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Molecular Medicine

Faculty

Larry Gerace, Ph.D.

Professor
Department of Molecular Medicine
California Campus
Laboratory Website
lgerace@scripps.edu
(858) 784-8514

Scripps Research Joint Appointments

Faculty, Graduate Program

Research Focus

Functions of the nucleus and endoplasmic reticulum

Our laboratory is studying the functions of the cell nucleus, with focus on the properties of the nuclear envelope (NE) and associated nuclear lamina, and the process of mRNA biogenesis.  We also are analyzing the mechanisms by which the NE and endoplasmic reticulum membranes regulate transcription factors that control lipid biosynthesis. The NE dictates the functional properties of the nucleus via two distinctive associated components.   These are the nuclear pore complexes, protein channels spanning the NE that control trafficking of proteins and RNAs between the nucleus and the cytoplasm, and the nuclear lamina, a protein meshwork lining the NE that helps to specify chromatin structure and activity.  Our approaches to studying nuclear function include analysis of cultured cells by various biochemical and molecular approaches in combination with live cell fluorescence imaging, and the use of mouse genetic models to study the role of nuclear lamina components in tissue-specific functions linked to human disease.

The nuclear lamina, which consists of a polymer of nuclear lamins and associated membrane proteins, is recognized to be a nexus for integration of nuclear functions.  The lamina anchors chromosomes to the nuclear periphery, promotes gene silencing and regulates a host of signaling pathways.  Mutations in certain lamina proteins cause over 15 human diseases termed “laminopathies,” which include muscular dystrophies, lipodystrophies and premature aging.  How mutations in lamina proteins leads to laminopathies remains unclear.  Since many of these diseases affect striated muscle, we are using muscle as a model system to study the functions of relevant lamina components.  We currently are analyzing lamina proteins that modulate MAP kinases and IGF signaling, pathways that are central to many programs of gene expression in myoblasts.  We also are characterizing lamina proteins involved in specifying alternative differentiation fates of stem cells, and are analyzing how certain NE/ER proteins that bind cholesterol control the activity of sterol regulatory element binding proteins, master regulators of lipid biosynthesis.

Biogenesis of mRNA involves a highly interconnected set of processes beginning with transcription and culminating with productive export of mRNA to the cytoplasm through the nuclear pore complexes.  As a model system for mRNA biogenesis, we are studying the unspliced HIV-1 mRNA.  Many posttranscriptional properties of this mRNA are dictated by the viral transactivator protein Rev.   We have identified a set of DEAD-box RNA helicases that interact with Rev and that are required for various stages of HIV replication.  Since DEAD box helicases are involved in virtually all aspects of the mRNA life cycle including the remodeling of mRNA-protein complexes, we seek to understand how these proteins control the fate of HIV-1 unspliced mRNA in relation to its stability, trafficking, translation and assembly as the viral genome.

Education

Ph.D., Rockefeller University, 1979
B.A., Natural Sciences, Johns Hopkins University, 1973

Awards & Professional Activities

1982-85 Searle Scholars Award; 1984-89, NIH Research Career Development Award; 1987-1990 & 1992-present Monitoring Editor, Journal of Cell Biology; 1986 Outstanding Young Scientist of Maryland; 1987 RR Bensley Award; 1988-1990 Section Editor, Current Opinion in Cell Biology; 1990 Co-chair, Program Committee for Annual Meeting of American Society for Cell Biology; 1991 Nominations Committee, American Society for Cell Biology; 1994 Co-chair, Molecular Cell Biology Gordon Conference; 1997 Organizer, Keystone Symposium on Functional Organization of the Nucleus; 1998-2005 Editorial Board, Molecular Biology of the Cell; 2000-2003 Keystone Symposia Advisory Board; 2002-2003 Editorial Board, Journal of Biological Chemistry; 2004-2008 Editorial Board, BMC Cell Biology; 2008-present, Associate Editor, BMC Cell Biology; 2011-present, Editorial Board, Nucleus; 2013-present, Member, Nuclear and Cytoplasmic Structure/Function and Dynamics NIH Study Section.

Selected References

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

Huber, M.D., Vesely, P.W., Datta, K. and Gerace L. (2013) Erlins restrict SREBP activation in the ER and regulate cellular cholesterol homeostasis. J. Cell Biol. 11:427-36. 

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.

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.

Molecular Medicine Seminar Series

CA Faculty

Asahara, Hiroshi
Balch, William E.
Boddy, Michael
Buxbaum, Joel
Catz, Sergio
Conti, Bruno
Cravatt, Benjamin
D'Lima, Darryl
DerMardirossian, Celine
Deryugina, Elena
Elias, Darlene
Encalada, Sandra
Felding, Brunhilde
Fowler, Velia
Friedlander, Martin
Gerace, Larry
Gottesfeld, Joel
Griffin, John
Hanneken, Anne
Heeb, Mary Jo
Henderson, Scott
Hoch, James
Joazeiro, Claudio
Johnson, Eric
Kanaji, Taisuke
Kay, Steve
Kelly, Jeffery
Koziol, James
Lamia, Katja
Lazzerini Denchi, Eros
Lipton, Stuart
Loring, Jeanne F.
Loskutoff, David
Lotz, Martin
Makarenkova, Helen P.
Mc Millan, Robert
Miles, Lindsey
Milner, Richard
Modena, Brian
Mosnier, Laurent
Paulson, James C.
Perego, Marta
Petrascheck, Michael
Pollard, Kenneth Michael
Quigley, James P.
Reed, Steven
Roberts, Edward
Rosen, Hugh
Ruggeri, Zaverio
Russell, Paul
Saez, Enrique
Smider, Vaughn
Srinivasan, Supriya
Steinhubl, Steven
Sutcliffe, J.
Tan, Eng
Topol, Eric
Vanderklish, Peter
Vogt, Peter K.
Waalen, Jill
Wiseman, Luke
Wittenberg, Curt
Wolan, Dennis W.
Wu, Peng
Wu, Xiaohua
Yang, Xiang-Lei
Yates III, John


FL Faculty

Bohn, Laura M.
Cameron, Michael
Duckett, Derek
Gill, Matt
Griffin, Patrick
Hansen, Scott
Kamenecka, Theodore
Kissil, Joseph
Luo, Junli
McDonald, Patricia
Miller, Courtney
Niedernhofer, Laura
Phinney, Donald G.
Robbins, Paul
Scampavia, Louis
Schimmel, Paul
Smith, Roy
Spicer, Timothy


Affiliated Faculty

Cline, Hollis
Kojetin, Douglas
Lairson, Luke
Paegel, Brian
Rumbaugh, Gavin
Shen, Ben
Solt, Laura A
Su, Andrew
Wu, Chunlei


Adjunct Faculty