to personalized healthcare, which takes a more holistic systems view of an individual. It also notes disruptive technologies that can accelerate biomarker development and the need to translate biomarkers into useful tools. Throughout, it provides examples of challenges like tumor heterogeneity and factors beyond genetics that influence disease and response to treatment.
2015 10-06 Building Bridges Biomarker symposium FIMM Helsinki, Alain van GoolAlain van Gool
A unique honour and opportunity to give a 1.5 hour lecture to young biomarker scientists to introduce biomarkers and their importance in translational medicine and personalized healthcare.
2015 09-14 Precision Medicine 2015, London, Alain van GoolAlain van Gool
Outline of my view hoe personalized health(care) is more than just targeted medicines, also including personal motivation and actions towards disease prevention. It also outlines 4 key factors that should be in order for optimal personalized health(care): 1. start with patients first, 2. Accelerate translation research to application, 3. Copy best practice, 4. Spread the word.
2015 07-03 Nanonext NL Alain van Gool, AmsterdamAlain van Gool
The document discusses implementing personalized healthcare through measuring biomarkers. It notes that while many biomarkers have been discovered, few are validated and applied in diagnostic tests. There is also a gap in translating biomarkers into point-of-care applications. The document advocates for open innovation networks to help validate biomarkers across multiple centers and standardize clinical applications. Ultimately, the focus of personalized healthcare should be on the patient by providing individualized follow-up based on their molecular and clinical measurements.
2015 12-09 Opening Radboud Translational Medicine, Nijmegen, Alain van GoolAlain van Gool
Keynote opening lecture at the grand opening of our new cyclotron facility, embedded in Radboud Translational Medicine and part of our Radboudumc Technology Centers. See http://www.radboudtranslationalmedicine.nl/nl/ for details.
2013-10-02 Dutch CC symposium on Personalized Healthcare, EdeAlain van Gool
This document summarizes a presentation about companion diagnostics and personalized healthcare. It discusses how companion diagnostics can identify the right drug, dose, and timing for a patient by using biomarkers to characterize biological systems and diseases. It provides examples of companion diagnostic use in oncology and challenges in biomarker development and validation. Overall it advocates applying well-characterized therapies guided by biomarkers to better understand and treat disease in a personalized manner.
2016 05-24 Kick-off The Danish Biomarker Network, Copenhagen, Alain van GoolAlain van Gool
Keynote lecture given at the kick-off of The Danish Biomarker Network in Copenhagen for a great audience of enthousiastic patients, biotech/pharma developers and ICT experts.
2018 12-07 Danone-Nutricia Precision Nutrition Forum, Utrecht, Alain van GoolAlain van Gool
1. The document discusses innovations in personalized health and healthcare using various omics technologies and big data. It highlights developments in genomics, metabolomics, glycomics, and proteomics that enable personalized diagnosis and therapy.
2. Several examples are provided of how multi-omics approaches combined with whole exome sequencing can identify new disease mechanisms and biomarkers for precision medicine in genetic disorders.
3. The development of systems approaches that integrate multi-level omics data, environment, and lifestyle factors is needed to create personalized data-driven tools to monitor health and provide customized recommendations.
2015 06-02 Steering group 'Personalized Medicine: eligible or not'Alain van Gool
Update for the steering group of the project "Personalized Medcine: eligble or not?", aiming to define whether and how to implement pharmacogenetic screening by first line care practitioners.
2013-10-23 DTL Next Generation Life Sciences Event, UtrechtAlain van Gool
This document summarizes a case study on identifying microRNA targets for miRNA-based cancer therapeutics. Researchers from Radboud University Medical Center, TNO, and InteRNA collaborated using various omics technologies. They screened 1120 miRNAs to identify those that inhibit epithelial-to-mesenchymal transition and cancer cell invasion/metastasis. Proteomics and transcriptomics were used to validate miRNA targets, and CyTargetLink integrated the multi-omics data. The collaboration aimed to improve understanding of miRNA effects on cancer metastasis through integrated systems biology approaches.
2018 11-28 SAB Interreg BIC project Baltic Sea Region, Copenhagen, Alain van ...Alain van Gool
Overview of the current challenges in biomarker commercialisation, to kick off the scientific advisory board meeting with the multidisciplinary Interreg BIC project team.
2023-11-14 Biomarkers Europe 2023, Berlin, Alain van Gool.pdfAlain van Gool
Lecture at the Biomarkers Europe 2023 conference for an audience of pharma scientists and omics/data solution providers. I outlined several initiatives of potential interest and discussed development of our sensitive personalized clinical biomarker test for minimal residual disease monitoring in multiple myeloma.
2023-11-09 HealthRI Biobanking day_Amsterdam_Alain van Gool.pdfAlain van Gool
Examples of lessons learned in Omics-based biomarker studies from myself and colleagues in X-omics and EATRIS, for an audience of biobankers, researchers and diagnostic/clinical chemistry experts.
2023-04-20 EATRIS-Plus Summerschool, Lisbon, Alain van GoolAlain van Gool
Closing keynote lecture at the EATRIS-Plus summerschool on personalised medicine, outlining developments, opportunities, challenges and recommendations to do next in this exciting era of personalised medicine.
