Isabella A. Graef

Isabella initiated many new areas of research in our lab including work on the development of the nervous system and the development of the cardiovascular system. She demonstrated that the assembly and patterning of vessels in the mouse embryo requires calcineurin signaling through NFATc3/c4 (Cell 2001). Much of the role of NFAT signaling appears to be mediated by regulation of VEGF expression. She initiated studies of the role of calcineurin/NFAT in the nervous system, demonstrating that these proteins were regulated by L-type calcium channels in adult neurons (Nature 1999) and responded selectively to stimuli of different frequency. She found that axon outgrowth in the early embryo in response to netin and neurotrophins (and perhaps other guidance cues) requires calcineurin B1 and NFATc2/c3/c4. Her work demonstrated that these guidance clues us calcineurin and NFATc proteins to accelerate the rate of advance of the growth cone, allowing it to meet developmental time deadlines (Cell 2003). To do this work Isabella worked with Fan Wang from Mark Tessier-Lavigne’s lab. Fan is now on the faculty at Duke. Isabella had the original insight that the defects in the NFATc and calcineurin mutant mice reproduced essentially all of the characteristics of Down Syndrome, leading to the discovery that overexpression of two genes, DSCR1 and Dyrk1a, in the critical region of chromosome 21accounted for many of the characteristics of this disease (Nature 2006). She now has her own lab at Stanford University and can be reached at: