Research Topics
Genomes and Genes
| Raphael KopanSummaryAffiliation: Washington University School of Medicine Country: USA Publications
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Detail Information
Publications
Aph-2/Nicastrin: an essential component of gamma-secretase and regulator of Notch signaling and Presenilin localizationRaphael Kopan
Department of Pharmacology and Molecular Biology, Washington University School of Medicine, St Louis, MO 63110, USA
Neuron 33:321-4. 2002..The transmembrane protein Nicastrin has been found to associate with Presenilin, Notch, and APP. Recent biochemical and genetic studies have focused on elucidating the function of this protein...
The contribution of Notch1 to nephron segmentation in the developing kidney is revealed in a sensitized Notch2 background and can be augmented by reducing Mint dosageKameswaran Surendran
Department of Developmental Biology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
Dev Biol 337:386-95. 2010....- Analysis of Notch function in presomitic mesoderm suggests a gamma-secretase-independent role for presenilins in somite differentiationStacey S Huppert
Department of Molecular Biology and Pharmacology, Division of Dermatology, Washington University School of Medicine, St Louis, Missouri 63110, USA
Dev Cell 8:677-88. 2005..These data clarify multiple roles for Notch signaling during segmentation and suggest that the earliest stages of somitogenesis are regulated by both Notch-dependent and Notch-independent functions of presenilin... - gamma-secretase functions through Notch signaling to maintain skin appendages but is not required for their patterning or initial morphogenesisYonghua Pan
Department of Molecular Biology and Pharmacology, Division of Dermatology, Washington University School of Medicine, Box 8103, 660 South Euclid Avenue, St Louis, MO 63110, USA
Dev Cell 7:731-43. 2004.... - Notch-deficient skin induces a lethal systemic B-lymphoproliferative disorder by secreting TSLP, a sentinel for epidermal integrityShadmehr Demehri
Department of Developmental Biology, Washington University School of Medicine, St Louis, Missouri, United States of America
PLoS Biol 6:e123. 2008..These observations demonstrate that local skin perturbations can drive a lethal systemic disease and have important implications for a wide range of humoral and autoimmune diseases with skin manifestations... - Canonical Notch signaling in the developing lung is required for determination of arterial smooth muscle cells and selection of Clara versus ciliated cell fateMitsuru Morimoto
Department of Developmental Biology and Division of Dermatology, Washington University School of Medicine, Box 8103, Saint Louis, MO 63110 1095, USA
J Cell Sci 123:213-24. 2010..These analyses suggest that the impact of gamma-secretase inhibitors on branching in vitro reflect a non-cell autonomous contribution from endothelial or vSMC-derived signals... - Target selectivity of vertebrate notch proteins. Collaboration between discrete domains and CSL-binding site architecture determines activation probabilityChin Tong Ong
Department of Molecular Biology and Pharmacology, Division of Dermatology, Washington University School of Medicine, St Louis, Missouri 63110, USA
J Biol Chem 281:5106-19. 2006.... - Mapping the consequence of Notch1 proteolysis in vivo with NIP-CREMarc Vooijs
Department of Molecular Biology and Pharmacology and the Department of Medicine, Division of Dermatology, Washington University Medical School, St Louis, MO 63110, USA
Development 134:535-44. 2007..These findings highlight an underappreciated layer of complexity of Notch signaling in vivo. Moreover, NIP-CRE represents a general strategy applicable for monitoring proteolysis-dependent signaling in vivo... - Physiological notch signaling maintains bone homeostasis via RBPjk and Hey upstream of NFATc1Xiaolin Tu
Department of Medicine, Washington University School of Medicine, St Louis, Missouri, United States of America
PLoS Genet 8:e1002577. 2012..Thus, Notch-RBPjk signaling functions in part through Hey1-mediated inhibition of NFATc1 to suppress osteoblastogenesis, contributing to bone homeostasis in vivo... - Notch pathway activation can replace the requirement for Wnt4 and Wnt9b in mesenchymal-to-epithelial transition of nephron stem cellsScott C Boyle
Departments of Developmental Biology and Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
Development 138:4245-54. 2011..After MET, Notch provides an instructive signal directing cells towards the proximal tubule lineage at the expense of other renal epithelial fates... - Notch signaling maintains bone marrow mesenchymal progenitors by suppressing osteoblast differentiationMatthew J Hilton
Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
Nat Med 14:306-14. 2008..Thus, mesenchymal progenitors may be expanded in vitro by activating the Notch pathway, whereas bone formation in vivo may be enhanced by transiently suppressing this pathway... - Epidermal Notch1 loss promotes skin tumorigenesis by impacting the stromal microenvironmentShadmehr Demehri
