Research Interest:
 
Signal transduction, growth control, actin cytoskeleton

Description:

Cell growth (increase in size), usually accompanied by cell division (increase in cell number) gives rise to an organ, organism, or tumor. Growth is orchestrated by signalling events, occuring only at specific times and places. My research objective is to understand how signals generated by the availability of nutrients and hormones coordinate growth and how deregulation of these signals leads to diseases such as cancer, diabetes, cardiovascular and neurological diseases.

The target of rapamycin (TOR) regulates cell growth in response to nutrients. TOR is a protein kinase that displays homology to lipid kinases. It is inhibited by the clinically important drug, rapamycin (used as an immunosuppressant, anti-fungal, to prevent restenosis in coronary stents, and as a potential anti-cancer drug). TOR is part of two distinct protein complexes TORC1 (TOR complex 1) and TORC2. TORC1 regulates protein synthesis in response to nutrient availability, and thus serves as a temporal controller of growth. TORC2 controls actin cytoskeleton organization and thus regulates spatial aspects of growth. Our long-term goal is to understand how the TORCs integrate the temporal and spatial control of growth and thereby gain insight as to how defective cellular growth and actin-based migration can lead to diseases.

Since the TOR complexes are highly conserved from yeast to mammals, our studies address growth signalling mechanisms in both yeast and mammalian cells. We use a combination of genetic, biochemical, cell and molecular biological techniques to understand TOR signalling.

Publications:

Facchinetti V, Ouyang W, Wei H, Soto N, Lazorchak A, Gould C, Lowry C, Newton AC, Mao Y, Miao RQ, Sessa WC, Qin J, Zhang P, Su B, Jacinto E. (2008) The mammalian target of rapamycin complex 2 controls folding and stability of Akt and protein kinase C. EMBO J. J27(14):1932-43.

Jacinto E. (2008) What controls TOR? IUBMB Life. 60(8):483-96. Review.

Jacinto E, Lorberg A. (2008) TOR regulation of AGC kinases in yeast and mammals. Biochem J. 410(1):19-37. Review.

Jacinto E. (2007) Phosphatase targets in TOR signaling. Methods Mol Biol. 365:323-34.

Jacinto E, Facchinetti V, Liu D, Soto N, Wei S, Jung SY, Huang Q, Qin J, Su B. (2006)SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity. Cell. 2006 Oct 6;127(1):125-37.

Jacinto, E., Loewith, R., Schmidt, A., Lin, S., Ruegg, M.A., Hall, A., and Hall, M.N. (2004). Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nature Cell Biol. 6, 1122-1128.

Jacinto, E., and Hall, M.N. (2003). TOR signaling in bugs, brain, and brawn. Nature Reviews (Mol.Cell.Biol) 4, 117-126.

Loewith, R., Jacinto, E., Wullschleger, S., Lorberg, A., Crespo, J.L., Bonenfant, D., Oppliger, W., Jenoe, P., and Hall, M.N. (2002). Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Molecular Cell 10, 457-468.

Bonenfant, D., Schmelzle, T., Jacinto, E., Crespo, J.L., Mini, T., Hall, M.N., and Jenoe, P. (2003). Quantitation of changes in site specific phosphorylation: a simple method based on stable isotope labelling and mass spectrometry. Proc. Natl. Acad. Sci., 100, 880-885.

Jacinto, E., Guo, B., Arndt, K.T., Schmelzle, T., and Hall, M.N. (2001). TIP41 interacts with TAP42 and negatively regulates the TOR signaling pathway. Molecular Cell 8, 1017-1026.

Jacinto, E., Werlen G., and Karin, M. (1998). Cooperation between Syk and Rac1 leads to synergistic JNK activation in T lymphocytes. Immunity 8, 31-41.