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Cargo-Specific Role for Retriever Subunit VPS26C in Hepatocyte Lipoprotein Receptor Recycling to Control Postprandial Triglyceride-Rich Lipoproteins

November 21, 2022|Publications|

Dyonne Y. Vos, Melinde Wijers, Marieke Smit, Nicolette Huijkman, Niels J. Kloosterhuis, Justina C. Wolters, Joël J. Tissink, Amanda C.M. Pronk, Sander Kooijman, Patrick C.N. Rensen, Jan Albert Kuivenhoven and Bart van de Sluis

About Metabolic Syndrom

Metabolic syndrome (MetS) is a collection of pathological conditions that include abdominal obesity, increased blood pressure, insulin resistance and increased blood glucose and lipids. MetS is a risk factor for type 2 diabetes (T2D), non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD). Combined, these cardio-metabolic diseases form a heavy burden on our society and health care system. Clearly, increasing our knowledge on the molecular mechanisms contributing to the maintenance of metabolic homeostasis will provide tools to improve prognosis, diagnosis and ultimately treatment of patients with cardio-metabolic diseases.

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About Metabolic Syndrom

Metabolic syndrome (MetS) is a collection of pathological conditions that include abdominal obesity, increased blood pressure, insulin resistance and increased blood glucose and lipids. MetS is a risk factor for type 2 diabetes (T2D), non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD). Combined, these cardio-metabolic diseases form a heavy burden on our society and health care system. Clearly, increasing our knowledge on the molecular mechanisms contributing to the maintenance of metabolic homeostasis will provide tools to improve prognosis, diagnosis and ultimately treatment of patients with cardio-metabolic diseases.

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Mission & Ambition

It is the ambition of EndoConnect to bring top scientists and industrial partners from different European countries (the Netherlands, Germany, UK, Finland, Spain, Switzerland) together to train PhD students in interdisciplinary research, with the focus on translating key findings from cellular and animal models to patients with cardio-metabolic diseases.
EndoConnect will provide an international training program for PhD students to acquire knowledge and state-of-the-art scientific, technical, and transferable skills to connect molecular and cell biology research with physiology and biomedical research towards translation. This training will significantly increase the career perspectives of PhDs and allow them to become the future leaders in this emerging interdisciplinary field, both in a scientific and societal manner.

Work Packages

Our Team

Principal investigators & management

Project Coordinator; University Medical Center Groningen, NL

Bart van de Sluis

Project Manager

Floor Morriën

University of Bristol, UK

Pete Cullen

University Medical Centre Utrecht, NL

Judith Klumperman

Helmholtz Institute, Munich, DE

Anja Zeigerer

University Medical Center Hamburg-Eppendorf, DE

Jörg Heeren

University Medical Center Groningen, NL

Jan Albert Kuivenhoven

Institute D' Investigacions Biomèdiques August Pi i Sunyer, Barcelona, ES

Albert Pol

University Medical Center Hamburg-Eppendorf, DE

Pablo Sáez

AstraZeneca, UK

Helen Boyd

AstraZeneca, UK

Kevin Moreau

University of Helsinki, FIN

Elina Ikonen

Academic Medical Centre Amsterdam, NL

Noam Zelcer

Nebion, CH

Philip Zimmermann

Utrecht University, NL

Alain de Bruin

Institute D' Investigacions Biomèdiques August Pi i Sunyer, Barcelona, ES

Marta Bosch

University Medical Centre Utrecht, NL

Raymond Schiffelers

Project Coordinator; University Medical Center Groningen, NL

Bart van de Sluis

Dr. Bart van de Sluis graduated in Biology from the Utrecht University, the Netherlands. In 1998, he was appointed as a PhD student at the Department of Human Genetics at the Utrecht University, the Netherlands. He received his PhD degree (cum laude, highest distinction in the Netherlands) in 2002. As a post-doctoral fellow, he continued his scientific career at the Genetics and Molecular Biology Branch at the National Human Genome Research Institute (NIH, Bethesda, USA). Mid-2004, he returned back to Utrecht as a post-doc and in March 2008, he moved to Groningen to set up his own research group to further understand the molecular regulation of lipid metabolism. He is using cellular and mouse models to study these different processes in great detail. In addition, he runs a mouse transgenic mouse facility at the RUG/UMCG to generate new mouse models using different approaches, such as the CRISPR/Cas9 methodology. 

