dr. S.A. (S.A.) Fuchs
dr. S.A. (S.A.) Fuchs
- Metabolic diseases patient care
I am a pediatrician in metabolic diseases and associate professor at the UMC-Utrecht. After living in France for 4 years (Lycée International, St Germain-en-Laye), I finished secondary school at the St. Maartenscollege, Maastricht (gymnasium, cum laude). For 1 year, I studied Spanish in Granada (Colegio Nueva Universidad de Granada), followed by pharmacy (doctoral & postdoctoral; cum laude) and medicine (doctoral & postdoctoral; cum laude) at the University of Utrecht, including a 6-month research project in Edinburgh (prof. Webb) and an internship in Boston (Harvard Medical School). I combined pediatric training with a PhD in metabolic diseases (UMC-Utrecht; ZonMW AGIKO grant), and received 3 children (2005, 2007, 2009). Subsequently, I specialized in metabolic/genetic diseases, while setting up my own research-line (ZonMW Klinische Fellows grant). I now combine my work as a pediatrician in metabolic diseases with a PI position in the RMCU (Hubrecht Institute). My research group currently consists of 1 postdoc researcher, 9 PhD-students, 1 technician and several master students. My research is supported by numerous grants (including the ERC Starting Grant), prestigious prizes (including the Elisabeth von Freyburg penning (2016), and talent programs (Eureka Certificate Course 2011, Leading Ladies program 2013-2019, Steyn Parvé program 2018-2019).
As a pediatrician in metabolic diseases, I am painfully aware of the limitations in care for our patients. Trained as a pharmacist and pediatrician, working as a scientist in a prestigious science park and a clinician in an academic hospital, facilitated for innovative treatment strategies, and living in a time of unprecedented technological possibilities, I am in a unique position to pursue my ambition to improve care for patients with rare genetic/metabolic diseases.
Implementation of metabolic diseases in the neonatal screening program enables early detection and treatment to prevent irreversible damage, but also yields novel patient cohorts, with unknown clinical phenotypes. As the national NFU-acknowledged expertise center for long chain fatty acid oxidation disorders, my group performs standardized national follow-up in our multidisciplinary 1-day diagnostic/follow-up facility (Sylvia Toth Center) to better interpret novel “screening-mutations”. We develop innovative exercise tests to provide individualized exercise protocols for all Dutch patients >6 years and prepare to test ketone drinks to improve muscle function and general condition (PhD-student M.S., Metakids grant) in collaboration with Visser (UMCU) & Houtkooper/Wanders (Amsterdam UMC).
Diagnostic use of whole exome sequencing unveils many (novel) genetic diagnoses and variants of unknown significance. To understand functional consequences, we analyze genomic results, perform (un)targeted assays in patient-derived materials (body fluids, cells, organoids), and deep phenotype the patients (PhD-student I.M., Metakids and WKZ grants) in collaboration with our metabolic (vHasselt/Verhoeven) and genomics (vGassen/Mokry/vBoxtel) facilities.
To perform these assays, I set up liver organoid technology in our lab in collaboration with the Clevers-group. We keep optimizing our protocols to improve hepatic modeling (PhD-students I.J. and I.A, ZonMW TAS, UMD grants), also exploring liver biofabrication in collaboration with Spee (UU) (PhD-student V.L., NWO-TTW grant). We also generate organoids from other organs, including intestine and endometrium (PhD-student B.B. in collaboration with the gynecology department (UMCU: Broekman, Leuven: Vankelecom)). I have generated a biobank for biological material (including organoids, fibroblasts, body fluids) from currently >200 patients, suspected of genetic/metabolic disease (Metabolic Biobank 19-489).
We set up functional assays in organoids (PhD-student I.S., Metakids, MLDS grants, patient-funding) to study energy metabolism in collaboration with Houtkooper/Wanders (Amsterdam UMC); bile salt excretion and polarity with vdWoerd/Houwen (UMCU), vdGraaf (Amsterdam UMC); diseases in protein translation with Vos (UMCU), Tanenbaum (Hubrecht Institute) and Agami (NKI), and drug metabolism with Huch/Gehart (ERC proof-of-concept grant).