2022-11-23 DTL Future of data-driven life sciences, Utrecht, Alain van Gool.pdfAlain van Gool
A pitch on directions to improve experimental reproducibility, illustrated by examples of past experiences. I made the plee to move from 'Proudly invented here' to 'Proudly copyied from', to re-use each other's eperiences in successes and failures.
2022-10-12 The future of population health_Alain van Gool.pdfAlain van Gool
1) Exponential developments in omics technologies like genomics, proteomics, and metabolomics are driving more personalized approaches to healthcare.
2) Mass spectrometry methods have been developed to sensitively detect minimal residual disease in multiple myeloma patients from plasma samples, allowing for dynamic monitoring and earlier detection of relapse compared to traditional methods.
3) Large-scale multi-omics studies incorporating data from various sources can provide a more holistic view of health and disease at both the individual and population levels, supporting personalized prevention and treatment approaches.
2022-09-08 ECPM Digital Biomarkers and AI, Basel, Alain van Gool.pdfAlain van Gool
Lecture for 150 pharma professionals to outline the potentials and things-to-do with digital biomarkers, as part of a ECPM training on digitization and AI in drug development.
2022-04-14 EuroMedLab, Munich, Alain van GoolAlain van Gool
Keynote lecture at the EuroMedLab 2021 providing an audience of clinical chemists and laboratory medicine scientists with advancements of multi-omics applications in personalized healthcare, and challenges that we need to solve as translational scientists.
2021 12-10 Amalia Science Day, Nijmegen, Alain van GoolAlain van Gool
This document discusses the use of omics technologies like genomics, proteomics, and glycoproteomics in pediatric healthcare. Specifically, it describes a study that used glycoproteomics to analyze blood samples from children with febrile illness to distinguish between viral and bacterial infections. The analysis identified glycoprotein biomarkers that could accurately classify 70-80% of samples as viral or bacterial. Integrating multiple omics data through machine learning approaches may provide a more comprehensive understanding of diseases and lead to personalized diagnosis and treatment.
2019 06-19 Dutch association for clinical chemistry and laboratory medicine -...Alain van Gool
Sharing my views on how X-omics biomarker analyses through next gen sequencing and mass spectrometry will change the landscape of diagnostics and clinical chemistry in the near future.
Lecture describing workflows and case studies from the Translational Metabolic Laboratory @Radboudumc how to translate x-omics biomarker signatures to clinical implementation. I also highlighted new developments to join forces in the Netherlands X-omics Initiative, United for Metabolic Disease and events/book launches in the next months.
2019 03-14 Health Valley Event 2019, Nijmegen, Alain van GoolAlain van Gool
Lecture on innovations in personalized healthcare using an integrated X-omics approach towards personalized diagnostics, as part of the regional ambitious TopFit program.
2019 02-21 Oxford Global 14th Biomarker Congress, Manchester, Alain van GoolAlain van Gool
1. Professor Alain van Gool presented on using clinical x-omics to drive personalized healthcare.
2. He described case studies where combining different omic approaches like genomics, metabolomics, and glycomics led to novel disease mechanisms and therapies for rare genetic diseases.
3. Van Gool advocated for increased collaboration and standardization of omic technologies to advance precision medicine and bring clinical multi-omics to higher diagnostic and therapeutic levels.
2018 12-04 CHAINS X-omics workshop lecture, Veldhoven, Alain van GoolAlain van Gool
Introducing the innovations we plan to do in the Netherlands X-omics Initative, together with other X-omics consortium members, at a dedicated X-omics workshop at the annual congres of the Netherlands Chemistry society.
Does Over-Masturbation Contribute to Chronic Prostatitis.pptxwalterHu5
In some case, your chronic prostatitis may be related to over-masturbation. Generally, natural medicine Diuretic and Anti-inflammatory Pill can help mee get a cure.
Osteoporosis - Definition , Evaluation and Management .pdfJim Jacob Roy
Osteoporosis is an increasing cause of morbidity among the elderly.