Project Manager

Floor Morriën

Floor works as a project manager at UMCG Research BV. She is involved in the post-award project management of several EU projects including MSCA Innovative Training Networks.

University of Bristol, UK

Pete Cullen

Prof. Peter Cullen is Professor of Biochemistry, Wellcome Trust Investigator and Medical Research Council Programme Grant Holder with the School of Biochemistry at the University of Bristol. With over 20 years of running an independent laboratory he has supervised 13 PhD students to completion. The vast majority are continuing to develop their careers as group leaders, post-docs in academic and industry, or through positions within funding agencies and medical publishing/writing.

University Medical Centre Utrecht, NL

Judith Klumperman

Judith Klumperman is cell biologist and expert in electron microscopy (EM). Her lab is internationally renowned for the use of immuno-EM and correlative light electron microscopy (CLEM). Her research is aimed to understand how genetic mutations lead to cellular disorganization and disease with focus on the endo-lysosomal pathway. Since 2018, Judith chairs the Netherlands Electron Microscopy Infrastructure’ (NEMI) for national coordinated investments in EM development, infrastructure and education.

Helmholtz Institute, Munich, DE

Anja Zeigerer

The research group leader Anja Zeigerer is functioning as PI in this project. Dr. Zeigerer conducted her PhD at Weill Cornell Medical School, NYC and obtained her degree at the University of Heidelberg in 2004. She moved on to do a first postdoc at Rockefeller University, NYC afterwards and a second one to the Max-Planck-Institute for Cell Biology and Genetics, Dresden. Now she is leading her independent research group since 2015 at the IDC in Munich.

University Medical Center Hamburg-Eppendorf, DE

Jörg Heeren

Prof. Dr. Joerg Heeren (born 1970) is Heisenberg Professor for Immunometabolism, deputy director of the Department of Biochemistry and Molecular Cell Biology at UKE. He has great experience as principal investigator in national and international collaborative research initiatives. The consortium will benefit from his expertise in metabolic studies including nanoparticle-based imaging technologies, technologies to analyse systemic and organ-specific energy metabolism, and high-throughput platform technologies to monitor organ-specific metabolomics networks in adipose tissue.

University Medical Center Groningen, NL

Jan Albert Kuivenhoven

Started out as a molecular and cellular biologist (MSc 1991 cum laude; Wageningen University Research Center, the Netherlands). He finished his PhD at the Academic Medical Center, University of Amsterdam (1996; Department of Experimental Vascular Medicine) on the genetics of high-density lipoprotein and triglyceride metabolism. Following a post-doc at the Department of Biology, Massachusetts Institute of Biology, Boston (1997-1999), where he worked on angiogenesis, he returned to Amsterdam and continued working on the genetics of human dyslipidemias. In September 2011, he moved to the University Medical Center Groningen (Department of Pediatrics) where he is heading a basic research group with strong translational focus on identification and molecular characterization of new genes with roles in lipid and lipoprotein metabolism. As of 2017, he has been appointed full Professor at the University Medical Center Groningen.

Institute D' Investigacions Biomèdiques August Pi i Sunyer, Barcelona, ES

Albert Pol

The Lipid Trafficking and Disease group, supervised by Albert Pol, was founded in 2001 to characterize the cellular processes regulated or altered due to lipid accumulation within cells and how these processes determine animal’s physiology and human disease. 

University Medical Center Hamburg-Eppendorf, DE

Pablo Sáez

Prof. Dr. Pablo J. Sáez (born 1984), recently appointed in the Department of Biochemistry and Molecular Cell Biology at UKE. He has a large international network of collaborators due to his international training. His main expertise is in cell communication and cell migration using novel techniques (i.e. microfluidics and micropatterning). The consortium will benefit from his expertise on lyososomal calcium channels, as well as his expertise in cell signaling (ER-stress) induced by obesity.

AstraZeneca, UK

Helen Boyd

Helen Boyd is a biochemist and has worked in the pharmaceutical industry for over 25 years. This has involved working as a laboratory scientist, a scientific team leader and more recently in business planning and operations. Helen has supervised a number of PhD students, post-doctoral scientists and has published over 20 peer review papers.

AstraZeneca, UK

Kevin Moreau

Kevin Moreau is the PROTAC safety leader at AstraZeneca. Before joining AstraZeneca, Kevin was a Principal Investigator at the University of Cambridge, UK. Kevin is a protein trafficking expert, having worked on protein degradation for more than 10 years, notably in the autophagy-lysosomal field. Kevin has published more than 25 peer review papers including papers in Cell, Nature Cell Biology, Journal of Cell Biology and Nature Communications.