These functional assays enable personalized treatment testing. For diseases in protein translation (ARS-deficiencies), we developed a fibroblast amino acid sensitivity assay, generating insight in the disease mechanism and treatment possibilities. Subsequently, we treated 8 patients with beneficial results (PhD-student G.K., Metakids grant) in collaboration with vKarnebeek/Salomons (Amsterdam UMC). We are now applying for an NFU-recognized expertise center for ARS-deficiencies and perform fibroblast analyses for many (inter)national ARS-deficient patients.
Using functional assays in patient-derived organoids, we test compounds correcting general molecular mechanisms (read-through agents, protease inhibitors, protein folding correctors, mRNA) (postdoc M.K., Elisabeth von Freyburg grant) in collaboration with Beekman (RMCU). Using our energy metabolism assays, we test (dietary) interventions (PhD-student I.M., Metakids grant) in collaboration with the Hoeijmakers-group (PMC), and mitochondrial transplantations (PhD-student A.O, Tjallingh Roorda grant) in collaboration with McCully (Harvard Medical School).
As an innovative treatment strategy, I prepare to use allogenic and gene-corrected autologous organoids for first-in-human liver organoid transplantations (PhD-students I.J. and I.A., ZonMW TAS) in collaboration with Clevers (Hubrecht Institute), Spee (UU), Bredenoord (UMCU, parallel ethical research, ZonMW Ethiek&Gezondheid grant), vBoxtel (PMC). In parallel, I aim to develop a systemic in vivo gene correction program targeting the liver.
To inspire (clinician-)scientists to perform research with impact on patients/society, I was chair (2013-2015), member of the Board (2015-2019) and Advisory Board (since 2019) of TULIPS (Training Upcoming Leaders In Pediatric Science), I organized the Utrecht Translational Medicine Summer School (Organizing Committee-member since 2016), and I am member of the Program Committee (since 2019) and Strategic Team (since 2020) of the EUREKA Certificate Program for Translational Medicine.
2022 Member of jury Prijs voor de Jonge Onderzoeker (NVK)
2021 - now Selection member of the TULIPS – Auxilium & Caritas Award
2021 Informative talk with Ultragenyx about trial for patients with long chain fatty acid oxidation disorder (no payment)
2020 - now Remote reviewer for ERC advanced grant 2020
2020 – now Member of the Strategic Team of the EUREKA Certificate Program for Translational Medicine, Siracusa, Italië (http://eurekainstitute.org/)
2020 - now Member of the UMC Utrecht Open Science-Team
2019 – now Member of the Advisory Board of TULIPS (Training Upcoming leaders in Paediatric Science), an organization devoted to improving child health by empowering young clinician scientists to achieve high quality research
2019 – now Member of the Program Committee of the EUREKA Certificate Program for Translational Medicine, Siracusa, Italië (http://eurekainstitute.org/)
2018 – now Participant in the national initiative “United for Metabolic Diseases” (UMD), member of work package “innovative treatments & treatment outcomes”
2018 - now Member of the Selection Committee of the NVK young investigators award
2018 - now Member of the Selection Committee for the Child Health boost grant
2017 – now Research Coördinator of the departments metabolic diseases, gastroenterology/ hepatology, endocrinology and nephrology (UMCU)
2015 – now Organizing Committee of the Utrecht Translational Medicine Summerschool – Eureka Institute and Science in Transition (course 2016, 2017 and 2018)
2013 – now Member of the educational review board evaluating metabolic training facilities in metabolic centres in the Netherlands
