Return to Faculty ListingBrian Schutte Ph.D.
brian-schutte
 uiowa edu Associate Professor of Pediatrics
Selected Publications
*Kondo, S *BC Schutte, RJ Richardson, BC Bjork, AS Knight, Y Watanabe, E Howard, RL Ferreira De Lima, S Daack-Hirsch, A Sander, DM McDonald-McGinn, EH Zackai, EJ Lammer, AS Aylsworth, HH Ardinger, AC Lidral, BR Pober, L Moreno, M Arcos-Burgos, C Valencia, C Houdayer, M Bahuau, D Moretti-Ferreira, A Richieri-Costa, MJ Dixon, JC Murray Murray, JC and BC Schutte (2004) Cleft palate, pathways and pursuits. J. Clin. Invest. 113: 1676-1678 Zucchero, TM, ME Cooper, BS Maher, S Daack-Hirsch B Nepomuceno, L Ribeiro, DCaprau, K Christensen, Y Suzuki, J Machida, N Natsume, K Yoshiura, AR. Vieira, IM. Orioli, EE. Castilla, L Moreno, M Arcos-Burgos AC. Lidral, LL Field, Y Liu, A Ray, TH Goldstein, RE Schultz,,M Shi, S Kondo, BC Schutte, ML Marazita, JC Murray (2004) Interferon Regulatory Factor 6 (IRF6) is a Modifier for Isolated Cleft Lip and Palate. N. Engl. J. Med. 351: 769-780 Bailey, CM, Z Khalkhali-Ellis, S Kondo, N. Margaryan, RE Seftor, WW Wheaton, S Amir, MR Pins, BC Schutte, MJ Hendrix (2005) Maspin binds directly to interferon regulatory factor 6: Identification of a novel serpin partnership. J. Biol. Chem. 280: 34210-34217. Knight, A.S., BC Schutte, R Jiang, & MJ Dixon (2005) Developmental expression analysis of the mouse and chick orthologues of IRF6: The gene mutated in Van der Woude syndrome. Dev. Dyn. 2235: 1441-1447. Ingraham, CR, A Kinoshita, S Kondo, B Yang, S Sajan, KJ Trout, MI Malik, M Dunnwald, SL Goudy, M Lovett, JC Murray & BC Schutte (2006) Abnormal skin, limb and craniofacial morphogenesis in mice deficient for interferon regulatory factor 6 (Irf6). Nat. Genet. 38:1335-1340.
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The goal of my lab is to determine the genes and pathways that are essential for craniofacial development. An important step in craniofacial development is the fusion of the two palatal shelves that grow out from the maxillary prominence and fuse to form a seamless palate. Failure of the palates to fuse causes an orofacial cleft in the lip and/or palate. Cleft lip and palate is a complex disorder and is one of the most common birth defects in humans with a prevalence of 1/1000 live births. Recently, my lab, in collaboration with other labs, discovered that mutations in Interferon Regulatory Factor 6 (IRF6) cause two related orofacial clefting disorders, Van der Woude syndrome (VWS; OMIM119300) and popliteal pterygium syndrome (PPS; OMIM119500). IRF6 is expressed in the epithelial cells at the medial edge of the palate shelves, the site of fusion. The medial edge epithelia (MEE) are critical for palate fusion. The MEE from the two opposed palates must adhere to each other and then eventually disappear to allow an unbroken bridge of mesenchymal tissue that will form the underlying cartilage and muscle. The MEE disappear using three pathways, migration to oral and nasal epithelium, apoptosis and epithelium to mesenchymal transformation. The IRFs encode transcription factors that are involved in the activation of the interferon genes (hence the name), but also in regulating cell growth, death and differentiation. We are using genetic, molecular genetic and molecular biological approaches to determine the role of IRF6 in the pathways that contribute to the MEE adhesion and disappearance. We note that these pathways are also used in the development of other tissues such as skin, limbs and genitalia. The flip side of these pathways is un-regulated growth that could lead to cancer. My lab is also exploring a potential link between IRF6 and invasiveness of tumors.