Jan L. Christian, PhD
- Signal Transduction
- Bone Morphogenetic Proteins
- Growth and Embryonic Development
- Mouse Models
- Xenopus laevis
- Proprotein Convertases
- Extracellular Matrix
- Departments: Internal Medicine - Professor, Neurobiology & Anatomy - Professor
- Divisions: Hematology/BMT
- Cancer Center Programs: Cell Response & Regulation
Academic Office Information
Biomedical Polymers Research Bldg
20 S 2030 E, Room: 308B
Salt Lake City, UT 84112
Cell-cell signaling molecules such as bone morphogenetic proteins (BMPs) and nodals, play critical roles in specifying cell fate during vertebrate embryogenesis. Their activity must be strictly regulated to prevent birth defects, degenerative diseases and cancer. Our research program has two major foci:
1) Understanding how BMP activity is regulated by cleavage of the precursor protein and by interactions with the extracellular matrix. We use targeted mutagenesis in mice together with cell biological and biochemical approaches in Xenopus embryos to determine how cleavages within the inactive prodomain of the BMP precursor protein regulate the activity of mature BMP homodimers and heterodimers. We are also studying how point mutations within the prodomain of BMP4, which are associated with congenital birth defects in humans, impact BMP homodimer and heterodimer formation or function.
2) Analysis of signal transduction downstream of Tril. We discovered that the novel transmembrane protein Tril is required not only for blood formation but also for formation of the central nervous system, and that it does so by coordinately regulating nodal and BMP signaling in the embryo. In adults, Tril functions as a co-receptor for Toll-like receptors (Tlrs), which recognize foreign pathogens and mount an immune response. We are studying how this protein transduces signals from the membrane to the nucleus to control early development, and have discovered several new players in the signaling cascade activated by Tril in embryos.
|Doctoral Training||University of Washington School of Medicine
Pharmacology, Molecular and Cellular Developmental Biology
- Kim, H-S, McKnite, A, Xie, Y and Christian, JL (2018). Fibronectin type III and intracellular domains of Toll-like receptor 4 interactor with leucine-rich repeats (Tril) are required for developmental signaling. Mol Biol Cell, 29, 523-531.
- Green, YS, Mimoto, MS, Kwon, S, Xi, Y and Christian, JL (2016). Tril targets Smad7 for degradation to allow for hematopoietic specification in Xenopus embryos. Development, 143, 4016-4026.
- Mimoto, MS, Kwon, S, Green, YS, Goldman, D, and Christian, JL (2015). GATA2 regulates Wnt signaling to promote primitive red blood cell fate. Dev Biol, 407, 1-11.
- Neugebauer JM, Kwon S, Kim HS, Donley N, Tilak A, Sopory S, Christian JL (2015). The prodomain of BMP4 is necessary and sufficient to generate stable BMP4/7 heterodimers with enhanced bioactivity in vivo. Proc Natl Acad Sci U S A, 112(18), E2307-16.
- Tilak, A, Nelsen, S, Kim, H, Donley, N McKnite, A, Lee, H and Christian, J (2014). Simultaneous rather than ordered cleavage of the BMP4 prodomain leads to ligand loss in mice. Development, 141, 3062-3071.
- Mimoto M, Christian JL (2012). Friend of GATA (FOG) Interacts with the Nucleosome Remodeling and Deacetylase Complex (NuRD) to Support Primitive Erythropoiesis in Xenopus laevis. PLoS ONE, 7(1), e29882.
- Kwon S, Christian JL (2011). Sortilin associates with transforming growth factor-beta family proteins to enhance lysosome-mediated degradation. J Biol Chem, 286(24), 21876-85.
- Sopory S, Kwon S, Wehrli M, Christian JL (2010). Regulation of Dpp activity by tissue-specific cleavage of an upstream site within the prodomain. Dev Biol, 346(1), 102-12.
- Goldman DC, Bailey AS, Pfaffle DL, Al Masri A, Christian JL, Fleming WH (2009). BMP4 regulates the hematopoietic stem cell niche. Blood, 114(20), 4393-401.
- Nelsen SM, Christian JL (2009). Site-specific cleavage of BMP4 by furin, PC6, and PC7. J Biol Chem, 284(40), 27157-66.
- Goldman DC, Donley N, Christian JL (2009). Genetic interaction between Bmp2 and Bmp4 reveals shared functions during multiple aspects of mouse organogenesis. Mech Dev, 126(3-4), 117-27.
- Dalgin G, Goldman DC, Donley N, Ahmed R, Eide CA, Christian JL (2007). GATA-2 functions downstream of BMPs and CaM KIV in ectodermal cells during primitive hematopoiesis. Dev Biol, 310(2), 454-69.
- Goldman DC, Hackenmiller R, Nakayama T, Sopory S, Wong C, Kulessa H, Christian JL (2006). Mutation of an upstream cleavage site in the BMP4 prodomain leads to tissue-specific loss of activity. Development, 133(10), 1933-42.
