Deborah Chadee, PhD.
Postdoctoral Research Fellow, Massachusetts General Hospital and Tufts Medical Center
Ph.D. University of Manitoba, Canada 1999
Phone No: 419.530.5077
Mitogen-activated protein kinase (MAPK) signaling pathways respond to diverse stimuli and regulate biological processes such as proliferation, migration, differentiation and motility. Our studies are focused on the Mixed Lineage Kinases (MLKs), which are MAPK kinase kinases (MAP3Ks) that activate multiple MAPK pathways. The long-term research goals include deciphering how MLKs are regulated by growth factors and stress stimuli in normal and neoplastic cells, and determining how altered regulation of MLKs and MAPK signaling pathways affects proliferation, invasion, migration and apoptosis in cancer cells.
Current Laboratory Grants:
NIH R15 (09/09/16-08/31/19)
Regulation of MLK3 by oxidative stress in colon cancer cells
Goh, Q., Dearth, C.L., Corbett, J.T., Pierre, P., Chadee, D.N., Pizza, F.X. (2015) Intercellular adhesion molecule-1 expression by skeletal muscle cells augments myogenesis. Exp Cell Res., Feb 15;331(2):292-308.
Blessing, N.A., Brockman A.L.*, and Chadee DN. (2014) The E3 Ligase CHIP Mediates Ubiquitination and Degradation of Mixed-Lineage Kinase 3. Mol Cell Biol. Aug 15;34(16):3132-43.
Chadee, D.N. (2013) Involvement of mixed lineage kinase 3 in cancer. Canadian Journal of Physiology and Pharmacology, Apr;91(4):268-74.
Zhan, Y., Abi Saab, W.F., Modi, N., Stewart, A.M., Liu, J., and Chadee, D.N. (2012) Mixed lineage kinase 3 is required for matrix metalloproteinase expression and invasion in ovarian cancer cells. Exp Cell Res. 318:1641-48.
Abi Saab, W.F., Brown, M.S., and Chadee, D.N. (2012) MLK4β functions as a negative
regulator of MAPK signaling and cell invasion. Oncogenesis. 1:1-6.
Zhan, Y., Modi, N., Stewart, A.M., Hieronimus, R.L., Liu, J., Gutmann, D.H. and Chadee, D.N. (2011) Regulation of mixed lineage kinase 3 is required for neurofibromatosis-2-mediated growth suppression in human cancer. Oncogene, 30(7):781-9.
Zhan, Y. and Chadee D.N. (2010) Inhibition of Cdc42-mediated activation of mixed lineage
kinase 3 by the tumor suppressor protein merlin. Small GTPases, Extra View, 1(3):183-6.
Chadee D.N. and Kyriakis, J.M. (2010) Activation of SAPK/JNKs in vitro. Methods Mol Biol., 661:59-73.
Cole, E.T., Zhan, Y., Abi Saab, W.F., Korchnak, A., Ashburner, B.P., and Chadee, D.N. (2009) Mixed lineage kinase 3 negatively regulates IKK activity and enhances etoposide-induced cell death. Biochimica et Biophysica Acta- Molecular Cell Research. Dec;1793 (12):1811-8.
Korchnak, A.C., Zhan, Y., Aguilar, M.T., and Chadee, D.N. (2009) Cytokine-induced activation of mixed lineage kinase 3 requires TRAF2 and TRAF6. Cell Signal. Nov; 21(11):1620-5.
Kosik A., Bekier M.E., Katusin J.D., Kaur, H., Zhou, X., Diakonova, M., Chadee, D.N. and Taylor, W.R. (2009) Investigating the role of Aurora kinases in RAS signaling. J. Cell. Biochem. Jan 1;106(1):33-41.
Chadee, D.N., Xu, D., Hung, G., Andalibi, A., Lim, D.J., Luo, Z., Gutmann, D.H., and Kyriakis, J.M. (2006) MLK3 regulates B-Raf through a mechanism that involves maintenance of the B-Raf/Raf-1 complex and inhibition by the NF2 tumor suppressor protein. Proc. Natl. Acad. Sci. U S A. Mar 21, 103(12):4463-8.
