The lab of Dr Maarten Fornerod can be found in the Ee-building of the Erasmus MC (room nr. Ee10-65)
Tel: +31 10 7032978
PhD student: Alexandra Piët
Field(s) of expertise
Main biological questions
1) The role of lipid signaling in cell cycle progression, neuronal development and transcriptional regulation
2) The genomic landscape of pediatric acute leukemia
• Lipid signaling
Cortical microcephaly is a genetically diverse congenital disease, with substantial socioeconomical impact. We identified a homozychous splice site mutation in the sphingomyelinase D4 gene, leading to a >99% depletion of wt mRNA. Our findings are corroborated by two independent families with severe microcephaly and null or splice site mutations in the same gene. Fibroblasts dereived from patients show a mild cell cycle defect. Gene expression analysis suggest that SMPD4 mutation impacts a specific lipid signaling pathway, which acts on many different levels in the cell, including transcription complex regulation. We will evaluate this hypothesis using mass spectrometric lipid metabolomic analysis. We use single cell transcriptomics to elucidate cell cycle state specific differences in gene expression. Also, we use subcellular localization studies and chromatin IP to correlate changes in gene expression with changes in signaling lipid activity. These studies may open a novel perspective on the role of lipids and lipid signaling in cell biology and nuclear function.
• Genomic landscape of pediatric acute leukemia
Pediatric acute leukemia is a diverse genetic disorder of the blood in infants or children, also with substantial socioeconomical impact. We have previously studied a cohort of acute megakaryoblastic leukemias, which resulted in a improved stratification and direct recommendations for clinical practice, both in diagnosis and therapy. At present we are studying a cohort of pediatric acute myeloid leukemias (AMLs) of which there is no known genetic driver. The lack of such driver impedes progress in diagnosis and therapy for this group of patients, which accounts for ~20-30% of all pediatric AMLs. Using a combination of RNAseq, exome seq, whole genome seq, copy number and patient clinical data, we are identifying novel subgroups with specific characteristics. In particular we are interested in the occurance of dysregulation of the CTCF and cohesin complex in a subset of patient samples. This line of research may open a novel perspective on the role of cohesin and CTCF in leukemia, not limited to the myeloid lineage.