In this document , a brief outline of osteoporosis is given , including the risk factors of osteoporosis fractures , the indications for testing bone mineral density and the management of osteoporosis
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
share - Lions, tigers, AI and health misinformation, oh my!.pptxTina Purnat
• Pitfalls and pivots needed to use AI effectively in public health
• Evidence-based strategies to address health misinformation effectively
• Building trust with communities online and offline
• Equipping health professionals to address questions, concerns and health misinformation
• Assessing risk and mitigating harm from adverse health narratives in communities, health workforce and health system
TEST BANK For Community and Public Health Nursing: Evidence for Practice, 3rd...Donc Test
TEST BANK For Community and Public Health Nursing: Evidence for Practice, 3rd Edition by DeMarco, Walsh, Verified Chapters 1 - 25, Complete Newest Version TEST BANK For Community and Public Health Nursing: Evidence for Practice, 3rd Edition by DeMarco, Walsh, Verified Chapters 1 - 25, Complete Newest Version TEST BANK For Community and Public Health Nursing: Evidence for Practice, 3rd Edition by DeMarco, Walsh, Verified Chapters 1 - 25, Complete Newest Version Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Pdf Chapters Download Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Pdf Download Stuvia Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Study Guide Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Ebook Download Stuvia Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Questions and Answers Quizlet Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Studocu Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Quizlet Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Stuvia Community and Public Health Nursing: Evidence for Practice 3rd Edition Pdf Chapters Download Community and Public Health Nursing: Evidence for Practice 3rd Edition Pdf Download Course Hero Community and Public Health Nursing: Evidence for Practice 3rd Edition Answers Quizlet Community and Public Health Nursing: Evidence for Practice 3rd Edition Ebook Download Course hero Community and Public Health Nursing: Evidence for Practice 3rd Edition Questions and Answers Community and Public Health Nursing: Evidence for Practice 3rd Edition Studocu Community and Public Health Nursing: Evidence for Practice 3rd Edition Quizlet Community and Public Health Nursing: Evidence for Practice 3rd Edition Stuvia Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Pdf Chapters Download Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Pdf Download Stuvia Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Study Guide Questions and Answers Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Ebook Download Stuvia Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Questions Quizlet Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Studocu Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Quizlet Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Stuvia
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
1. Bridging research & healthcare:
Translating biomarkers into patient treatment
Prof. Alain van Gool
Netherlands Organisation for Applied Scientific Research (TNO)
Radboud University Nijmegen Medical Centre
Radboud University Nijmegen
Laboratorium voor Klinische Chemie en Haematologie
UMC Utrecht
29st October 2013
3. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
3
Background
Molecular and cellular biology, biochemistry (BSc Eindhoven, MSc Leiden)
1991-1998 Academia - Transcription-coupled DNA repair (PhD, NL)
- DNA recombination (post-doc, UK)
1999-2011 Pharma - Organon (1999-2007) (NL)
- Schering-Plough (2007-2009) (NL, SG)
- Merck/MSD (2009-2011) (SG)
2011 – present:
Netherlands Organisation for Applied Scientific Research (TNO) (Nov 2011)
– Coordinator Biomarkers for Personalized Medicine
Radboud University Nijmegen Medical Centre (Dec 2011)
– Head Radboud Proteomics Center, co-chair Task Force Personalized Medicine
Radboud University Nijmegen (Nov 2009)
– Visiting Professor Molecular Profiling
Biomarkers, Molecular Profiling, Translational Medicine, Personalized Medicine
www.linkedin.com E alain.vangool@tno.nl, alain.vangool@radboudumc.nl T +31-6-11783031
4. TNO =
Netherlands Organisation for Applied Scientific Research
Mission = to drive ideas to reach their full market value.
We partner with:
Governmental & regulatory organisations
Universities
Pharma, chemical and food companies
International consortia
Knowledge
development
Knowledge
application
Knowledge
exploitation
Develop
fundamental
knowledge
With
universities
With
partners
With
customers
Embedded in the
market
TNO TNO Triskelion
4
Biomarker Europe Summit 2013, GTC BIO, Berlin
10 October 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
5. TNO
Facts &Figures:
Founded in 1932
Member of EARTO
Non-for-profit research institute
~3500 employees
19 sites in Netherlands
+ 18 sites/countries globally
Funding:
• Government (NL)
• Contract research (world)
• Public-private partnerships (world)
7 main themes
www.tno.nl
5
Biomarker Europe Summit 2013, GTC BIO, Berlin
10 October 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
6. TNO in European public-private partnerships
Healthy Living
Defence, Safety & Security
Transport & Mobility
Information Society
Industrial Innovation
Energy
Built Environment
Participation in EU projects:
(Jan 2013)
260 projects (3100 partners)
Roles of TNO:
Technical expertise
Focus on applications
PPP management skills
(in 10% role as coordinator)
32% success rate
(average FP7 is 21%)
Biomarker Europe Summit 2013, GTC BIO, Berlin
10 October 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
6
7. Year 1
Applying lessons learned across fields
Biomarker Europe Summit 2013, GTC BIO, Berlin
10 October 2013
Alain van Gool
e.g. System Biology @TNO
Year 2
Year 3
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
7
8. Radboudumc
• Mission: “To have a significant impact on healthcare”
• Strategic focus on Personalized Healthcare
• Core activities:
• Patient care
• Research
• Education
• 11.000 colleagues
• 50 departments
• 3.000 students
• 1.000 beds (ambition to close 500 by improving
healthcare)
• First academic centre outside US to fully implement EPIC
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
8
9. Radboudumc Technology Infrastructure
Preclinical Imaging Centre (PRIME) DTL
Microscopic Imaging Centre (MIC) DTL
Centre for Molecular and Biomolecular Informatics (CMBI) DTL
Genetics DTL
Centre for Proteomics, Glycomics and Metabolomics DTL
Centraal Dierenlaboratorium (CDL)
Clinical Research Centre Nijmegen (CRCN)
Radboud Biobank
Translationeel Malaria Onderzoek
Translational research and cellular therapy
Flow cytometry
Translational Neuroscience Unit (TNU)
Medical Innovation and Technology expert Centre (MITeC)
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
9
10. Centre for Proteomics, Glycomics & Metabolomics
Radboud
Proteomics
Center
Radboud
Metabolomics
Group
Radboud
Glycomics
Facility
Research Biomarkers Diagnostics
Mass spectrometry – NMR based, 16 dedicated fte, part of diagnostic laboratory (Department
Laboratory Medicine), close interaction with Radboudumc scientists and external partners
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
10
12. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Successes and failures in drug development
{Kola & Landis, Nat. Rev. Drug Disc. (2004) 8: 711}
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
12
13. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Limited view from the outside
Source: Gary Larson
Animal models Patient-related outcome
Source: National University Hospital Singapore
13
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
14. Key is to have a good view inside
High need for molecular tools that allow a look into the black box
and improve disease management: biomarkers
Drug exposure ?
