ZFIN ID: ZDB-PERS-050519-11
Jette, Cicely A.
Email: Cicely.Jette@hci.utah.edu
URL: http://www.huntsmancancer.org/research/cancer-investigators/jette-cicely
Affiliation: Cicely Jette Lab
Address: Huntsman Cancer Institute 2000 Circle of Hope SLC UT 84112 USA
Country: United States
Phone: 801-587-5568

The majority of current cancer treatments, which include radiotherapy and most chemotherapies, elicit cancer cell death through the induction of excessive DNA damage, the premise being that defects in the DNA damage response (DDR) pathway make cancer cells more susceptible to the lethal effects of DNA damage. However, mutations in the DDR pathway that hinder DNA-damage induced apoptosis, such as those that impair the pro-apoptotic tumor suppressor p53 or upregulate the anti-apoptotic oncogene Bcl-2, can also form the basis for resistance to cancer therapy. The goal of the Jette Lab is to discover therapeutic targets whose inhibition restores normal cell death pathways to cancer cells that are resistant to DNA-damaging agents. Using a forward genetic approach, we have identified a number of recessive mutations that give rise to radiosensitization phenotypes during zebrafish development. These mutations re-sensitize bcl-2-overexpressing cells to pro-apoptotic stimuli, and importantly, they represent genes with novel roles in the DDR pathway. We are currently dissecting the function of these genes in the DDR pathway through genetic epistasis analysis in zebrafish embryos, biochemical analysis in human cell culture, and ability of the mutations to sensitize bcl-2-overexpressing zebrafish T-cell tumors to radiation-induced apoptosis.

Sorrells, S., Nik, S., Casey, M., Cameron, R.C., Truong, H., Toruno, C., Gulfo, M., Lowe, A., Jette, C., Stewart, R.A., Bowman, T.V. (2018) Spliceosomal components protect embryonic neurons from R-loop-mediated DNA damage and apoptosis. Disease models & mechanisms. 11(2)
Liu, X., Li, Y.S., Shinton, S.A., Rhodes, J., Tang, L., Feng, H., Jette, C.A., Look, A.T., Hayakawa, K., Hardy, R.R. (2017) Zebrafish B Cell Development without a Pre-B Cell Stage, Revealed by CD79 Fluorescence Reporter Transgenes. Journal of immunology (Baltimore, Md. : 1950). 199(5):1706-1715
Boer, E.F., Jette, C.A., Stewart, R.A. (2016) Neural Crest Migration and Survival Are Susceptible to Morpholino-Induced Artifacts. PLoS One. 11:e0167278
Modzelewska, K., Boer, E.F., Mosbruger, T.L., Picard, D., Anderson, D., Miles, R.R., Kroll, M., Oslund, W., Pysher, T.J., Schiffman, J.D., Jensen, R., Jette, C.A., Huang, A., Stewart, R.A. (2016) MEK Inhibitors Reverse Growth of Embryonal Brain Tumors Derived from Oligoneural Precursor Cells. Cell Reports. 17:1255-1264
Jimenez, L., Wang, J., Morrison, M.A., Whatcott, C., Soh, K.K., Warner, S., Bearss, D., Jette, C.A., Stewart, R.A. (2016) Phenotypic chemical screening using zebrafish neural crest reporters identifies retinoid acid as an inhibitor of epithelial morphogenesis. Disease models & mechanisms. 9(4):389-400
Harrold, I., Carbonneau, S., Moore, B.M., Nguyen, G., Anderson, N.M., Saini, A.S., Kanki, J.P., Jette, C.A., Feng, H. (2016) Efficient transgenesis mediated by pigmentation rescue in zebrafish. Biotechniques. 60:13-20
Boer, E.F., Howell, E.D., Schilling, T.F., Jette, C.A., Stewart, R.A. (2015) Fascin1-Dependent Filopodia are Required for Directional Migration of a Subset of Neural Crest Cells. PLoS Genetics. 11:e1004946
Toruno, C., Carbonneau, S., Stewart, R.A., and Jette, C. (2014) Interdependence of Bad and Puma during ionizing-radiation-induced apoptosis. PLoS One. 9(2):e88151
Sorrells, S., Toruno, C., Stewart, R.A., and Jette, C. (2013) Analysis of apoptosis in zebrafish embryos by whole-mount immunofluorescence to detect activated Caspase 3. Journal of visualized experiments : JoVE. (82):e51060
Sorrells, S., Carbonneau, S., Harrington, E., Chen, A.T., Hast, B., Milash, B., Pyati, U., Major, M.B., Zhou, Y., Zon, L.I., Stewart, R.A., Look, A.T., and Jette, C. (2012) Ccdc94 Protects Cells from Ionizing Radiation by Inhibiting the Expression of p53. PLoS Genetics. 8(8):e1002922
Pyati, U.J., Gjini, E., Carbonneau, S., Lee, J.S., Guo, F., Jette, C.A., Kelsell, D.P., and Look, A.T. (2011) p63 Mediates an Apoptotic Response to Pharmacological and Disease-Related ER Stress in the Developing Epidermis. Developmental Cell. 21(3):492-505
Feng, H., Stachura, D.L., White, R.M., Gutierrez, A., Zhang, L., Sanda, T., Jette, C.A., Testa, J.R., Neuberg, D.S., Langenau, D.M., Kutok, J.L., Zon, L.I., Traver, D., Fleming, M.D., Kanki, J.P., and Look, A.T. (2010) T-lymphoblastic lymphoma cells express high levels of BCL2, S1P1, and ICAM1, leading to a blockade of tumor cell intravasation. Cancer Cell. 18(4):353-366
Langenau, D.M., Keefe, M.D., Storer, N.Y., Jette, C.A., Smith, A.C., Ceol, C.J., Bourque, C., Look, A.T., and Zon, L.I. (2008) Co-injection strategies to modify radiation sensitivity and tumor initiation in transgenic Zebrafish. Oncogene. 27(30):4242-4248
Jette, C.A., Flanagan, A.M., Ryan, J., Pyati, U.J., Carbonneau, S., Stewart, R.A., Langenau, D.M., Look, A.T., and Letai, A. (2008) BIM and other BCL-2 family proteins exhibit cross-species conservation of function between zebrafish and mammals. Cell death and differentiation. 15(6):1063-1072
Sidi, S., Sanda, T., Kennedy, R.D., Hagen, A.T., Jette, C.A., Hoffmans, R., Pascual, J., Imamura, S., Kishi, S., Amatruda, J.F., Kanki, J.P., Green, D.R., D'Andrea, A.A., and Look, A.T. (2008) Chk1 Suppresses a Caspase-2 Apoptotic Response to DNA Damage that Bypasses p53, Bcl-2, and Caspase-3. Cell. 133(5):864-877
Chen, J., Jette, C., Kanki, J.P., Aster, J.C., Look, A.T., and Griffin, J.D. (2007) NOTCH1-induced T-cell leukemia in transgenic zebrafish. Leukemia. 21(3):462-471
Berghmans, S., Jette, C., Langenau, D., Hsu, K., Stewart, R., Look, T., and Kanki, J.P. (2005) Making waves in cancer research: new models in the zebrafish. Biotechniques. 39(2):227-237
Langenau, D.M., Jette, C., Berghmans, S., Palomero, T., Kanki, J.P., Kutok, J.L., and Look, A.T. (2005) Suppression of apoptosis by bcl-2-overexpression in lymphoid cells of transgenic zebrafish. Blood. 105(8):3278-3285