Dr Neil Morgan, Reader in Cardiovascular Genetics, at the Institute of Cardiovascular Science (ICVS), has been awarded a Multiple Principle Investigators (Multi PI) R01 Programme Grant from the National Institutes of Health (USA) to research the role of the SLFN14 gene in megakaryopoiesis and platelet development.
This prestigious $2.2 million four-year grant has been awarded jointly with Dr Andrey Pisarev, PhD at the SUNY Downstate Health Sciences University, his New York collaborator. The overarching goal of Multi PI awards is to maximise the potential of team science efforts in order to be responsive to the challenges and opportunities of the 21st century.
Drs Morgan and Pisarev plan to better understand platelets and their parent cells, the megakaryocytes, and from this obtain clues how production and function go wrong. With this knowledge, they will then identify new targets for drug development in this novel pathway which could prevent excessive bleeding in patients. On the other hand, drugs that mimic these pathways could be useful in preventing blood clot formation and reduce the chance of severe illnesses such as heart attacks and strokes.
“The overall goal of this programme is to investigate how mutations in SLFN14 cause fewer platelets to be produced, and for those that are produced, what causes the impaired ability of platelets to prevent blood loss,” Dr Morgan explained.
Considering that SLFN14 is a key regulator of megakaryopoiesis and of structural development of platelets, they plan to use an integral approach to investigate the role of SLFN14 in platelet biogenesis. They will employ novel SLFN14 models and inducible Pluripotent Stem Cell (iPSC) derived megakaryocytes (MKs) expressing SLFN14 patient mutations, in conjunction with biochemical, molecular biology, cellular biology techniques, and structural analysis via cryo-electron microscopy (cryo-EM).