DMM Outstanding Paper Prize 2020 winner: Sarah Colijn

By the time Sarah Colijn was twelve years old, she had already lived with her family in five different states. At age twelve, Sarah and her family finally settled down in Norman, Oklahoma – the land of Sooner football and tornadoes. Sarah was always greatly attracted to the idea of a career in a STEM field, but it wasn't until she read an article about malaria in an edition of National Geographic that she fell in love with the idea of biomedical research.

Sarah attended the University of Oklahoma with a National Merit Scholarship. In 2013, she received her bachelor's degree in Biochemistry with a minor in Physics. She then started graduate school at the University of Oklahoma Health Sciences Center and joined the lab of Dr Courtney Griffin at the Oklahoma Medical Research Foundation, where she discovered that her scientific passion is studying the blood vasculature.

Sarah's first project involved exploring the role of chromatin-remodeling complexes in vascular development and vessel stability. By using genetically-modified mouse embryos as her animal model, Sarah found that the executioner protein RIPK3 – from the cell death pathway known as necroptosis – is carefully regulated by chromatin-remodelling complexes at mid-gestation to prevent vascular haemorrhage. Furthermore, she and her colleagues discovered that endothelial RIPK3 levels are particularly sensitive to hypoxia, i.e. physiologically low levels of blood oxygen, as observed during gestation. This bolstered the finding that endothelial RIPK3 levels must be suppressed at mid-gestation to support embryonic survival and vascular integrity (Colijn et al., 2020a).

Sarah's second project was to investigate the detrimental role of RIPK3 in a murine model of atherosclerosis. Necroptosis – and, thus, by association RIPK3 – is considered to be harmful because it can exacerbate inflammation and, theoretically, make atherosclerosis worse. It has been proposed that necroptosis and RIPK3 are viable targets for drugs that prevent atherosclerosis as macrophages are able to undergo necroptosis within atherosclerotic plaques. However, to Sarah's great surprise, she found that inhibition of RIPK3 in certain cell types has unexpected and pro-atherogenic effects, indicating that it is a poor target for drug design. In particular, deletion of RIPK3 in either macrophages or endothelial cells revealed that RIPK3 has an athero-protective role in these cell types (Colijn et al., 2020b). Sarah's work challenges research regarding atherosclerosis and necroptosis to rethink the role of RIPK3 and to acknowledge that it can function in a non-pathological way; she and her colleagues suspect that RIPK3 functions in a multitude of pathways that have very little to do with necroptosis. In fact, this is becoming more and more clear as Dr Griffin's group continues to study RIPK3 in the vasculature during embryogenesis and postnatally. Sarah is honoured that her work with RIPK3 and atherosclerosis was chosen as the winner of the 2020 DMM Prize as the most outstanding contribution to the journal.

After receiving her Ph.D. in 2019, Sarah began her postdoctoral position at Washington University in St. Louis with Dr Amber Stratman. She has shifted animal models and now works with zebrafish to uncover blood-flow-dependent mechanisms that regulate vascular development. Sarah hopes to carry on the legacy of outstanding female mentorship she has received from Drs Griffin and Stratman as she continues in her own academic career.