Jan L. Christian, PhD
- Bone Morphogenetic Proteins
- Growth and Embryonic Development
- Marfan Syndrome
- Mouse Models
- Xenopus laevis
- Proprotein Convertases
- Cardiovascular Aspects of Marfan syndrome
- 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) play critical roles in specifying cell fate during vertebrate embryogenesis. Strict regulation of BMP activity is required 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. One current project in the lab involves analysis of mice carrying a point mutation that prevents cleavage of BMP7. This cleavage mutant mouse dies early in development due to defects in the heart and other organs that are caused by the combined loss of BMP7 and other BMP family members that normally heterodimerize with BMP7. We are using genetic interaction screens and biochemical assays to find out which BMP family members heterodimerize with BMP7 in vivo.A second project investigates genetic interactions between the extracellular matrix molecule, Fibrillin1, and BMP4. Mutations in fibrillin1 underlie the human genetic disorder, Marfan syndrome, which leads to pulmonary fibrosis and aortic aneurysm. Our studies show that the BMP4 prodomain functions to regulate BMP activity through interactions with Fibrillin1, and that loss of these interactions play a causal role in Marfan syndrome. We are trying to understand the molecular mechanisms by which BMP4 and Fibrillins cross regulate each others function.2) Analysis of novel proteins that function downstream of BMPs during hematopoeisis and other developmental processes. We have used a microarray based approach to identify multiple novel gene products and signaling pathways that function downstream of BMPs in blood development. One protein of particular interest is a novel transmembrane protein that is required not only for blood formation but also for formation of the central nervous system and other dorsal structures. We are trying to understand how this protein transduces signals from the membrane to the nucleus to control early development.
|Postdoctoral Fellowship||University of Washington School of Medicine, Department of Pharmacology
|Doctoral Training||University of Washington School of Medicine
Pharmacology, Molecular and Cellular Developmental Biology
|Undergraduate||Southern Oregon University
|Other Training||University of Nebraska
- 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.
- Kwon S, Christian JL (2011). Sortilin associates with TGF-ß family proteins to enhance lysosome-mediated degradation. J Biol Chem, 286, 21876-21885.
- 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, 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.
- Nelsen SM, Christian JL (2009). Site-specific cleavage of BMP4 by furin, PC6, and PC7. J Biol Chem, 284(40), 27157-66.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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]. Wiley Interdisciplinary Reviews: 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).