Isabella Graef

Postdoctoral Advisees

• Ah Ryon Cho, Suhua Deng, Alexandra Esteras Chopo, Lining Liu, Yitai Tang

Graduate & Fellowship Program Affiliations

• Cancer Biology
• Neurosciences

Web Site Links

• Graef Lab Homepage

Research Interests

We are interested in addressing questions in neuronal development and function by a combination of genetic, cell biological, biochemical and chemical approaches.
The main focus of our lab is centered around two topics: 1) the interface of signaling and gene regulation in neuronal development, with a focus on calcineurin-NFAT signaling; 2) the development of small molecules, which interfere with pathogenic protein-protein interactions underlying neurodegenerative diseases.

Publications

• An essential switch in subunit composition of a chromatin remodeling complex during neural development. Lessard J,  Wu JI, Ranish JA, Wan M, Winslow MM, Staahl BT, Wu H, Aebersold R, Graef IA, Crabtree GR.  Neuron.  2007; 55 (2): 201-15
• NFAT signaling and the invention of vertebrates. Wu H,  Peisley A, Graef IA, Crabtree GR.  Trends Cell Biol.  2007; 17 (6): 251-60
• NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21 Arron*, Winslow*, Polleri*, (*equally contributing, #corresponding authors),  Chang, Wu, Gao, Neilson, Chen, Heit, Kim, Yamasaki, Miyakawa, Francke, Graef*#, Crabtree#.  Nature.  2006; 441 (June 1): 595-600
• Harnessing chaperones to generate small-molecule inhibitors of amyloid beta aggregation. Gestwicki JE,  Crabtree GR, Graef IA.  Science.  2004; 306 (5697): 865-9
• Neurotrophins and netrins require calcineurin/NFAT signaling to stimulate outgrowth of embryonic axons. Graef IA,  Wang F, Charron F, Chen L, Neilson J, Tessier-Lavigne M, Crabtree GR.  Cell.  2003; 113 (5): 657-70
• Signals transduced by Ca(2+)/calcineurin and NFATc3/c4 pattern the developing vasculature. Graef IA,  Chen F, Chen L, Kuo A, Crabtree GR.  Cell.  2001; 105 (7): 863-75
• Regulation of dendritic development by neuron-specific chromatin remodeling complexes. Wu JI,  Lessard J, Olave IA, Qiu Z, Ghosh A, Graef IA, Crabtree GR.  Neuron.  2007; 56 (1): 94-108
• Unc-51-like kinase 1/2-mediated endocytic processes regulate filopodia extension and branching of sensory axons. Zhou X,  Babu JR, da Silva S, Shu Q, Graef IA, Oliver T, Tomoda T, Tani T, Wooten MW, Wang F.  Proc Natl Acad Sci U S A.  2007; 104 (14): 5842-7
• Role of transcription factor NFAT in glucose and insulin homeostasis. Yang TT,  Suk HY, Yang X, Olabisi O, Yu RY, Durand J, Jelicks LA, Kim JY, Scherer PE, Wang Y, Feng Y, Rossetti L, Graef IA, Crabtree GR, Chow CW.  Mol Cell Biol.  2006; 26 (20): 7372-87
• 'Nature-inspired' drug-protein complexes as inhibitors of Abeta aggregation. Bose M,  Gestwicki JE, Devasthali V, Crabtree GR, Graef IA.  Biochem Soc Trans.  2005; 33 (Pt 4): 543-7
• Recruitment of the extracellular signal-regulated kinase/ribosomal S6 kinase signaling pathway to the NFATc4 transcription activation complex. Yang TT,  Xiong Q, Graef IA, Crabtree GR, Chow CW.  Mol Cell Biol.  2005; 25 (3): 907-20
• A field of myocardial-endocardial NFAT signaling underlies heart valve morphogenesis. Chang CP,  Neilson JR, Bayle JH, Gestwicki JE, Kuo A, Stankunas K, Graef IA, Crabtree GR.  Cell.  2004; 118 (5): 649-63
• Jun N-terminal kinase 2 modulates thymocyte apoptosis and T cell activation through c-Jun and nuclear factor of activated T cell (NF-AT). Behrens A,  Sabapathy K, Graef I, Cleary M, Crabtree GR, Wagner EF.  Proc Natl Acad Sci U S A.  2001; 98 (4): 1769-74
• Evolutionary relationships among Rel domains indicate functional diversification by recombination. Graef IA,  Gastier JM, Francke U, Crabtree GR.  Proc Natl Acad Sci U S A.  2001; 98 (10): 5740-5
• c-Jun NH2-terminal kinase (JNK)1 and JNK2 have similar and stage-dependent roles in regulating T cell apoptosis and proliferation. Sabapathy K,  Kallunki T, David JP, Graef I, Karin M, Wagner EF.  J Exp Med.  2001; 193 (3): 317-28
• NFAT signaling in vertebrate development. Graef IA,  Chen F, Crabtree GR.  Curr Opin Genet Dev.  2001; 11 (5): 505-12
• L-type calcium channels and GSK-3 regulate the activity of NF-ATc4 in hippocampal neurons. Graef IA,  Mermelstein PG, Stankunas K, Neilson JR, Deisseroth K, Tsien RW, Crabtree GR.  Nature.  1999; 401 (6754): 703-8
• Signaling through calcium, calcineurin, and NF-AT in lymphocyte activation and development. Stankunas K,  Graef IA, Neilson JR, Park SH, Crabtree GR.  Cold Spring Harb Symp Quant Biol.  1999; 64 505-16
• Defects in actin-cap formation in Vav-deficient mice implicate an actin requirement for lymphocyte signal transduction. Holsinger LJ,  Graef IA, Swat W, Chi T, Bautista DM, Davidson L, Lewis RS, Alt FW, Crabtree GR.  Curr Biol.  1998; 8 (10): 563-72
• Proximity and orientation underlie signaling by the non-receptor tyrosine kinase ZAP70. Graef IA,  Holsinger LJ, Diver S, Schreiber SL, Crabtree GR.  EMBO J.  1997; 16 (18): 5618-28
• The transcriptional paradox: octamer factors and B and T cells. Graef IA,  Crabtree GR.  Science.  1997; 277 (5323): 193-4
• The mechanism of action of cyclosporin A and FK506. Ho S,  Clipstone N, Timmermann L, Northrop J, Graef I, Fiorentino D, Nourse J, Crabtree GR.  Clin Immunol Immunopathol.  1996; 80 (3 Pt 2): S40-5
• A general strategy for producing conditional alleles of Src-like tyrosine kinases. Spencer DM,  Graef I, Austin DJ, Schreiber SL, Crabtree GR.  Proc Natl Acad Sci U S A.  1995; 92 (21): 9805-9