Diagnosis ?
Cross-species differences ?
Patient classification ?
Prognosis ?
Target engagement ?
Modulation of mechanism ?
Off-target drug effects ?
Treatment Phenotype
Mechanism ?
Other (latent) diseases ?
Person
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
14
15. Biomarkers
{Biomarkers definition working group, 2001 }
Definition: ‘a characteristic that is objectively measured and evaluated as an
indicator of normal biological processes, pathogenic processes, or
pharmacologic responses to a therapeutic intervention’
Or ‘Whatever works in adding value’
Molecular biomarkers provide a molecular impression of a biological system
(cell, animal, human)
Biomarkers can be various sorts of data, or combinations thereof
15
Dutch CC meeting ‘Personalized Health Care”
Ede, 2 October 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
16. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
• Translational medicine
Exposure
Mechanism
Efficacy
Safety
• Personalized medicine
Diagnosis
Prognosis
Response
• Tools for data-driven decision making
Biologically relevant
Clinically accepted
Quantitative !
Different analytes/types
Fit-for-purpose application
16
Biomarker need in pharmaceutical drug development
{Source: Van Gool et al, Drug Disc Today 2010}
Pharma lead way
Nutrition and cosmetics copy
best practices
PharmaNutrition next big thing?
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
17. Biomarker-based translational medicine
Does the compound get to the site of action?
Does the compound cause its intended pharmacological/
functional effects?
Does the compound have beneficial effects on disease or
clinical pathophysiology?
What is the therapeutic window (how safe is the drug)?
How do sources of variability in drug response in target
population affect efficacy and safety?
Lead
Optimization
Exploratory
Development PoC
Lead
Discovery
Target
Discovery
Exposure ?
Mechanism ?
Efficacy ?
Safety ?
Responders ?
Start in Lead Discovery, complete in clinical Proof of Concept (one strategy)
{van Gool et al, Drug Disc Today 2010}
{Kumar, van Gool, in press 2013}
17
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
18. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Biomarker strategy: (data-driven) Decisions
To be made during testing of drug in preclinical and clinical disease models:
Target engagement? Effect on disease?
yes yes !
no no
• No need to test current
drug in large clinical trial
• Need to identify a more
potent drug
• Concept may still be
correct
• Concept was not correct
• Abandon approach
• Proof-of-Concept
• Proceed to full
clinical
development
“Stop early, stop cheap”
“More shots on goal”
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
18
19. Biomarker stakeholders in healthcare
19 EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
20. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
Personalized healthcare
20
HomeostasisAllostasisDisease
Time
Personalized health
Personalized medicine
“Health management”
Focus on resilience
“Disease management”
Focus on symptom(s)
Medical
treatment
or
Disease
Health
Non-health
21. The innovation gap in biomarker research & development
21
• Imbalance between biomarker discovery and application.
• Gap 1: Strong focus on discovery of new biomarkers, few biomarkers
progress beyond initial publication to multi-center clinical validation.
• Gap 2: Insufficient demonstrated added value of new clinical biomarker and
limited development of a commercially viable diagnostic biomarker test.
Discovery Clinical validation/
confirmation
Diagnostic
test
Number of
biomarkers
Gap 1
Gap 2
Dutch CC meeting ‘Personalized Health Care”
Ede, 2 October 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
22. Some numbers
22
Data obtained from Thomson Reuters Integrity
Biomarker Module, April 2013
Alzheimer’s Disease
Chronic Obstructive
Pulmonary Disease
Type II Diabetes Mellitis
Eg Biomarkers in time: Prostate cancer
May 2011: 2,231 biomarkers
Nov 2012: 6,562 biomarkers
Oct 2013: 8,358 biomarkers
EU: CE marking
USA: LDT, 510(k), PMA
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
23. The innovation gap in biomarker research & development
23
Discovery Clinical validation/
confirmation
Diagnostic
test
Number of
biomarkers
Gap 1
Gap 2
Dutch CC meeting ‘Personalized Health Care”
Ede, 2 October 2013
Alain van Gool
– Many new biomarkers are panels (RNA, protein, biochemical, imaging)
– Not wise to discover yet an other biomarker
– Focus on selecting the best biomarker (panels) among those already
found (scientific and patent literature, databases, etc)
– Develop those biomarkers tot clinically applicable tests
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
24. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Reasons for biomarker innovation gap
24
• Not one integrated pipeline of biomarker R&D
• Publication pressure towards high impact papers
• Lack of interest and funding for confirmatory biomarker studies
• Hard to organize multi-lab studies
• Biology is complex on organism level
• Data cannot be reproduced
• Bias towards extreme results
• Biomarker variability
• …
{Source: John Ioannidis, JAMA 2011} {Source: Khusru Asadullah, Nat Rev Drug Disc 2011}
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
25. Uptake of new biomarkers in healthcare
Research/technology push:
Biomarkers can and should provide the molecular part of this healthcare model in
monitoring and follow-up
Daily practice in clinical assessment:
Combination of personal opinion (patient and physician), physical examination, clinical
chemistry to generate personal profiles
New biomarkers are added where deemed useful by physician
Act accordingly in follow-up care (more or less personalized)
Medication (a.o. personalized medicine)
Nutrition (a.o. individualized diets)
Life style (a.o. individualized exercise, counseling)
Slow uptake of new biomarkers
Limited by careful / conservative attitude of clinicians (added value of new biomarker?)
