Vascular stability – the capacity of mature endothelium to maintain barrier integrity, resist aberrant sprouting, and support proper perfusion – is essential for tissue homeostasis. Loss of vascular stability is a defining feature of several debilitating and/or lethal conditions which are linked to and worsen with age. The Ruohola-Baker laboratory has recently shown that novokines – agonists built from two minibinders which force unrelated receptors into proximity – can hijack endogenous receptor machinery to drive novel signaling. With funding as an ISCRM Fellow, Audrey will design minibinders against vascular-relevant receptors and convert them into novokines. These novel signaling modalities will be screened for their effects on endothelial barrier permeability using a transwell barrier assay, alongside further characterization of their effects on endothelial differentiation. Successful novokines will enable advances in differentiated endothelial maturity and stability beyond what native growth factors can achieve alone.
