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Scripps Research Joint Appointments

Faculty, Kellogg School of Science and Technology

Research Focus

Our laboratory is studying nucleocytoplasmic transport and the role of the nuclear envelope in the regulation of cell signaling, chromosome organization and differentiation. Nucleocytoplasmic transport is mediated by nuclear pore complexes (NPCs), large supramolecular assemblies that span the nuclear envelope. Transport of proteins and RNAs through the NPC is dependent on specific transport signals on the cargoes, the small GTPase Ran, and nuclear transport receptors called karyopherins, which carry protein and nucleic acid cargoes through the NPC by interaction with a series of nucleoporins. We are implementing a chemical biology approach, involving identification and analysis of small molecule inhibitors of nuclear import, to provide the basis for understanding the nuclear protein import pathway at a molecular level. Our studies also involve an analysis of the nuclear import of adenovirus DNA, and the nuclear export of HIV-1 mRNA. To study the nuclear envelope in cell signaling and differentiation, we are focusing on the nuclear lamina, a protein meshwork that lines the inner nuclear membrane. The lamina provides a structural framework for the nucleus, and helps to regulate epigenetic states of cells through effects on signaling and chromatin structure. We are analyzing a group of lamina-associated transmembrane proteins that we identified in a proteomics screen, for their roles in differentiation of striated muscle, adipocytes and other cells.

Education

Ph.D., Rockefeller University, 1979

Awards & Professional Activities

Editorial Boards: Journal of Cell Biology, BMC Cell Biology
NIH Study Section Member: Nuclear and Cytoplasmic Structure/Function and Dynamics

Selected References

For a complete list of publications: http://www.scripps.edu/gerace/publications_2000s.html

Naji, S., Ambrus, G., Cimermančič, P., Reyes, J.R., Johnson, J.R., Filbrandt, R., Huber, M.D. Vesely, P., Krogan, N.J., Yates III, J.R., Saphire, A.C. and Gerace, L.  (2012) Host cell interactome of HIV-1 Rev includes RNA helicases involved in multiple facets of virus production. Mol. Cell Proteomics. 4:M111.015313

Hintersteiner, M., Ambrus-Aikelin, G., Bednenko, J., Schmied, M., Gstach, H., Seifert, J., Singer E., Gerace, L. and Auer, M. (2010). Identification of a small molecule inhibitor of importin beta mediated nuclear import by confocal on-bead screening of tagged one-bead one-compound libraries. ACS Chem. Biol. 5:967-79.

Huber, M., Guan, T. and Gerace, L. (2009) Overlapping functions of nuclear membrane proteins NET25 (Lem2) and emerin in regulation of ERK signaling in myoblast differentiation. Mol. Cell Biol. 29:5718-5728. 

Liu, G.H., Guan T., Datta K., Coppinger J., Yates J.,III. and Gerace, L. (2009) Regulation of myoblast differentiation by the nuclear envelope protein NET39. Mol. Cell Biol. 29:5800-5812.

Wodrich H., Cassany A., D’Angelo M.A., Guan T., Nemerow G. and Gerace L. (2006) Adenovirus core protein pVII is translocated  into the nucleus by multiple import receptor  pathways. J. Virology. 80:9608-9618.

Ohba, T., Schirmer, E.C., Nishimoto, T. and Gerace, L. (2004) Energy and temperature dependent transport of integral proteins to the inner nuclear membrane via the nuclear pore. J. Cell Biol. 167:1051-1062.

Schirmer, E., Florens, L., Guan, T., Yates, J.R. and Gerace, L. (2003) Nuclear membrane proteins with potential disease links found by subtractive proteomics. Science. 301:1380-1382.

Cingolani, G., Bednenko, J., Gillespie, M.T. and Gerace, L.  (2002) Molecular basis for the recognition of a nonclassical nuclear localization signal by importin beta. Mol. Cell. 10:1345-1353.

Kehlenbach, R.H., Dickmanns, A., Kehlenbach, A., Guan, T. and Gerace, L. (1999) A role for RanBP1  in the release of CRM1 from the nuclear pore complex in a terminal step of nuclear export. J. Cell Biol. 145:645-657.

Mahajan, R., Gerace, L. and Melchior, F. (1998) Molecular characterization of the SUMO-1 modification of RanGAP1 and its role in nuclear envelope association. J. Cell Biol. 140:259-270.

Melchior, F., Paschal, B., Evans, J. and Gerace, L. (1993) Inhibition of nuclear protein import by nonhydrolyzable analogues of GTP and identification of the small GTPase Ran/TC4 as an essential transport factor.  J. Cell Biol. 123:1649-1660.

Foisner, R. and Gerace, L. (1993)  Integral membrane proteins of the nuclear envelope interact with lamins and chromosomes and binding is modulated by mitotic phosphorylation.  Cell. 73:1267-1279.