Limited by reimbursement options by insurers (increasingly important)
25
World CDx Frankfurt
21 March 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
26. Personal profiles
Source: Barabási 2007 NEJM 357; 4}
• People are different
• Different networks influences
• Different risk factors
26
Dutch CC meeting ‘Personalized Health Care”
Ede, 2 October 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
27. BIODATA
PERSONALIZED
INTERVENTIONS
RISK FACTOR PATTERN
MOLECULAR LIFESTYLE / ENVIRONMENT
Metabolites RNA Protein
DNA Biochemical process
Enzymatic activity Imaging
mDNA Nutrition
Environment Social
network Attitude in life
Stress work / private
MULTIPARAMETER
PERSONAL PROFILES Statistics
Selection
Ranking
LIFESTYLE
NUTRITION
PHARMA
27
Dutch CC meeting ‘Personalized Health Care”
Ede, 2 October 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
28. Example personal profile-based patient assessment (1)
4 components:
1. Number of tender joints
2. Number of swollen joints
3. Acute phase reactants
(ESR or CRP in blood)
4. Patient’s self-assessment
Disease Activity Score (DAS) 28 composite outcome measure
On line calculator:
Formula: 0.56x(TEN28) + 0.28x(SW28) + 0.70ln(ESR) + 0.014(GH)
1.0 - 3.1: low disease activity
3.2 - 5.1: moderate disease activity
> 5.1: high disease activity
{www.das-score.nl}
28
Dutch CC meeting ‘Personalized Health Care”
Ede, 2 October 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
29. Example personal profile-based patient assessment (2)
{Chen et al, Cell 2012, 148: 1293}
Concept:
• Continuous monitoring (n=1)
• Routine biomarkers to alert
• Omics to explain
• Early intervention
29
Dutch CC meeting ‘Personalized Health Care”
Ede, 2 October 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
30. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Oncology
CVD, neuro, immune
Diabetes
Personal profiles differ per disease phenotype
30
Dutch CC meeting ‘Personalized Health Care”
Ede, 2 October 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
31. Companion Diagnostics
Right drug
in right patient
at right dose
at right time
In other words:
Apply a well characterized therapy in a biological system you know well
to treat a disease you understand well, in a way that you know works.
Use (molecular) biomarkers as diagnostic companions of a drug.
New: diagnostic companions to a person !
Dutch CC meeting ‘Personalized Health Care”
Ede, 2 October 2013
Alain van Gool
31
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
32. Companion Diagnostics – some numbers
At present in pharmaceutical development:
40.000 clinical trials ongoing
16.000 trials in oncology
8.000 trials in oncology have a companion diagnostic
At present on market:
113 Biomarker in drug label (2012; up from 69 in 2010 = +64%)
16 CDx testing needed (2012; up from 4 in 2010 = +400%)
Costs of development:
>1.000 MUSD per drug
~10 MUSD per diagnostic
Source: www.fda.gov
32
Dutch CC meeting ‘Personalized Health Care”
Ede, 2 October 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
33. Companion Diagnostics
Metabolism
Efficacy or
safety
Source: www.fda.gov
{Kumar and van Gool, 2013}
33
Dutch CC meeting ‘Personalized Health Care”
Ede, 2 October 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
34. Example Companion Diagnostics in Oncology
V600D/E
Kinase domain
{Roberts and Der, 2007}
B-RAFV600D/E mutation: constitutively active kinase, oncogenic addiction
Overactivate ERK pathway drives cell proliferation
RAF inhibitors block growth of tumor xenografts with B-RAFV600D/E mutation
Prevalence of B-RAFV600D/E
Melanoma (60%), colon (15%), ovarian (30%), thyroid (30%) cancer
Develop B-RAF inhibitors with B-RAFV600D/E as companion diagnostic
34
Dutch CC meeting ‘Personalized Health Care”
Ede, 2 October 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
35. 35
Clinical efficacy of Vemurafenib (PLX-4032, Zelboraf)
Key biomarkers:
Stratification: BRAFV600E mutation
Mechanism: P-ERK
Cyclin-D1
Efficacy: Ki-67
18FDG-PET, CT
Clinical endpoint: progression-free survival (%)
{Source: Flaherty et al, NEJM 2010}{Source: Chapman et al, NEJM 2011}
35
Dutch CC meeting ‘Personalized Health Care”
Ede, 2 October 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
36. 36
Clinical effects of Vemurafenib
{Wagle et al, 2011, J Clin Oncol 29:3085}
Before Rx Vemurafenib, 15 weeks Vemurafenib, 23 weeks
• Strong initial effects vemurafenib
• Drug resistancy
• Reccurence of tumors
36
Dutch CC meeting ‘Personalized Health Care”
Ede, 2 October 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
37. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
37
• BRAFV600D/E is considered the
driving mutation
• However, varying levels of
BRAFV600D/E mutation found in
regions of a primary melanoma
• Molecular heterogeneity in
diseased tissue
• Biomarker levels in tissue and
body fluids will vary
• New biomarkers are needed
• Challenge for companion
diagnostics
{Source: Yancovitz, PLoS One 2012}
Tumor tissue heterogeneity