2016 Creation of the E-learning module Translational Medicine (together with dr. S. Brugman) for EUREKA Certificate Program for Translational Medicine
2018 – 2019 Selected member of the Elisabeth Steyn Parvé female talent program of the UMC Utrecht
2013 – 2019 Participant of the Leading Ladies Program, a prestigious program encouraging talent development for 5 selected female clinician-scientists in the WKZ-UMC
2015 – 2019 Board member of TULIPS
2013 – 2015 Chair of the board of TULIPS
2012 Member of SSIEM (Society for the Study of Inborn Errors of Metabolism
2012 Member of NVK (Nederlandse Vereniging voor Kinderartsen)
2012 Member of ESN (Erfelijke Stofwisselingsziekten Nederland)
2010 Selected participant of the EUREKA Certificate Program for Translational Medicine, Siracuse, Italy
Fellowship and Awards
2021 50.000 € Grant: Centaur
2021 1.500.000 € ERC Starting Grant: PRIME Prime editing to Repair Inborn Metabolic Errors
2021 15.000 € Child Health Boost grant: Broadening the scope of prime editors for efficient correction of untreatable cystic fibrosis mutations (PhD-student IS/me)
2021 18.531 € voor onderzoek naar metabole ziekten (S.A. Fuchs)
2020 ESN-Stimulerings prijs (to PhD-student Gautam Kok)
2020 Tjallingh Roorda Stichting: Mitochondrial transplantation as a novel therapy for patients with mitochondrial disease
2020 Metakids / UMD: Energising patients with inherited metabolic diseases
2020 Metakids / UMD:Improving hepatic engraftment by generating adult hepatocyte organoid cultures
2019 Metakids / UMD: New ways, better outcomes: n-of-1 for all
2019 Metakids / UMD: The promise of messenger RNA as treatment approach for inborn errors of metabolism: advancing tissue targeting
2019 Elisabeth von Freyburg Stichting: Better Care for the Rare – nieuwe behandelingen testen in mini-organtjes van patiënten met genetische ziekten
2019 Metakids / PNOzorg: Elk kind moet kunnen sporten, ook kinderen met een ziekte in de vetafbraak
2018 Klokhuis wetenschapsprijs (nomination, 2e prize)
2017 Open Technologieprogramma: Biofabrication of liver constructs for hepatotoxicity testing and personalized medicine approaches (Co-applicant, Main applicant: Spee)
2016 ERC proof of concept grant: Toxanoid: pharmacological safety testing in human adult stem cell-derived organoids (Co-applicant, Main applicant: Gehart)
2016 Metakids Research Funding / Vriendenloterij: Naar een nieuw onderzoeksmodel voor stofwisselingsziekten
2016 Elisabeth von Freyburg penning, prize for young promising internationally recognized researcher
2015 MLDS Subsidie: Liver organoids as a unique patient derived in vitro model to study ATP8B1 deficiency and test novel therapeutic strategies
2015 Stofwisselkracht: Liver stem cells for treatment of metabolic diseases
2015 Metakids Research Funding: Towards a new in vitro model for inborn errors of metabolism
2015 ZonMW Ethiek en Gezondheid: The ethics of first in human organoid transplantation (Co-applicant, Main applicant: Bredenoord)
2014 ZonMW Klinische Fellows: Stem cell based strategies for patients with liver disease
2013 ESN stimulating prize: for innovative research into inherited liver diseases
2013 Metakids Research Funding: Lever stamcel transplantatie – nieuwe behandelmogelijkheid voor metabole ziekten?
2013 Leading Ladies WKZ Fund
2011 ZonMW TAS: Regenerating Intestinal Tissue with Stem cells (RITS); since 2014 redirected towards liver stem cell research; main applicant S. Middendorp to S. Fuchs
2004 NWO (ZONMW)-AGIKO stipendium (920-03-345): de rol van D-serine in perinatale asfyxie; een nieuwe kandidaat voor farmacologische interventie?
