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Research

Cell-cell signaling molecules such as bone morphogenetic proteins (BMPs) and Wnts play critical roles in specifying cell fate during vertebrate embryogenesis. Strict regulation of BMP and Wnt activity is required to prevent congenital anomalies, degenerative diseases and cancer. Our research program has two major foci:

1) Understanding how BMP activity is regulated by proteolysis of an inactive precursor molecule. We use targeted mutagenesis in mice together with cell biological and biochemical approaches in Xenopusembryos to determine how cleavages within the inactive prodomain of BMP precurosor proteins regulates intracellular trafficking and activity of mature BMP homodimers and heterodimers.

2) Analysis of secreted signaling molecules required for blood development. Our studies suggest that BMPs  signal to embryonic ectodermal cells to activate expression of a secreted protein that signals to the mesoderm to allow for specification and survival of primitive blood progenitors.  We have used a microarray based approach to identify multiple novel gene products and signaling pathways that function downstream of BMPs in this process and are currently studying their roles during hematopoiesis. One protein of particular interest is a novel transmembrane protein that regulates the balance between non-canonical and canonical Wnt signaling during hematopoiesis, and most likely throughout development and adult homeostasis.

Selected Publications

Search Pubmed for Jan Christian's lab publications

Kwon, S., and Christian, J.L. (2011) Sortilin associates with TGF-ß family proteins to enhance lysosome-mediated degradation, J. Biol. Chem., 286:21876.

Sopory, S., Kwon, S., Wehrli, M. and Christian, J.L. (2010). Regulation of Decapentaplegic activity by tissue-specific cleavage of an upstream sitewithin the prodomain, Developmental Biology, 346:102-12.

Nelsen, S.M. and Christian, J.L. (2009) Site-specific cleavage of Bone morphogenetic protein4 (BMP4) by furin, PC6 and PC7, J.Biol. Chem, 284:27157-66.

Goldman, D.C., Bailey, A.S., Pfaffle, D.L., Masri, A., Christian, J.L., and  Fleming, W.H. (2009) BMP4 Regulates Adult Hematopoietic Stem Cell Maintenance in vivo, Blood, 114:4393-401.

Goldman, D.C. Donley N.. and Christian, J.L. (2009) Genetic interaction between Bmp2 and Bmp4 reveals shared functions during multiple aspects of mouse organogenesis, Mech Dev, 126, 117-27.

Dalgin, G., Ahmed, R., Goldman, D.C. and Christian, J.L. (2007) GATA-2 functions downstream of BMPs and CaM KIV in ectodermal cells during primitive hematopoiesis. Dev. Biol, 310, 454-469.

Goldman, D.C., Berg, L.K., Heinrichs, M., and Christian. J.L. (2006). Blood. 107, 3114-3121.

Goldman, Hackenmiller, R., Nakayama, T., Sopory, S., Wong, C., Kulessa, H. and Christian, J.L. (2006) Mutation of an upstream cleavage site in the BMP4 prodomain leads to tissue-specific loss of activity. Development,133, 1933-1942.

Sopory, S., Nelsen, S., Degnin, C., Wong. C. and Christian, J.L. (2006) Regulation of BMP-4 protein by sequence elements within the prodomain. J. Biol. Chem. 281, 34021-34031.