Dutch CC meeting ‘Personalized Health Care”
Ede, 2 October 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
38. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Oncology
CVD, neuro, immune
Diabetes
Personal profiles differ per disease phenotype
38
Dutch CC meeting ‘Personalized Health Care”
Ede, 2 October 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
39. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
• Obesity
• Diabetes type 2
HEALTH DISEASE COMPLICATIONS
• Atherosclerosis
• Nephropathy fibrosis
• Osteoarthritis
• Stroke
• etc
Metabolic syndrome
metabolic disturbance local inflammation
Not a single cause but complex multifactorial diseases
Disturbed equilibrium between multiple pathways and key components
A system biology approach is needed
For discovery research, diagnosis and treatment
Continuous monitoring really pays off
Most effective therapy is ‘eat better, move more’ (lifestyle change)
Nutriceuticals / Lifestyle
Food
Pharma
39
Dutch CC meeting ‘Personalized Health Care”
Ede, 2 October 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
40. Overall scheme of metabolic disorder related processes
Myocardial
infactions
Heart
failure
Cardiac
dysfunction
dyslipidemia
Metabolically
healthy
High cholesterol High glucose Hypertension
Brain
disorders
NephropathyAtherosclerosis StrokeRetinopathy
Risk factors of the ‘metabolic syndrome’
Pathologies resulting from the ‘metabolic syndrome’
Visceral
adiposity
LDL elevated
Glucose toxicity
Fatty liver
gut
inflammation
endothelial
inflammation
systemic
Insulin resistance
systemic
inflammation
Hepatic IR
Adipose IR
Muscle metabolic
inflexibility
adipose
inflammation
Microvascular
damage
Myocardial
infactions
Heart
failure
Cardiac
dysfunction
Brain
disorders
Nephropathy
Atherosclerosis
β-cell failure
Reversible process
β-cell Pathology
High cholesterol
High glucose
gluc Risk factor
Hypertension
dyslipidemia
ectopic
lipid overload
Ìrreversible process
Hepatic
inflammation
Stroke
IBD
fibrosis
Retinopathy
Metabolically
healthy
{Nakatsuji, Metabolism 2009}{Source: Ben van Ommen, TNO}
41. Visceral
adiposity
LDL elevated
Glucose toxicity
Fatty liver
Gut
inflammation
endothelial
inflammation
systemic
Insulin resistance
Systemic
inflammation
Hepatic IR
Adipose IR
Muscle metabolic
inflexibility
adipose
inflammation
Microvascular
damage
Myocardial
infactions
Heart
failure
Cardiac
dysfunction
Brain
disorders
Nephropathy
Atherosclerosis
β-cell failure
High cholesterol
High glucose
Hypertension
dyslipidemia
ectopic
lipid overload
Hepatic
inflammation
Stroke
IBD
fibrosis
Retinopathy
Physical inactivity
Caloric excess
Chronic Stress
Disruption
circadian rhythm
Parasympathetic
tone
Sympathetic
arousal
Worrying
Hurrying
Endorphins
Gut
activity
Sweet & fat
foods
Sleep disturbance
Inflammatory
response
Adrenalin
Fear
Challenge
stress
β-cell Pathology
gluc Risk factor
Heart rate
Heart rate
variability
High cortisol
α-amylase
Systems view on (metabolic) health and disease
Lipids, alcohol, fructose
Carnitine, choline
Stannols, fibre
Low glycemic index
Epicathechins
Anthocyanins
Soy
Quercetin, Se, Zn, …
Metformin
Vioxx
Salicylate
LXR agonist
Fenofibrate Rosiglitazone
Pioglitazone
Sitagliptin
Glibenclamide
Atorvastatin
Omega3-fatty acids
Pharma
Nutrition
Lifestyle
{Source: Ben van Ommen, TNO}
42. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Comparing nutritional versus drug intervention
Age-matched “healthy” control group
t=16 w
(sampling)
t=9 wt=0
Induction of Diabetes intervention period
High-fat (HF) diet
High-fat diet “diseased” control group
Nutrition/Life style switch
HF + Drug 1
HF + Drug 2
HF + Drug 3
….HF + Drug 10
42
2ND intl Pharma-Nutrition Conference
Singapore, 17 April 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
43. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
clinicalchemistry
SystemnetworksMetabolomeTranscriptome
fluxes
Analysis: high throughput,
multi organ, multi level
High-end data mining and
warehousing
Extensive molecular phenotyping by ‘Omics’ analysis
43
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
44. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Effects on total adipose tissue weight
Full reversal of obese phenotype by ‘Lifestyle’ change, not by all drug treatments
T0901317 also reverses obese phenotype
44
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
45. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Effects on atherosclerosis
Still increased atherosclerosis in ‘Lifestyle’ group
T0901317 strongly induces atherosclerosis
45
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
46. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Each organ has its own
characteristics in
maintaining/loosing
flexibility and this
determines the
health to diabetes
transition.
{Nolan, Lancet 2011}
A sure need for system biology
High need to study the
effect of drugs/nutrition
on each of these organs
and their interaction
within the whole system
of each person.
