Our 2nd 2021 Research Recipient

We are pleased to announce the second recipient of our 2021 Research Grant. 

Dr. Robert Semple will receive a $25,000 grant for the project titled “Human Pluripotent Stem Cells as a Model to Interrogate Pathogenesis and Developmental Origins of CLOVES”

This project will investigate human induced pluripotent stem cells (iPSCs) as a model system to examine the developmental origins of CLOVES, and to test new approaches to treatment.  iPSCs are made by “reprogramming” cells from biopsies of healthy adult volunteers.  They have the characteristics of true human embryonic cells, including the ability to turn into almost any cell type in the human body under the right conditions.  This means that these cells can be used in the lab to examine abnormal development and growth of all the tissues affected in CLOVES syndrome.  Crucially, only human cells are involved, which is important as mouse models do not perfectly mimic CLOVES when human mutations are introduced.  For this project, genetic “scissors” have already been used to introduce one or two CLOVES syndrome PIK3CA mutations to iPSCs.  The effect of these mutations on the ability of cells to make blood vessel and blood cells will first be examined, and then CLOVES will be mimicked by mixing different proportions of unaffected and CLOVES syndrome mutant cells.  Analysis will use advanced single cell sequencing techniques to assess the points in development where abnormalities occur, to assess whether the presence of cells with mutations affects the growth of healthy cells, and to assess the effects of drugs on the abnormalities observed.  The project will be a collaboration among scientists with expertise in CLOVES, in blood and blood vessel development, and in advanced statistical analysis of single cell sequencing studies.

Dr. Robert Semple
University of Edinburgh Centre for Cardiovascular Science
47 Little France Crescent
Edinburgh, EH16 4TJ, UK