Education, Honors and Awards

Research Interests

Our current research focuses in the molecular architecture and biochemical functions of protein domains involved in signal transduction, membrane trafficking and cancer progression. We aim to understand how protein domains, i.e. membrane-associated protein domains, specifically interact with downstream effectors and elicit signaling pathways. Our research program employs a multidisciplinary approach to investigate these problems, including high field NMR spectroscopy, circular dichroism, protein computer modeling, liposome binding assays, fluorescence spectroscopy and surface plasmon resonance spectroscopy among others. These techniques will help to elucidate the mechanism of bilayer insertion of protein modules in sufficient structural and functional detail to build up the quantitative basis for predicting subcellular targeting. We work at the interface of structural and cellular biology as well. Most of our research is carried out in collaboration with other research groups that center on cellular biological features. This allows us to look at cell-based signaling and to correlate our in vitro studies in real biological systems. Briefly, some of the current projects are:

Canonical Wnt signaling pathway: We focus on establishing the roles of Wnt-related protein domains at the structural and functional level to understand the mechanism of regulation of Wnt proteins that create the divergences and equilibrium between the different branches of this signaling pathway.

Rho GTPases: We are interested to answer one of the intriguing questions in this field: why are Rho GTPases recruited to the plasma membrane over other internal membranes in the cell? Using the approaches described above, we are currently investigating this exciting area by looking at possible ligands that regulate this process.

Selected Publications

1. Capelluto D.G.S., Hellman U, Cazzulo J.J. and Cannata J.J.B.. Serine hydroxymethyltransferase of Trypanosoma cruzi: Purification and some properties. Eur. J. Biochem., 267, 1-9 (2000).
2. Capelluto D.G.S., Kutateladze T.G., Habas R., Finkielstein C.V., He X. and Overduin M. The DIX domain targets Dishevelled to actin stress fibers and vesicular membranes. Nature, 419, 726-729 (2002).
3. Kutateladze T.G., Capelluto D.G.S., Ferguson C.G, Cheever M., Kutateladze, A, Prestwich G.D. and Overduin M. Multivalent mechanism of membrane insertion by the FYVE domain. J. Biol Chem. 279, 3050-3057(2004).
4. Capelluto D.G.S. and Overduin M. Secondary structure, ¹H, ¹³C and ¹⁵N resonance assignments and molecular interactions of the Dishevelled DIX domain. J. Biochem Mol. Biol., 38, 243-247 (2005).
5. Tokonzaba E., Capelluto D.G.S., Kutateladze T. and Overduin M. Phosphoinositide, phosphopeptide and pyridone interactions of the Abl SH2 domain, Chem. Biol. Drug Des., 67:230-237 (2006).
6. Finkielstein C.V., Overduin M. and Capelluto D.G.S. Cell migration and signaling specificity is determined by Rac1's phosphatidylserine recognition motif. J. Biol. Chem., in press (2006).