46
Dutch CC meeting ‘Personalized Health Care”
Ede, 2 October 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
47. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
47
Working in complex human biological systems
requires a systems biology approach
Way forward:
1. Focus on key processes
2. Measure key node biomarkers
3. Convert to a functional fingerprint assay panel
4. Make actionable personalized decision on health /
disease management
5. Test added value in real life through field labs
48. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Important processes in
T2D
Diagnosis Potential interventions
Dietary/LS Pharma
1.Pancreatic β-cell function
(impaired insulin secretion)
*OGTT: I/ΔG and DI(0)
*PYY, Arg, His, Phe, Val, Leu
Lifestyle; β-cell
protective nutrients
(MUFA/isoflavonoids);
β -cell protective
medication (TZDs,
GLP-1 analogs,
DPP4-inhibitors)
2.Muscle insulin resistance
(decreased glucose uptake)
*OGTT: Muscle insulin resistance index,
Insulin secretion/insulin resistance index
*Val, Ile, Leu, Gamma-glutamylderivates,
Tyr, Phe, Met
PUFA/SFA balance;
Physical activity;
Weight loss;
TZDs (e.g.PPARγ)
3.Hepatic insulin resistance
(decreased glucose uptake and
increased hepatic glucose
production-HGP)
*Hepatic insulin resistance index *OGTT:
Hepatic insulin sensitivity index
*ALAT, ASAT, bilirubine, GGT, ALP, ck-18
fragments, lactate, α-hydroxybutyrate,
β-hydroxybutyrate
Decrease SFA and n-
6 PUFA, and increase
n-3 PUFA;
Weight loss;
Metformin;
TZDs;
Exenatide (GLP-1
analog);
DPP4 inhibitors
4. Adipocyte insulin resistance
and lipotoxicity
*basal adipocyte insulin resistance index
*FFA platform, glycerol
α-lipoic acid;
PUFA/SFA balance;
Omega 3 fatty acids;
Chitosan/plantsterols;
TZDs; Acipimox
5. GI tract (incretin
deficiency/resistance)
*ivGTT vs OGTT
*GLP-1, GIP, glucagon, galzuren
MUFA; Dietary fibre
(pasta/rye bread);
Exenatide
6. Pancreatic α-cell
(hyperglucagonemia)
*fasting plasma glucagon ? Glucagon receptor
antagonists;
Exenatide;
DPP4 inhibitors
7A.Chronic low-grade
inflammation in pancreas,
muscle, liver, adipose tissue,
hypothalamus
7B. Vascular inflammation
*CRP, total leucocytes
* V-CAM, I-CAM, Oxylipids, cytokines
Fish oil/n-3 fatty
acids; Vit. C/Vit.
E/Carotenoids;
Salicylates; TNF-α
inhibitors and others
48
Dutch CC meeting ‘Personalized Health Care”
Ede, 2 October 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
49. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Field labs: test health care concepts in real life
• Build field lab with pre-diabetic patients, physicians, dietitians, insurers, etc
• Measure individual ‘risk’ parameters for metabolic syndrome +/- challenge
• phenotypes, clinical chemistry, specific Omics, etc
• Convert data into a personal profile + personalized health advice
• life style +/- nutrition +/- pharmaceutical drugs
• Test personalized health concept in field lab following P4 medicine principle
• Alliance “Expedition Sustainable Care, starting with diabetes”
49
Dutch CC meeting ‘Personalized Health Care”
Ede, 2 October 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
50. Field labs: implementation in 1st line health care
• Implementation-plan ‘personalized diagnosis
of (pre)diabetic and their lifestyle treatment in
Dutch Health care’.
• Use of OGTT as a stratification biomarker for
subgroups of (pre)diabetic patients
• Use diagnosis for a tailored lifestyle
(and medical) treatment
for these subgroups
Being implemented in
1st line care
regio Hillegom
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
50
51. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Oncology
CVD, neuro, immune
Diabetes
Personal profiles differ per disease phenotype
51
Dutch CC meeting ‘Personalized Health Care”
Ede, 2 October 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
52. High attrition in most chronic diseases
{Source: Kola, 2008, Nature 83, 2: 227}
• Multifactorial causes of disease, mostly not well understood
• Risk factors include both molecular as lifestyle/environmental factors
• Treatment is often symptom-based, not mechanism-based
• System approach in diagnosis and treatment (systems medicine)
• Need improved disease definitions and understanding
52
Dutch CC meeting ‘Personalized Health Care”
Ede, 2 October 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
53. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Redefining disease
{Nature Reviews Drug Discovery 2011, 10: 641}
53
Underlying concept: a chronic disease = a collection of rare diseases
Dutch CC meeting ‘Personalized Health Care”
Ede, 2 October 2013
Alain van Gool
8th IMI call:
Joined effort in EU to improve disease definitions
and define best potential therapies
1. RA, SLE
2. AD, PD
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
54. From clinical Omics to personalized treatment:
• 12 families with liver disease and dilated cardiomyopathy (5-20 years)
• Initial clinical assessment didn’t yield clear cause of symptoms
• Specific sugar loss of serum transferrin identified via glycoproteomics
• Genetic defect in glycosylation enzyme identified via exome sequencing
• Outcome 1: Explanation of disease
• Outcome 2: Dietary intervention as succesful personalized therapy
• Outcome 3: Glycoprofile developed as diagnostic test by mass spectrometry
Personalized Health Care in rare diseases
Dietary
intervention
{Dirk Lefeber et al,
NEJM 2013}
54
Incomplete glycosylation Complete glycosylation
Dutch CC meeting ‘Personalized Health Care”
Ede, 2 October 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
56. The innovation gap in biomarker development
56
• Imbalance between biomarker discovery and application.