University of Helsinki, FIN

Elina Ikonen

Professor Elina Ikonen, MD PhD, leads the Lipid Trafficking Lab at the Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki. She is the Chair of the HiLIFE BioImaging platform, Director of the Biomedicum Imaging Unit, EMBO member and European Coordinator of Foundation Leducq Transatlantic Network of Excellence in Cellular and systemic cholesterol transport in physiology and disease. She has previously supervised 15 postdoctoral fellows and 12 PhD theses into completion.  

Academic Medical Centre Amsterdam, NL

Noam Zelcer

The local PI, Prof dr Noam Zelcer leads an independent research group in the Department of Medical Biochemistry of the AMC (5 PhDs, 3 Postdoc, and 3 technician) and is a holder of an ERC Consolidator grant, an NWO Vici grant, and is an Established Investigator of the Dutch Heart Society. He puts great emphasize on mentoring his trainees and facilitating their growth towards scientific independence. 

Nebion, CH

Philip Zimmermann

Philip Zimmermann studied agronomy at ETH Zurich, performed a PhD in molecular biology and a post-doc in bioinformatics at ETH Zurich. After this post-doc he became oberassistant at ETH Zurich where he started the development of the Genevestigator platform. In 2008 NEBION was founded as a spin-off company where Philip currently is CEO.

Utrecht University, NL

Alain de Bruin

Alain de Bruin is the head of department Biomolecular Health Sciences at the Faculty of Veterinary Medicine. He obtained his DVM degree in 1994 at University of Hannover, Germany. He performed his PhD research in the field of cancer biology and graduated in 1999 at the University of Berne, Switzerland. From 1999-2005, he was a veterinary anatomic pathology resident and postdoctoral fellow at the Ohio State University, USA. In 2005 he was appointed as full Professor in Pathobiology at Utrecht University.

Institute D' Investigacions Biomèdiques August Pi i Sunyer, Barcelona, ES

Marta Bosch

Marta Bosch is the senior associate researcher at the Lipid Trafficking and Disease group, headed by Albert Pol. Her research is involved in the study of the cellular processes related to lipid homeostasis, lipid droplet and mitochondrial physiology and energetic metabolism. Since early this year, she has been appointed Tenure-eligible lecturer in the Department of Biomedical Sciences at the University of Barcelona

University Medical Centre Utrecht, NL

Raymond Schiffelers

Raymond Schiffelers is pharmaceutical scientist in the field of nanomedicine. His lab focuses on synthetic and natural lipid-based nanoparticles for the delivery of nucleic acids and small molecular weight drugs. This involves the design and characterization of these formulations, their cellular interaction up to therapeutic efficacy. Raymond is presidentof  the European Technology Platform Nanomedicine and is part-time employed as vice-president preclinical R&D at Nanocell Therapeutics a start-up in the field of gene engineering.

PhD students

University of Bristol, UK

Shrestha Shaw

University of Bristol, UK

Rebeka Butkovic

AstraZeneca, UK

Camilla Ruffilli

University Medical Centre Utrecht, NL

Matteo Tantucci

Academic Medical Centre Amsterdam, NL

Klevis Ndoj

Helmholtz Institute, Munich, DE

Carmen Paredes Yubero

Institute D' Investigacions Biomèdiques August Pi i Sunyer, Barcelona, ES

Gyana Lipsa Parida

Helmholtz Institute, Munich, DE

Joël Tissink

University of Utrecht, NL

Orsolya Farkas

University Medical Center Groningen, NL

Ankia Visser

University Medical Center Hamburg-Eppendorf, DE

Kim Hurkmans

University Medical Center Hamburg-Eppendorf, DE

David McGrath

UMCU, Utrecht, NL

Alejandra Puentes

University of Helsinki, FI

Haoran Li

University Medical Center Groningen, NL

Markus Barbosa

University of Bristol, UK

Shrestha Shaw

Shrestha completed her Integrated BSc-MSc degree from Indian Institute of Science Education and Research (IISER) Mohali. She was actively a part of wet lab for three years where she basically worked on the roles of small GTPases in regulating endocytic traffic towards lysosomes. Her Master’s thesis was on role of an effector of small G-protein in retrograde trafficking of CI-MPR receptor from early endosomes to Golgi. All these experiences motivated her to continue working in the field of endocytic trafficking and be a part of EndoConnect. Currently, she is pursuing a PhD at University of Bristol, UK, in Pete Cullen’s lab, during which she is hoping to unravel the structural assembly of multi-protein complexes like CCC and Retriever which plays an essential role in endosomal cargo sorting. 

