Jan L Christian
PositionProfessor - Cell and Developmental Biology
Research Interests: Signal Transduction Bone Morphogenetic Proteins Growth and Embryonic Development Mouse Models Xenopus laevis Proprotein Convertases Hematopoiesis Extracellular Matrix 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.
Lab MembershipsChristian Neurobiology Laboratory (Principal Investigator/Director)
Professor of Neurobiology & Anatomy and Internal Medicine
University of Utah
Salt Lake City, Utah