- Goldman DC, Berg LK, Heinrich MC, Christian JL (2006). Ectodermally derived steel/stem cell factor functions non-cell autonomously during primitive erythropoiesis in Xenopus. Blood, 107(8), 3114-21.
- Sopory S, Nelsen S, Degnin C, Wong C, Christian JL (2006). Regulation of BMP-4 protein by sequence elements within the prodomain. J Biol Chem, 281, 34021-34031.
- Birsoy B, Berg L, Williams PH, Smith JC, Wylie CC, Christian JL, Heasman J (2005). XPACE4 is a localized pro-protein convertase required for mesoderm induction and the cleavage of specific TGFbeta proteins in Xenopus development. Development, 132(3), 591-602.
- Degnin C, Jean F, Thomas G, Christian JL (2004). Cleavages within the prodomain direct intracellular trafficking and degradation of mature bone morphogenetic protein-4. Mol Biol Cell, 15(11), 5012-20.
- Walters MJ, Wayman GA, Notis JC, Goodman RH, Soderling TR, Christian JL (2002). Calmodulin-dependent protein kinase IV mediated antagonism of BMP signaling regulates lineage and survival of hematopoietic progenitors. Development, 129(6), 1455-66.
- Cui Y, Hackenmiller R, Berg L, Jean F, Nakayama T, Thomas G, Christian JL (2001). The activity and signaling range of mature BMP-4 is regulated by sequential cleavage at two sites within the prodomain of the precursor. Genes Dev, 15(21), 2797-802.
- Wayman GA, Walters MJ, Kolibaba K, Soderling TR, Christian JL (2000). CaM kinase IV regulates lineage commitment and survival of erythroid progenitors in a non-cell-autonomous manner. J Cell Biol, 151(4), 811-24.
- Cui Y, Jean F, Thomas G, Christian JL (1998). BMP-4 is proteolytically activated by furin and/or PC6 during vertebrate embryonic development. EMBO J, 17(16), 4735-43.
- Nakayama T, Snyder MA, Grewal SS, Tsuneizumi K, Tabata T, Christian JL (1998). Xenopus Smad8 acts downstream of BMP-4 to modulate its activity during vertebrate embryonic patterning. Development, 125(5), 857-67.
- Nakao A, Afrakhte M, Moren A, Nakayama T, Christian JL, Heuchel R, Itoh S, Kawabata M, Heldin NE, Heldin CH, ten Dijke P (1997). Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling. Nature, 389(6651), 631-5.
- Tsuneizumi K, Nakayama T, Kamoshida Y, Kornberg TB, Christian JL, Tabata T (1997). Daughters against dpp modulates dpp organizing activity in Drosophila wing development. Nature, 389(6651), 627-31.
- Cui Y, Tian Q, Christian JL (1996). Synergistic effects of Vg1 and Wnt signals in the specification of dorsal mesoderm and endoderm. Dev Biol, 180(1), 22-34.
- Christian JL, Moon RT (1993). Interactions between Xwnt-8 and Spemann organizer signaling pathways generate dorsoventral pattern in the embryonic mesoderm of Xenopus. Genes Dev, 7(1), 13-28.
- Christian JL, Olson DJ, Moon RT (1992). Xwnt-8 modifies the character of mesoderm induced by bFGF in isolated Xenopus ectoderm. EMBO J, 11(1), 33-41.
- Sokol S, Christian JL, Moon RT, Melton DA (1991). Injected Wnt RNA induces a complete body axis in Xenopus embryos. Cell, 67(4), 741-52.
- Olson DJ, Christian JL, Moon RT (1991). Effect of wnt-1 and related proteins on gap junctional communication in Xenopus embryos. Science, 252(5009), 1173-6.
- Christian JL, McMahon JA, McMahon AP, Moon RT (1991). Xwnt-8, a Xenopus Wnt-1/int-1-related gene responsive to mesoderm-inducing growth factors, may play a role in ventral mesodermal patterning during embryogenesis. Development, 111(4), 1045-55.
- Christian, JL and Heldin, C-H (2017). The TGFß superfamily in Lisbon: navigating through development and disease. [Review]. Development, 144, 4476-4480.
- Christian JL (2012). Morphogen gradients in development: from form to function. [Review]. WIREs Developmental Biology, 1, 3-15.
- Moon RT, Christian JL (1992). Competence modifiers synergize with growth factors during mesoderm induction and patterning in Xenopus. [Review]. Cell, 71(5), 709-12.
- Sopory S, Christian JL (2006). Regulation of TGF-ß family activity by proprotein processing. In Whitman M, Sater A (Eds.), Analysis of Growth Factor signaling in embryos, Methods in Signal Transduction (pp. 37-60).
- Goldman D, Christian JL (2004). Cell Signaling during early hematopoietic development. In Meyers RA (Ed.), Encyclopedia of Molecular Cell Biology and Molecular Medicine (pp. 429-450).