Clara van Karnebeek is a clinician-scientist in pediatrics and biochemical genetics, focused on the discovery of novel inborn errors of metabolism, their molecular and biochemical pathophysiology, and identification of treatment targets and implementation of these strategies in clinical trials for rare diseases.

She chairs collaborative research teams, including the International PDE Consortium comprising patients and families, clinicians and scientists. Clara has successfully applied new treatments (nutritional, small molecules, nucleic-acid-based , developed guidelines and digital tools to translate novel technologies and knowledge into the practice of P4-medicine (participatory, personalized, predictive, preventive) for better health outcomes. She is the founder and director of ‘United for Metabolic Diseases'.

Main Research Area; Gene Therapy, Viral and genetic engineering. In vivo studies in mouse models.

As a scientist and physician, my time (both clinical and research) is dedicated to developing new treatments for genetic brain disorders such as Frontotemporal dementia (FTD). I work on a number of other brain diseases including pyridoxine-dependent epilepsy, Fragile X Syndrome, amyotrophic lateral sclerosis, and Huntington‘s disease (HD). I am currently the founding Co-Editor-in-Chief of The Journal of Huntington’s Disease. My research group has extensive expertise in developing mouse models of human brain diseases, incluring YAC transgenic mouse model of HD, a mouse model of Juvenile ALS caused by mutations in the gene encoding for alsin. The development of the HD mouse model precipitated a series of important papers over the last several years that have shed new light onto the underlying pathogenic mechanisms of HD including: The first direct link between the HD gene mutation and increased neuronal susceptibility to excitotoxicity, identification of a direct mitochondrial defect caused by mutant huntingtin in HD, demonstration that caspase-6 mediated cleavage of huntingtin is a critical step in HD pathogenesis, and the first evidence for testicular degeneration in HD. My lab has recently developed mice with overexpression, constitutive deletion, and conditional deletion of the progranulin gene, a causative gene in Frontotemporal Dementia. We have established a mouse model of pyridoxinedependent epilepsy due to ATQ deletions that recapitulates the seizure, biochemical, and phenotypic characteristics of the human disease. I recently performed the first-in-human administration of huntingtin gene silencing for HD using an intrathecal antisense oligonucleotide.

Prof. Hrabĕ de Angelis’ areas of research include genetics, diabetes, phenotyping and data mining. He studied biology at Philipps University in Marburg and completed his PhD on the influence of growth factors on early embryonic development in 1994. During his time as a postdoctoral researcher (1994 – 1997) at the Jackson Laboratory in Bar Harbor (USA), he examined the Delta/Notch signaling pathway and somitogenesis in mouse models.

Since 2000, he has been director of the Institute of Experimental Genetics at the Helmholtz Zentrum München. In 2003, he was appointed to the Chair of Experimental Genetics at TUM. He is also the director of the European research consortium "INFRAFRONTIER" and coordinated 5 related EU research infrastructure projects. In 2001, he founded the German Mouse Clinic (GMC) for the systemic analysis of mouse models for human disease. Prof. Hrabĕ de Angelis is also co-founder and board member of the German Center for Diabetes Research.

Stefan Kölker is a clinician scientist in Pediatrics, focusing on Pediatric Metabolic Medicine and Pediatric Neurology at the Centre for Pediatrics and Adolescent Medicine at Heidelberg University Hospital. His major scientific interest is deep phenotyping, the elucidation of mechanistic pathways, and identification and evaluation of innovative therapies in neurometabolic and other rare disorders, and the development of preventive care strategies through newborn screening.
He leads a multi-professional team of clinician and medical scientists at Heidelberg University, chairs collaborative international research consortia, such as E-IMD, and with his team manages long-term observational studies using interoperable patient registries, such as U-IMD (the official registry of MetabERN). He has established and investigated various disease models for neurometabolic disorders, focuses also on biomarker research, and has developed guidelines.

Dirk LEFEBER, Ph.D., is Professor “Glycosylation disorders in Neurology” at the Radboud University Medical Center, Translational Metabolic Laboratory, Department of Neurology. He received his Master’s degree in chemistry at Utrecht University, awarded with the Unilever Research prize, followed by a PhD in chemical and analytical glycosciences at the same university (with prof. Kamerling and prof. Vliegenthart). He followed a post-doctoral training on polysaccharides in infectiology at the Eijkman-Winkler institute for infectious diseases (Utrecht, The Netherlands), after which he took a position as staff member Glycosylation Disorders at the Radboud UMC to establish an independent research group. This included a training to clinical biochemical geneticist. He has founded the Radboudumc Center of Expertise for genetic Disorders of Glycosylation, formally recognized by the Dutch government, and received several awards, including the SSIEM award (2010&2016) and the prestigious personal VIDI and VICI grants from the Netherlands Scientific Organisation. He has established the world-wide quality control scheme for CDG diagnostics within ERNDIM.

Research in the Lefeber lab is focused on the biological mechanisms of protein glycosylation in human disease and the translation of resulting insights to improve patient care. Using a combination of mass spectrometry (glycomics/glycoproteomics) and genomics, many gene defects could be elucidated. Current focus is on the tissue-specific mechanisms in sugar metabolism, which is studied by metabolic (flux) analysis in patient-derived organ on chip models of (heart and skeletal) muscle and brain.

Carole Linster is an established metabolic biochemist with biomedical background. Her prime research interest lies in the identification of new metabolic protein functions and the study of their implication in human disease. She has contributed pioneering work to the emerging concept of metabolite damage control, with the discovery of multiple metabolite repair enzymes and the finding that loss-of-function mutations in some of them result in deleterious disease. At LCSB she developed platforms for highthroughput yeast phenotypic screens and for MS-based metabolomics analyses.

Dr. Linster has accumulated experience working with model organisms, including E. coli, S. cerevisiae, C. elegans, zebrafish, and rat. Since joining the LCSB, she has intensively collaborated with the LCSB aquatic platform, developing an expertise in modelling inborn errors of metabolism in zebrafish.

Giancarlo la Marca is a clinical chemist expert in newborn screening for metabolic diseases, clinical chemistry and pediatric pharmacology. His team performs NBS for Tuscany and Umbria Regions in Italy. The NBS, Clinical Chemistry and Pharmacology Lab in Florence directed by him, is serving as a phase I/II central lab for several clinical trials aimed to discovery gene therapies for the treatment of metabolic disorders.

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