Department of Developmental Biology, Division of Dermatology, Washington University School of Medicine, Saint Louis, MO 63110 1095, USA
Cancer Cell 16:55-66. 2009.... - FGF9 and FGF20 maintain the stemness of nephron progenitors in mice and manHila Barak
Department of Developmental Biology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8103, St Louis, MO 63110, USA
Dev Cell 22:1191-207. 2012..These findings identify a long-sought-after critical component of the nephron stem cell niche and hold promise for long-term culture and utilization of these progenitors in vitro... - Notch signaling in bulge stem cells is not required for selection of hair follicle fateShadmehr Demehri
Department of Developmental Biology, Division of Dermatology, Washington University School of Medicine, Box 8103, 660 South Euclid Avenue, St Louis, MO 63110, USA
Development 136:891-6. 2009..Taken together, our findings yield detailed insight into the function of Notch signaling in hair follicle stem cells and reveal the mechanism of the replacement of Notch-deficient adult hair follicles by epidermal cysts... - Ectodomain shedding and intramembrane cleavage of mammalian Notch proteins is not regulated through oligomerizationMarc Vooijs
Department of Molecular Biology and Pharmacology, Division of Dermatology, Washington University School of Medicine, St Louis, Missouri 63110, USA
J Biol Chem 279:50864-73. 2004..Our results indicate that ligand-induced reversal of controlled TMD dimerization by the Notch extracellular domain is unlikely to underlie the regulatory mechanism of intramembranous cleavage... - Gamma-secretase composed of PS1/Pen2/Aph1a can cleave notch and amyloid precursor protein in the absence of nicastrinGuojun Zhao
Department of Developmental Biology, Washington University School of Medicine, St Louis, Missouri 63110, USA
J Neurosci 30:1648-56. 2010..This PS1/Pen2/Aph1a complex, however, is highly unstable. Thus, NCT acts to stabilize gamma-secretase but is not required for substrate recognition... - Rapid identification of homologous recombinants and determination of gene copy number with reference/query pyrosequencing (RQPS)Zhenyi Liu
Department of Developmental Biology, Washington University School of Medicine, St Louis, Missouri 63110, USA
Genome Res 19:2081-9. 2009..In addition, we also present a simple pyrosequencing-based protocol that could be used for the enrichment of homologous recombinant embryonic stem (ES) cells... - Notch1 and 2 cooperate in limb ectoderm to receive an early Jagged2 signal regulating interdigital apoptosisYonghua Pan
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, Box 8103, 660 S Euclid Avenue, St Louis, MO 63110, USA
Dev Biol 286:472-82. 2005..Thus, Notch signaling plays a non-autonomous role in digit septation... - Reduced Notch signaling leads to renal cysts and papillary microadenomasKameswaran Surendran
Department of Developmental Biology, Washington University School of Medicine, St Louis, MO 63110, USA
J Am Soc Nephrol 21:819-32. 2010.... - Genetic interplays between Msx2 and Foxn1 are required for Notch1 expression and hair shaft differentiationJing Cai
Division of Dermatology, Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
Dev Biol 326:420-30. 2009..Our results position Msx2 and Foxn1 upstream of Notch1 within the hair matrix and demonstrate that together these factors play a pivotal role in IRS, cortex and medulla differentiation... - Notch2, but not Notch1, is required for proximal fate acquisition in the mammalian nephronHui Teng Cheng
Department of Molecular Biology and Pharmacology at Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8103, St Louis, MO 63110, USA
Development 134:801-11. 2007..These results establish distinct (non-redundant), instructive roles for Notch receptors in nephron segmentation... - Molecular insights into segmentation along the proximal-distal axis of the nephronRaphael Kopan
Department of Molecular Biology, Washington University School of Medicine, St Louis, MO 63110, USA
J Am Soc Nephrol 18:2014-20. 2007..The underlying principles of regional cell signaling and transcriptional control organizing early segmentation are the subject of this review... - Notch pathway is dispensable for adipocyte specificationAmy M Nichols
Department of Molecular Biology and Pharmacology and the Department of Medicine Division of Dermatology, Washington University School of Medicine, St Louis, Missouri 63110, USA
Genesis 40:40-4. 2004..We conclude that the "canonical" Notch signaling pathway is dispensable for adipocyte specification and differentiation from either mesenchymal or epithelial progenitors... - Presenilins, Notch dose control the fate of pancreatic endocrine progenitors during a narrow developmental windowCorentin Cras-Méneur
Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St Louis, Missouri 63110, USA
Genes Dev 23:2088-101. 2009.... - Elevated epidermal thymic stromal lymphopoietin levels establish an antitumor environment in the skinShadmehr Demehri
