Joseph Kissil, PhD
Scripps Research Joint Appointments
Research Focus
Studies over the past several years have demonstrated that pathways regulating processes such as cell fate decisions and organ size control, during development, also play pivotal roles during tumorigenesis. While many of the individual signal transduction pathways have been outlined, a major ongoing challenge has been to integrate these findings into a comprehensive map of cellular signaling networks. Our lab is studying the signal transduction pathways regulated by small GTP-binding proteins from the Ras and Rac families and how these pathways crosstalk with pathways controlling cell fate and organ size control, such as the Notch, Wnt and Hpo/YAP pathways.
Education
Ph.D. (Molecular Biology), Weizmann Institute of Science, 1999B.Sc. (Life Sciences), Ben-Gurion University of the Negev, 1993
Professional Experience
2017-2018 Associate Professor, Molecular Medicine, Scripps Research2012-2017 Associate Professor, Cancer Biology, Scripps Research
2011-2012 Associate Professor, Program in Molecular and Cellular Oncogenesis, Wistar Institute
2005-2012 Member, Graduate Group in Cell and Molecular Biology, University of Pennsylvania
2009-2010 Wistar Assistant Professor, Department of Cancer Biology, University of Pennsylvania
2004-2010 Assistant Professor, Program in Molecular and Cellular Oncogenesis, Wistar Institute
2006-2009 Wistar Assistant Professor, Department of Cell and Developmental Biology, University of Pennsylvania
1999-2004 Postdoctoral Fellow with Dr. Tyler Jacks, Massachusetts Institute of Technology
Awards & Professional Activities
1999-2001 "Human Frontier Science Program" Award2001-2003 NF Foundation "Young Investigator Award"
2003-2004 R.L. Kirchstein National Research Service Award
2010-2012 American Cancer Society Research Scholar Award.
2014 Scripps Florida Outstanding Mentor Award
Selected References
Kota, S., Hou, S., Guerrant, W., Madoux, F., Troutman, S., Fernandez-Vega, V., Alekseeva, N., Madala, N., Scampavia, L., Kissil, J.L.# and Spicer, T.P.# (#corresponding authors). “A novel 3-dimenasional high throughput screening approach identifies inducers of a KRAS selective lethal phenotype”. Oncogene (Published online 10 May) 2018.
Chinthalapudi, K., Mandati, V., Zheng, J., Griffin, P., Kissil, J.L., and Izard, T. “Lipid binding promotes the open conformation, membrane localization and tumor-suppressive activity of neurofibromin 2” Nature Communications 9(1338), 2018.
Moleirinho, S.; Hoxha, S.; Mandati, V.; Curtale, G.; Troutman, S.; Ehmer, U.; Kissil, J.L. "Regulation of localization and function of the transcriptional co-activator YAP by angiomotin." Elife. 2017 May 3;6 pii: e23966. doi: 10.7554/eLife.23966
Troutman, S.; Moleirinho, S.; Kota, S.; Nettles, K.; Fallahi, M.; Johnson, G. and Kissil, J.L. "Crizotinib inhibits NF2-associated schwannoma through inhibition of Focal Adhesion Kinase 1" Oncotarget, 7(34):54515-25, 2016.
Guerrant, W; Kota, S; Troutman, S; Mandati, V; Fallahi, M; Stemmer-Rachamimov, A; Kissil, J.L. "YAP Mediates Tumorigenesis in Neurofibromatosis Type 2 by Promoting Cell Survival and Proliferation through a COX-2-EGFR Signaling Axis". Cancer Research, 2016 May 23
Moleirinho, S.; Guerrant, W.; Kissil, J.L. "The Angiomotins – From discovery to function." FEBS Lett. 2014 Feb 15. pii:S0014-5793(14)00125-2. PMCID: PMC4112001
Yi, C., Shen, Z., Stemmer-Rachamimov, A., Dawany, N., Troutman, S., Showe, L.C., Liu, Q., Shimono, A., Sudol, M., Holmgren, L., Stanger, B.Z. and Kissil, J.L. “Angiomotin-p130 is required for Yap-mediated hepatic epithelial cell expansion and tumorigenesis”. Science Signal. 2013 Sep 3;6(291):ra77
Zhou, C., Troutman, S., Maksimoska, J., Liu, Q., Campbell, D., Marmorstein, R. and Kissil, J.L. “FRAX597, a small molecule inhibitor of the p21-activated kinases, inhibits tumorigenesis of NF2-associated schwannomas“.J. Biol. Chem. 288(40):29105-14, 2013.
Licciulli, S., Avila, J.L., Hanlon, L., Troutman, S., Cesaroni, M., Keith, B., Simon, M.C., Pure, E., Radtke, F., Capobianco, A.J. and Kissil, J.L. “Notch1 is required for Kras-induced lung adenocarcinoma and controls tumor cells survival via p53”. Cancer Res. 73(19):5974-84, 2013
Chun, Z., Licciulli, S., Avila, J.L., Cho, M., Troutman, S., Jiang, P., Vachani, A., Albelda, S.M. and Kissil, J.L. “Rac1b, a splice form of Rac1, promotes K-ras-induced lung tumorigenesis”. Oncogene 32(7):903-9, 2012.
Yi C, Troutman S, Fera D, Stemmer-Rachamimov A, Avila J, Christian N, Persson NL, Speicher DW, Shimono A, Marmorstein R, Holmgren L and Kissil J. "A Tight Junction-Associated Merlin-Angiomotin Complex Mediates Merlin’s Regulation of Mitogenic Signaling and Tumor Suppressive Functions" Cancer Cell. 2011 April 19:527-540.
Yi, C. and Kissil, J.L. “Merlin in organ size control and tumorigenesis: Hippo versus EGFR?”. Genes & Dev. 24:1673-80, 2010
Hanlon, L., Avila, J.L., Demarest, R.M., Troutman, S., Allen, M., Ratti, F., Rustgi, A.K., Stanger, B.Z., Radtke, F., Adsay, V., Long, F., Capobianco, A.J. and Kissil, J.L. “Notch1 functions as a tumor suppressor in K-ras-induced pancreatic ductal adenocarcinoma”. Cancer Res. 70: 4280-6, 2010
Santos, A.M., Jung, J., Aziz, N., Kissil, J.L.# and Puré E.# (#Equal contribution). “Targeting the Stroma Cell Protease Fibroblast Activation Protein Inhibits Tumor Growth”. J. Clin. Invest. 119:3613-25, 2009
Yi, C., Wilker, E.W., Yaffe, M.B., Stemmer-Rachamimov, A. and Kissil, J.L. “Validation of the p21-activated kinases as targets for inhibition in neurofibromatosis type 2. Cancer Res. 68:7932-7, 2008