University of Bristol, UK

Rebeka Butkovic

Rebeka started her studies with a BSc in Microbiology at the University of Ljubljana, Slovenia. Her interest in cell biology led her to study Genetics and Molecular Biosciences at the University of Helsinki, Finland. During her Master’s there, she specialised in Cell and Developmental biology, and her research projects focused on the crosstalk between different organellar systems. She is eager to continue studying the endo-lysosomal system and she is very excited to be a part of EndoConnect. In her PhD project at the University of Bristol, she is focusing on a complex called Retriever, and on its function in hepatocytes.  

AstraZeneca, UK

Camilla Ruffilli

Camilla completed her BSc in Biotechnologies in Bologna, Italy and during her time there she undertook a placement at the anatomy department. In 2020 she completed her MSc with an internship at the Institute of Cancer Research (ICR) in London, focusing on cellular biology and new molecular tools such as the splitFAST reporter system. She is thrilled to have started her PhD in collaboration with AstraZeneca in Cambridge and for the first time experience research at an industrial setting. She will be working with PROTACs, chimeras that induce selective protein degradation, which she will then use to target specific cell surface receptors. She also looks forward to enjoying some warm scones with English tea!

University Medical Centre Utrecht, NL

Matteo Tantucci

Matteo obtained his double master degree in Functional Genomics and Molecular and Cellular biology from the university of Trieste and Rennes1, respectively. During his internship at the IPNP in Paris, he worked on the development of an optogenetic tool to study exosome secretion and the relationship between the endosomal system and cholesterol. In September 2021 he joined Klumperman’s lab at UMC Utrecht as a PhD student to investigate the role of Vps3, Vps8 and Vps33B in cholesterol metabolism, with a focus on LDLR/LRP1 transport. In his free time he likes to play chess and watch old movies.  

Academic Medical Centre Amsterdam, NL

Klevis Ndoj

Klevis obtained his MSc in Medical and Pharmaceutical Biotechnology at University of Florence in May 2021. He did his master internship at The Institute for the Study, Prevention and Oncology Network (ISPRO), applying CRISPR genetic screening to find novel regulators of genetic editors AID/APOBECs family. In line with his scientific interest and expertise, he joined the Noam Zelcer group as a PhD student in July 2021. Here, in collaboration with the EndoConnect network, his main focus is to elucidate the role of NPC1 in LDL-derived cholesterol transport from the late Endo-Lysosomal compartment.   

Helmholtz Institute, Munich, DE

Carmen Paredes Yubero

Carmen comes from Madrid, Spain. She has a Bachelor’s Degree in Biochemistry and a Master’s Degree in Biomedicine from Autonomous University of Madrid. During these studies, she was part of a couple of research projects focused on understanding the role of different mitochondrial DNA haplotypes in the function of the electron transport chain and the production of reactive oxygen species. She recently started her PhD project at Anja Zeigerer’s lab at Helmholtz Zentrum München, where she will focus on studying the role of candidate endosomal proteins in metabolism.  

Institute D' Investigacions Biomèdiques August Pi i Sunyer, Barcelona, ES

Gyana Lipsa Parida

Gyana holds an integrated bachelor’s and master’s dual degree from the Indian Institute of Science Education and Research,Mohali, India. She majored in biological sciences from the institute and was closely associated with several labs doing internships and a research based master’s degree course. During her master’s thesis she worked actively in the field of cell biology focusing on characterization of the interaction of the protein TECPR2 with multisubunit tethering factor HOPS complex which is an important component for cellular trafficking towards lysosomes. Cell biology became her automatic choice in pursuit of doctoral study. She is currently affiliated to Albert Pol’s lab as a PhD scholar at IDIBAPS where she is working on High-throughput screening of endosomes in different metabolic/genetic backgrounds. In her free time, she likes to read novels.

Helmholtz Institute, Munich, DE

Joël Tissink

Joël was drawn to the interesting field of metabolism and energy homeostasis during his biomedical studies in Groningen. He participated in research regarding diabetes and non-alcoholic fatty liver disease (NAFLD), and he got in touch with endo-lysosomal regulation and the impact on metabolic diseases. He is happy to continue in this field by investigating possible candidates and mechanisms herein. Other than science, he likes to do outdoor sports, listen to and play music, and watch movies and series. Here in Zurich and Munich, he would like to explore the mountains by bike or by hike, which are new to him as a Dutchman. 

