San Rocco Therapeutics
Product Pipeline > CD47
CD47
CD47 (Cluster of Differentiation 47) is a transmembrane protein found widely on human cells that functions as a receptor for the secreted protein thrombospondin-1 (TSP1) and for cell membrane signal regulatory protein α (SIRPα). TSP1 binds with high affinity to CD47 (~kD 12 pM) whereas CD47 binds SIRPα with much lower affinity. The TSP1-CD47 axis regulates redox signaling by limiting the beneficial effects of the biogas nitric oxide and by stimulating NADPH oxidase-derived superoxide production. This has multiple negative effects upon angiogenesis, wound healing, blood flow, and cardiovascular function. Thus, the TSP1-C47 interaction promotes hypoxia, ischemia, cardiac failure and transplant injury.
TSP1, via CD47, also limits key self-renewal transcription factors including Oxt3/4, Sox2, Klf4 and cMyc. This leads to suppression of cell growth and stemness. Conversely, removing the TSP1-CD47 signal allows for cells to revert to a pluripotent phenotype. Thus, the TSP1-CD47 axis represents a natural brake upon the so-called Yamanaka factors.
In the immune system, both the TSP1-CD47 axis and the CD47-SIRPα axis serve as restraints (checkpoints) upon cell activation. While TSP1-CD47 restrains T, natural killer and dendritic cells, CD47-SIRPα primarily suppresses phagocytosis. The actions of these pathways on immune cells have implications for auto-immunity and are being leveraged as cancer therapies. Beyond this, the TSP1-CD47 axis is unique as it is an independent regulator of cell responses to the genotoxic stress of radiation and chemotherapy. Lowering the TSP1-CD47 signal provides protection to normal cells and tissues from high-dose radiation and chemotherapy while rendering cancers more sensitive to the genotoxic stress.
San Rocco Therapeutics is working with Dr. Jeff Isenberg to develop new therapies that alter CD47 signaling.
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