Research

Research in the department of Anatomy and Embryology primarily concerns cardiovascular development and disease, historically an area of interest but with more recent focus on underlying molecular mechanisms that control normal and abnormal development in humans.

The heart is the first organ to form during embryonic development and its proper connection to the vasculature and blood circulation are controlled by a complex interplay of multiple signalling pathways. Maladaptation of these pathways not only leads to congenital heart and vascular defects but also to late onset cardiovascular disease. Conversely, recapitulating normal use can support directed differentiation of stem cells so that human derivatives of the cardiovascular lineages can be produced for a multiplicity of biomedical applications ranging from disease modelling and drug discovery to regenerative medicine. This research programme aims to define molecular and biomechanical mechanisms 1. used by progenitors to form cellular components of the heart and vasculature, 2. that support cardiovascular cell maturation to fully functional phenotypes and 3. that cause deregulation in cardiac and vascular disease. We use (pluripotent) stem cells, embryos and foetuses of chicken, mouse and human origin to identify functional signalling pathways in combination with a range of classical (embryo culture, histology, gross morphology, electrophysiology) and modern molecular techniques (molecular imaging, functional genomics, proteomics and epigenomics, high content analysis, development of genetic disease models) for this purpose.

The department is part of the LUMC profile area “Vascular and Regenerative Medicine” 

Collaboration with clinical departments is used as continuing a basis for deriving pluripotent stem cells bearing (cardiovascular and neural) disease genes for pathophysiology analysis in combination with drug discovery. A human fetal database and tissue bank has been established as a research resource for the community. A joint appointment in the department of Cardiology provides a clinical link to research on the developmental origin of congenital heart defects and long-term outcomes of childhood surgery. Development and pathomorphology of bicuspid aortic valves, cardiac conduction and innervation is explored in both genetic animal models and human tissues.

A new “organ on chip” research programme developing human tissue and disease modelling technology (hDMT) in microfluidic and biomechanical/electrical devices was initiated in 2015 as a collaboration between the three technical universities, several other universities and university medical centres, the Hubrecht Institute and pharma/biotech (Galapagos, GenMab). Synthetic human tissues derived from stem cells are incorporated in devices to provide complex models for drug discovery and safety pharmacology. In the first instance cardiac and vascular diseases and cancer were modelled on chip formats with neural (in collaboration with Erasmus MC) and skin (in collaboration with the AMC) following in 2016.

Research in the department is organized in two main themes 

  1. (Ab)normal cardiovascular development and disease. The primary goal is to obtain new insights into heart disease and heart development with view to developing new treatment strategies that range from (repurposing) drugs and risk profiling to surgical intervention. 
  2. Differentiation and Organ development. This embraces the primary competencies of the department and includes in depth knowledge of human embryo development through morphological, pathological, genetic and epigenetic analysis of an extensive collection of human fetal tissue. This forms the Centre for Human Development with links to a human fetal database (“Keygenes”) in which links between different organs at different developmental stages can be examined. 

These themes are lead by three senior (C.L. Mummery, S.M. Chuva de Sousa Lopes, M. de Ruiter) and four junior (M. Bellin, R.P. Davis, V.V. Orlova, M.R.M. Jongbloed) Principle Investigators; senior PI R. Passier is also Professor of Applied Stem Cell Biology at the University of Twente in 2015 and C.L. Mummery also holds a part-time chair of Vascular Microfluidics at the same university, part of a strategic collaboration between the LUMC and UT. Human (patient-derived) induced pluripotent stem cells used in multiple research lines are produced by the LUMC iPSC core facility.