Ph.D., Stanford University
Assistant Professor of Biology
A fundamental question in cell biology is how cells communicate with their environment, including both neighboring cells and the extracellular matrix. We use both biochemical and cell-based assays to investigate the molecular mechanisms underlying Notch signaling, which is involved in both normal development and human disease. The Notch receptor is a cell surface protein that requires direct cell-cell contact to be activated by a family of conserved membrane-tethered ligands expressed on neighboring cells. However, there is growing evidence that atypical proteins outside of this family can also activate Notch signaling.
We are currently investigating the function of one of the atypical ligands, microfibril-associated glycoprotein-2 (MAGP-2), which can interact with Notch and activate Notch signaling. In cell culture experiments we are dissecting the role of MAGP-2-Notch signaling using both loss-of-function (siRNA) and gain-of-function (overexpression) studies. Additionally, since it is not known which cells express MAGP-2 in vivo, we are localizing MAGP-2 RNA transcripts via in situ hybridization (ISH) in the developing mouse. These studies will reveal cell types that can potentially respond to MAGP-2-activated Notch signaling.
Nichols, J.T., Miyamoto, A., Olsen, S.L., D’Souza, B., Yao, C., Weinmaster, G. (2007) DSL-ligand endocytosis physically dissociates Notch1 heterodimers prior to activating proteolysis. J. Cell Biol. 176:445-458.
Miyamoto, A., Lau, R., Hein, P.W., Shipley, J.M., Weinmaster, G. (2006) Microfibrillar proteins MAGP-1 and MAGP-2 induce Notch1 extracellular domain dissociation and receptor activation. J. Biol. Chem, 281:10089-97.
Nehring, L.C., Miyamoto, A., Hein, P.W., Weinmaster, G. and Shipley, J.M, (2005) The Extracellular Matrix Protein MAGP-2 Interacts with Jagged1 and Induces its Shedding From the Cell Surface, J. Biol. Chem. 280(21):20349-55.