Department of Developmental Biology and Division of Dermatology, Washington University School of Medicine, Box 8103, 660 South Euclid Avenue, St Louis, MO 63110 1095, USA Department of Internal Medicine, St Luke s Hospital, 232 South Woods Mill Road, Chesterfield, MO 63017, USA Electronic address
Cancer Cell 22:494-505. 2012..Importantly, TSLP overexpression in wild-type skin also caused resistance to tumorigenesis, confirming that TSLP functions as a tumor suppressor in the skin... - NOTCH1 regulates osteoclastogenesis directly in osteoclast precursors and indirectly via osteoblast lineage cellsShuting Bai
Departments of Pathology and Immunology, Molecular Biology and Pharmacology, and Internal Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
J Biol Chem 283:6509-18. 2008..These observations raise caution that therapeutic inhibition of NOTCH signaling may adversely accelerate bone loss in humans... - Chromatin-based mechanisms of renal epithelial differentiationKameswaran Surendran
Department of Developmental Biology, Washington University School of Medicine, 660 S Euclid Avenue, St Louis, MO 63110, USA
J Am Soc Nephrol 22:1208-12. 2011..Here we highlight some common mechanisms of cell differentiation and epigenetic regulation to discuss their implications for renal epithelial development, repair, and disease... - A requirement for Notch1 distinguishes 2 phases of definitive hematopoiesis during developmentBrandon K Hadland
Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St Louis MO 63110, USA
Blood 104:3097-105. 2004..Thus, Notch1 is required, in a cell-autonomous manner, for the establishment of long-term, definitive hematopoietic stem cells (HSCs)... - rtTA toxicity limits the usefulness of the SP-C-rtTA transgenic mouseMitsuru Morimoto
Department of Developmental Biology, Division of Dermatology, Washington University School of Medicine, Saint Louis, MO 63110, USA
Dev Biol 325:171-8. 2009..These studies demonstrate the importance of using appropriate SP-C-rtTA only controls in all experiments... - Real-time imaging of notch activation with a luciferase complementation-based reporterMa Xenia G Ilagan
Department of Developmental Biology, Washington University School of Medicine, St Louis, MO 63110, USA
Sci Signal 4:rs7. 2011..These experiments showed that Notch-LCI is an effective approach for characterizing modulators that target Notch signaling and for studying pathway dynamics in normal and disease contexts... - Analysis of transmembrane domain mutants is consistent with sequential cleavage of Notch by gamma-secretaseDilip Chandu
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, Missouri 63110, USA
J Neurochem 96:228-35. 2006..Notch (and perhaps all gamma-secretase substrates) may be cleaved by sequential proteolysis starting at S3... - The crystal structure of a partial mouse Notch-1 ankyrin domain: repeats 4 through 7 preserve an ankyrin foldOlga Y Lubman
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, Missouri 63110, USA
Protein Sci 14:1274-81. 2005..The structural preservation and stability of the C-terminal repeats shed a new light onto the mechanism of hetero-oligomeric assembly during Notch-mediated transcriptional activation... - Long-range, nonautonomous effects of activated Notch1 on tissue homeostasis in the nailMeei Hua Lin
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, MO 63110, USA
Dev Biol 263:343-59. 2003..These data support the existence of a novel, cell-nonautonomous role for Notch in maintaining homeostasis of stratified squamous epithelia by indirectly promoting mitosis in basally located cells... - A presenilin dimer at the core of the gamma-secretase enzyme: insights from parallel analysis of Notch 1 and APP proteolysisEric H Schroeter
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, MO 63110, USA
Proc Natl Acad Sci U S A 100:13075-80. 2003..We propose that gamma-secretase contains a PS dimer in its catalytic core, that binding of substrate is at a site separate from the active site, and that substrate is cleaved at the interface of two PS molecules... - Bi-compartmental communication contributes to the opposite proliferative behavior of Notch1-deficient hair follicle and epidermal keratinocytesJonghyeob Lee
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, Box 8103, 660 South Euclid Avenue, Saint Louis, MO 63110, USA
Development 134:2795-806. 2007..These results suggest that Notch1 participates in a bi-compartmental signaling network that controls homeostasis, follicular proliferation rates and melanocyte population within the skin... - Gamma-secretase activity is dispensable for mesenchyme-to-epithelium transition but required for podocyte and proximal tubule formation in developing mouse kidneyHui Teng Cheng
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, Box 8103, 660 South Euclid Avenue, St Louis, MO 63110, USA
Development 130:5031-42. 2003..These observations suggest that gamma-secretase activity, probably through activation of Notch, is required for maintaining a competent progenitor pool as well as for determining the proximal tubule and podocyte fates... 