Research Output (61)
Ardisasmita Arif Ibrahim, Schene Imre F, Joore Indi P, Kok Gautam, Hendriks Delilah, Artegiani Benedetta, Mokry Michal, Nieuwenhuis Edward E S, Fuchs Sabine A 14 Oct 2022, In: Communications biology. 5
Veenvliet Annemarijne R J, Garrelfs Mark R, Udink Ten Cate Floris E A, Ferdinandusse Sacha, Denis Simone, Fuchs Sabine A, Schwantje Marit, Geurtzen Rosa, van Wegberg Annemiek M J, Huigen Marleen C D G, Kluijtmans Leo A J, Wanders Ronald J A, Derks Terry G J, de Boer Lonneke, Houtkooper Riekelt H, de Vries Maaike C, van Karnebeek Clara D M Jun 2022, In: Molecular Genetics and Metabolism Reports. 31
Kok Gautam, Verstegen Monique Ma, Houwen Roderick Hj, Nieuwenhuis Edward Es, Metselaar Herold J, Polak Wojciech G, van der Laan Luc Jw, Spierings Eric, den Hoed Caroline M, Fuchs Sabine A 25 Apr 2022, In: Liver Transplantation. 28 , p. 1356-1366 11 p.
Schwantje Marit, Ebberink Merel S., Doolaard Mirjam, Ruiter Jos P.N., Fuchs Sabine A., Darin Niklas, Hedberg-Oldfors Carola, Régal Luc, Donker Kaat Laura, Huidekoper Hidde H., Olpin Simon, Cole Duncan, Moat Stuart J., Visser Gepke, Ferdinandusse Sacha 11 Apr 2022, In: Journal of Inherited Metabolic Disease. 45 , p. 819-831 13 p.
Schwantje Marit, Fuchs Sabine A., de Boer Lonneke, Bosch Annet M., Cuppen Inge, Dekkers Eugenie, Derks Terry G.J., Ferdinandusse Sacha, Ijlst Lodewijk, Houtkooper Riekelt H., Maase Rose, van der Pol W. Ludo, de Vries Maaike C., Verschoof-Puite Rendelien K., Wanders Ronald J.A., Williams Monique, Wijburg Frits, Visser Gepke 5 Apr 2022, In: Journal of Inherited Metabolic Disease. 45 , p. 804-818 15 p.
Schene I F, Joore I P, Baijens J H L, Stevelink R, Kok G, Shehata S, Ilcken E F, Nieuwenhuis E E S, Bolhuis D P, van Rees R C M, Spelier S A, van der Doef H P J, Beekman J M, Houwen R H J, Nieuwenhuis E E S, Fuchs S A 1 Mar 2022, In: Nature Communications. 13
Evers Martijn J W, Du Wenjuan, Yang Qiangbing, Kooijmans Sander A A, Vink Arjan, van Steenbergen Mies, Vader Pieter, de Jager Saskia C A, Fuchs Sabine A, Mastrobattista Enrico, Sluijter Joost P G, Lei Zhiyong, Schiffelers Raymond 22 Jan 2022, In: Journal of controlled release : official journal of the Controlled Release Society. 343 , p. 207-216 10 p.
Mijnders Marjolein, Fuchs Sabine A, Nieuwenhuis Edward E S 12 Jan 2022, In: Nederlands Tijdschrift voor Geneeskunde. 166
Ravel Jean-Marie, Dreumont Natacha, Mosca Pauline, Smith Desiree E C, Mendes Marisa I, Wiedemann Arnaud, Coelho David, Schmitt Emmanuelle, Rivière Jean-Baptiste, Tran Mau-Them Frédéric, Thevenon Julien, Kuentz Paul, Polivka Marc, Fuchs Sabine A, Kok Gautam, Thauvin-Robinet Christel, Guéant Jean-Louis, Salomons Gajja S, Faivre Laurence, Feillet François Dec 2021, In: Human mutation. 42 , p. 1576-1583 8 p.
Kok Gautam, van Karnebeek Clara D M, Fuchs Sabine A 5 Nov 2021, In: Genetics in medicine : official journal of the American College of Medical Genetics. 24 , p. 506-507 2 p.