Martha Cyert

By studying calcineurin, the conserved Ca2+/calmodulin-regulated protein phosphatase, we aim to discover and elucidate new Ca2+-regulated signaling pathways in humans. The calcineurin phosphatase dephosphorylates proteins only when Ca2+ signaling is triggered, for example by a hormone, growth factor, neurotransmitter etc. Previous work from the Cyert lab discovered how calcineurin allows yeast cells to survive environmental stress (Goldman et al, 2014, Molecular Cell). Currently, we are studying human calcineurin which is ubiquitously expressed and plays critical roles throughout the body, but especially in the nervous, cardiac and immune systems. Calcineurin is best known for activating the adaptive immune response by dephosphorylating the NFAT transcription factors, and is the target of widely prescribed immunosuppressant drugs, FK506 (tacrolimus) and Cyclosporin A. However, these drugs cause many adverse effects due to inhibition of calcineurin in non-immune tissues, where the majority of calcineurin substrates and functions remain to be discovered. We are using a variety of experimental and computational strategies to systematically map human calcineurin signaling pathways in healthy and diseased cells. We have uncovered surprising roles for calcineurin in Notch signaling, regulation of transport though nuclear pores, and at centrosomes. See our recent paper (Wigington, Roy et al, 2020, Molecular Cell) to learn more about our studies.