University of Utrecht, NL

Orsolya Farkas

Orsolya obtained a bachelor’s degree in Laboratory Sciences from the University of Medicine and Pharmacy in Cluj-Napoca, Romania. She continued her studies by pursuing a research-oriented degree in Molecular Life Sciences at the Friedrich Schiller University in Jena, Germany. Here, she worked on establishing a liver-on-chip system mimicking a systemic infection caused by a fungal pathogen. Following this, she joined a life-science company in Cambridge UK, where she worked in the functional genomic team using the CRISPR-Cas9 tool for screening. She has always been interested in disease-oriented research and she thinks that the study of endo-lysosomal system in the context of metabolic diseases and therapy is an interesting and relevant topic.  

University Medical Center Groningen, NL

Ankia Visser

Ankia was born and raised in Cape Town, South Africa. She completed her bachelor’s degree at the University of Stellenbosch, South Africa. She decided to pursue a Master’s in biochemistry at the same university, where she studied the role of stress and inflammation in the development of hepatic insulin resistance. She is very excited to be a part of the EndoConnect team where she will be able to build on what she has learnt about metabolic syndrome in her MSc. She will be investigating novel lipid genes and their role in lipid metabolism at the UMCG in Groningen.  

University Medical Center Hamburg-Eppendorf, DE

Kim Hurkmans

Kim is a PhD student at the lab of Jörg Heeren in Hamburg. She is very broadly interested, that’s why she first studied Psychobiology (Neuroscience) at the University of Amsterdam. After that, she did the master Biomedical Sciences at the University of Groningen where she took an interest in epigenetics, the gut microbiome and the liver and now her research will focus on brown adipose tissue. 

University Medical Center Hamburg-Eppendorf, DE

David McGrath

David comes from Ireland where he did his bachelor’s at the University of Limerick, after which he studied MSc in Biomedical Sciences at Maastricht University, The Netherlands. He has experience in skeletal myocyte mitophagy and respiration, and myocardial energetics and cardiac function in humans. His EndoConnect project is in the labs of Prof. Sáez and Prof. Heeren at the UKE in Germany. His interests are endo-lysosomal communication, cardiometabolic disorders, adipocyte biology, advanced microscopy, and microfluidics, which he will use to investigate the role of endo-lysosomal membrane proteins in energy metabolism of brown and white adipocytes during cold-induced thermogenesis and metaflammation. 

UMCU, Utrecht, NL

Alejandra Puentes

Alejandra is a biologist graduated from the Pontificia Universidad Javeriana in Bogotá, Colombia. She did her research at the Instituto de Errores Innatos del Metabolismo where she worked with lentiviral vectors carrying the GALNS cDNA as a gene therapy approach for Mucopolysaccharidosis IVA, a lysosomal storage disease. In October 2021, she joined InteRNA and the Cell Biology, Metabolism & Cancer Division at Utrecht University in the Netherlands as a PhD student. She is working on elucidating the endo-lysosomal trafficking of lipid nanoparticles carrying miRNA mimics for cancer therapy.  

University of Helsinki, FI

Haoran Li

Haoran comes from China where he received his bachelor’s degree from Sichuan University, majoring in clinical medicine. He did a master’s at Fudan University, China, acquiring three years of full-time lab experience by investigating the relationship between bone and cholesterol metabolism. With a background in clinical and experimental biomedicine, he developed an interest in better understanding the mechanisms of lipid transport and lipid metabolic diseases. His EndoConnect project is under the guidance of Prof. Elina Ikonen at the University of Helsinki, Finland, where he investigates the mechanisms of endo-lysosomal lipid metabolism, trafficking and communication with other subcellular organelles.

University Medical Center Groningen, NL

Markus Barbosa

Markus obtained a BSc in Biology & Biochemistry from Knox College in the U.S. and a MSc in Biomedical Research from Universitat Pompeu Fabra in Barcelona, Spain. For his Masters project, he joined IDIBAPS Biomedical Research Institute where he studied the relationship between molecular regulation of lipid metabolism and colorectal tumorigenesis. This project sparked his interest in lipid metabolism and the role it plays in the development of pathologies. Markus is looking forward to starting his PhD at UMCG under Dr. Bart van de Sluis & Dr. Kuivenhoven with the aim of further elucidating on metabolic diseases.

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