Chadee, D.N., and Kyriakis, J.M. (2004) A novel role for MLK3 in B-Raf activation and cell proliferation. Cell Cycle, 3(10):1227-29.
Chadee, D.N., and Kyriakis, J.M. (2004) MLK3 is required for mitogen activation of B-Raf, ERK, and cell proliferation. Nat. Cell Biol., 6(8):770-6.
Kyriakis, J.M., Liu, H., and Chadee, D.N. (2004) Activation of SAPKs/JNKs and p38s in vitro. Methods Mol. Biol., 250:61-88.
Roelen, B.A., Cohen, O.S., Raychowdhury, M.K., Chadee, D.N., Zhang, Y., Kyriakis, J.M., Alessandrini, A.A., and Lin, H.Y. (2003) Phosphorylation of threonine 276 in Smad4 is involved in transforming growth factor-beta-induced nuclear accumulation. Am. J. Physiol. Cell Physiol., 285(4):C823-30.
Chadee, D.N., Peltier, C.P., and Davie, J.R. (2002) Histone H1(S)-3 phosphorylation in Ha-ras oncogene-transformed mouse fibroblasts. Oncogene, 21(55):8397-403.
Chadee, D.N., Yuasa, T., and Kyriakis, J.M. (2002) Direct activation of mitogen-activated protein kinase kinase kinase MEKK1 by the Ste-20p homologue GCK and the adapter protein TRAF2. Mol. Cell. Biol., 22:737-749.
Davie, J.R., Samuel, S.K., Spencer, V.A., Holth, L.T., Chadee, D.N., Peltier, C.P., Sun, J.M., Chen, H.Y., and Wright, J.A. (1999) Organization of chromatin in cancer cells: role of signalling pathways. Biochem. Cell. Biol., 77:265-75.
Chadee, D.N., Hendzel, M.J., Tylipski, C.P., Allis, C.D., Bazett-Jones, D.P., Wright, J.A., and Davie, J.R. (1999) Increased Ser-10 phosphorylation of histone H3 in oncogene-transformed and mitogen-stimulated mouse fibroblasts. J. Biol. Chem., 274:24914-20.
Davie, J.R., and Chadee, D.N. (1998) Regulation and regulatory parameters of histone modifications. J. Cell. Biochem., 30/31:203-213.
Holth, L.T., Chadee, D.N., Spencer, V., Samuel, S.K., Safneck, J., and Davie J.R. (1998) Chromatin, nuclear matrix and the cytoskeleton: role of cell structure in neoplastic transformation. Int. J. Oncology, 13:827-837.
Fischer, A.H., Chadee, D.N., Wright, J.A., Gansler, T.S., and Davie, J.R. (1998) A Ras-associated nuclear structural change appears functionally significant and independent of the mitotic signalling pathway. J. Cell. Biochem., 70:130-140.
Chadee, D.N., Allis C.D., Wright, J.A., and Davie. J.R. (1997) Histone H1b phosphorylation is dependent upon ongoing transcription and replication in normal and ras-transformed mouse fibroblasts. J. Biol. Chem., 272:8113-8116.
Taylor, W.R., Chadee, D.N., Allis, C.D., Wright, J.A., and Davie, J.R. (1995) Fibroblasts transformed by combinations of ras, myc, and mutant p53 exhibit increased phosphorylation of histone H1 that is independent of metastatic potential. FEBS Lett., 377:51-53.
Chadee, D.N., Taylor, W.R., Hurta, R.A., Allis, C.D., Wright, J.A., and Davie, J.R. (1995) Increased phosphorylation of histone H1 in mouse fibroblasts transformed with oncogenes or constitutively active MAP kinase kinase. J. Biol. Chem., 270:20098-20105.
Armstrong, J.D., Chadee, D.N., and Kunz, B.A. (1994) Roles for the yeast RAD18 and RAD52 DNA repair genes in UV mutagenesis. Mutation Res., 315:218-293.