• Gap 1: Strong focus on discovery of new biomarkers, few biomarkers progress beyond
initial publication to multi-center clinical validation.
• Gap 2: Insufficient demonstrated added value of new clinical biomarker and limited
development of a commercially viable diagnostic biomarker test.
Discovery Clinical validation/
confirmation
Diagnostic
test
Number of
biomarkers
Gap 1
Gap 2
Dutch CC meeting ‘Personalized Health Care”
Ede, 2 October 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
57. Needed: A Biomarker Development Pipeline
57
• A focus on application of innovation, not on new technologies or biomarker discovery
• The innovation is a clinically validated biomarker that can be applied as diagnostic test
• Bring together available state-of-the art biomarker expertise in an industrial process flow
• Sponsors and end-users define objectives (a.o. pharma, diagnostics, patients)
• Shared biomarker R&D in Open Innovation Network based on Public-Private-Partnership
Shared knowledge,
technologies and objectives
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
58. Topsector LS&H - Roadmap Molecular Diagnostics
{www.rijksoverheid.nl}
{http://www.zonmw.nl/nl/roadmaps-lsh/}
Roadmap Molecular Diagnostics:
• Build an efficient biomarker development pipeline in Netherlands
• Bring all stakeholders together in a functional open innovation network
based on public-private-partnerships
• Have end-users (patients) direct biomarker discovery in beginning
• Improve progress of biomarkers from discovery to clinical implementation
9 TopSectors Multiple Roadmap teams per TopSector
58
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
59. Open Innovation Networks
(Next Generation Life Science)
59
(Source: Model TNO’s Holst Center)
Old New
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
60. Features of an Open Innovation Network
60
Pharma cies
Biobanks
Analytical
laboratories
Diagnostic cies
D
C
BA
Others
Access to a network of relevant scientists, reagents and technologies
Access to relevant markets and secondary networks
Flexible use of expertise and capabilities in network under standardised agreements
Funding for joined and bilateral projects
Accelerated translation of knowledge to innovation
C1
C2
C3
C..
Technology 1
Technology 2
Technology 3
Technology ..
Eg for biomarker R&D:
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
61. Biomarker Development Center
Concept
A functional public-private partnership network of multiple partners with strong
complementary biomarker expertise to develop innovative clinical biomarkers
to application, with a strong initial focus on pharmaceutical drug development
Pipeline
Biomarker Development
Center
Projects
A matrix network:
Pipeline: focus on improvement of available biomarker technologies
Projects: process well-defined biomarker development projects
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
61
62. Focus
Emerging
Discovery Clinical validation
and confirmation
Diagnostic
application
Number of
biomarkers
Experimental
Discovery
Assay kit
development
Assay
development
Early Late
Academia
(discovery)
Industry
(development)
Shared R&D in biomarkers:
1. Assay development of (diagnostic) biomarkers
2. Clinical biomarker validation (quantification/confirmation, multicenter)
Leading to standardised clinical applications
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
62
63. Biomarker Development Center (Netherlands)
STW perspectief application
Biomarker Development Center
Public-private partnership 4 years
Project budget 4.3M Eur
Close interactions with:
- Clinicians (biomarker application)
- Industry (+ 0.94MEur cash + 1.24MEur kind)
- Patient stakeholder associations
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
63
65. Biomarker Development Center (Europe)
• Open Innovation Network
• Joined effort by key partners
2013:
- Form consortium
- Plan development of disease-related
mechanistic biomarkers
- Secure initial funding (NL, private)
2014:
- Secure funding (IMI2, Horizon2020, COST)
- Run projects for showcases
- Expand with projects on shared biomarker
interests
- Expand to USA, Canada
65
+ >30 partners
65
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
67. Personalized Healthcare by Food + Lifestyle + Pharma
67
Dutch CC meeting ‘Personalized Health Care”
Ede, 2 October 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
68. Acknowledgements
Jan van der Greef
Ben van Ommen
Peter van Dijken
Robert Kleemann
Lars Verschuren
Bas Kremer
Ton Rullmann
Marijana Radonjic
Thomas Kelder
Suzan Wopereis
and others
Ron Wevers
Jolein Gloerich
Dirk Lefeber
Monique Scherpenzeel
Leo Kluijtmans
Udo Engelke
and others
Lutgarde Buydens
Jasper Engel
Lionel Blanchet
Jeroen Jansen
and others
Radboud UMC Personalized Healthcare Taskforce:
Andrea Evers, Alain van Gool, Joris Veltman, Jan Kremer, Bas
Bloem, Maroeska Rovers, Jack Schalken, Paul Smits + Gerdi
Egberink, Viola Peulen, Martijn Hoogboom, Martijn Gerretsen
68
alain.vangool@tno.nl
alain.vangool@radboudumc.nl
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool