Silvere Maria van der Maarel - BiographyCurriculum Vitae#

Silvere Maria van der Maarel is active in the rare disease field and is worldwide renowned for his critical contribution to our current understanding of the genetic and epigenetic underpinnings of facioscapulohumeral muscular dystrophy (FSHD). He did his PhD training in Human Genetics (Nijmegen, the Netherlands) where he was involved in the cloning of the POU3F4 gene underlying non-syndromic deafness and ZMYM3 as candidate gene for X-linked intellectual disability. After a brief postdoctoral training at the Max Planck Institute for Molecular Biology (Berlin, Germany) where he investigated disease-associated chromosomal breakpoints, the candidate joined the department of Human Genetics at the LUMC. He is currently the head of the department and his research interests are in chromatin diseases. His research mainly focuses on the pathogenesis of FSHD, a chromatin disease in which he made seminal contributions to the current understanding of the disease mechanism. His team laid the basis for the current FSHD disease model by showing that a D4Z4 repeat contraction in FSHD1, and mutations in SMCHD1, DNMT3B or LRIF1 in FSHD2, converge in a failure to repress DUX4 in skeletal muscle.

In addition to his interest in FSHD, Silvere Maria van der Maarel also studies another chromatin disease which particularly affects the chromatin structure of repetitive DNA: the primary immunodeficiency ICF syndrome. Here, he identified three of the four currently known disease genes. As for FSHD, his functional follow-up studies focus on the concept of mechanistic convergence in genetically distinct but clinically overlapping disease entities.

Finally, having a strong interest in muscle diseases, Silvere Maria van der Maarel also studies the acquired autoimmune disease MuSK-Myasthenia Gravis (MuSK-MG). He discovered that in contrast to common autoimmune diseases in which IgG1-3 autoantibodies elicit cytotoxicity, in MuSK-MG IgG4 autoimmune antibodies against MuSK create a physical barrier that disrupts normal neuromuscular junction homeostasis thereby defining a novel mechanism of autoimmunity.