Simple copy number determination with reference query pyrosequencing (RQPS)Zhenyi Liu
Department of Developmental Biology, School of Medicine, Washington University, St Louis, Missouri 63110, USA
Cold Spring Harb Protoc 2010:pdb.prot5491. 2010....- Notch1 loss of heterozygosity causes vascular tumors and lethal hemorrhage in miceZhenyi Liu
Department of Developmental Biology, Washington University in St Louis School of Medicine, St Louis, Missouri, USA
J Clin Invest 121:800-8. 2011..Our strategy also can be broadly applied to induce sporadic in vivo loss of heterozygosity of any conditional alleles in progenitors that experience Notch1 activation... - Genetic mosaic analysis indicates that the bulb region of coat hair follicles contains a resident population of several active multipotent epithelial lineage progenitorsRaphael Kopan
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, Missouri 63110, USA
Dev Biol 242:44-57. 2002..This latter feature resembles the behavior of hematopoietic stem cells after bone marrow transplantation, and raises the question of whether this property may be shared by stem cells in other self-renewing epithelia... - The canonical Notch signaling pathway: unfolding the activation mechanismRaphael Kopan
Department of Developmental Biology, Washington University School of Medicine, St Louis, MO 63110, USA
Cell 137:216-33. 2009..In this Review, we highlight recent studies in Notch signaling that reveal new molecular details about the regulation of ligand-mediated receptor activation, receptor proteolysis, and target selection... - Gamma-secretase: proteasome of the membrane?Raphael Kopan
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, Missouri 63110, USA
Nat Rev Mol Cell Biol 5:499-504. 2004 - A faster migrating variant masquerades as NICD when performing in vitro gamma-secretase assays with bacterially expressed Notch substratesPreston C Keller
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8231, St. Louis, Missouri 63110, USA
Biochemistry 45:5351-8. 2006.... - The role of Notch signaling in specification of podocyte and proximal tubules within the developing mouse kidneyHui Teng Cheng
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, MO 63110, USA
Kidney Int 68:1951-2. 2005.... - Moonlighting activity of presenilin in plants is independent of gamma-secretase and evolutionarily conservedAbha Khandelwal
Department of Biology, Washington University, St Louis, MO 63110, USA
Proc Natl Acad Sci U S A 104:13337-42. 2007..Introduction of PpPS into PS-deficient mouse embryonic fibroblasts rescues normal growth rates, demonstrating that at least some metazoan functions of PS are evolutionarily conserved... - Notch: a membrane-bound transcription factorRaphael Kopan
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, MO 63110, USA
J Cell Sci 115:1095-7. 2002 - AHR drives the development of gut ILC22 cells and postnatal lymphoid tissues via pathways dependent on and independent of NotchJacob S Lee
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri, USA
Nat Immunol 13:144-51. 2012..Thus, AHR was essential for ILC22 cells and postnatal intestinal lymphoid tissues. Moreover, ILC22 subsets were heterogeneous in their requirement for Notch and their effect on the generation of intestinal lymphoid tissues... - Loss of RBPj in Postnatal Excitatory Neurons Does Not Cause Neurodegeneration or Memory Impairments in Aged MiceChihiro Sato
Department of Developmental Biology, Washington University School of Medicine, St Louis, Missouri, United States of America
PLoS ONE 7:e48180. 2012..We conclude that the loss of canonical Notch signaling through the four receptors is not responsible for age-dependent neurodegeneration or learning and memory deficits seen in γ-secretase deficient mice... - The Notch ligands DLL1 and JAG2 act synergistically to regulate hair cell development in the mammalian inner earAmy E Kiernan
The Jackson Laboratory, Bar Harbor, ME 04609, USA
Development 132:4353-62. 2005..Our results demonstrate that the Notch pathway plays a dual role in regulating cellular differentiation and patterning in the cochlea, acting both through lateral inhibition and the control of cellular proliferation... - Notch activation induces apoptosis in neural progenitor cells through a p53-dependent pathwayXudong Yang
Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
Dev Biol 269:81-94. 2004..Together, these complementary gain-of-function and loss-of-function studies reveal a previously unappreciated role of Notch signaling in the regulation of apoptotic cell death during early mammalian neural development... - Notch and presenilin regulate cellular expansion and cytokine secretion but cannot instruct Th1/Th2 fate acquisitionChin Tong Ong
Department of Developmental Biology, Washington University School of Medicine, Saint Louis, Missouri, United States of America
PLoS ONE 3:e2823. 2008..The controversies surrounding the role of Notch and presenilins in Th1/Th2 polarization may reflect their role as genetic modifiers of T-helper cells differentiation... - F3/contactin acts as a functional ligand for Notch during oligodendrocyte maturationQi Dong Hu
Department of Clinical Research, Singapore General Hospital, 169608, Singapore, Singapore
Cell 115:163-75. 2003..Expression of constitutively active Notch1 or Notch2 does not upregulate MAG. Thus, F3/contactin specifically initiates a Notch/Deltex1 signaling pathway that promotes oligodendrocyte maturation and myelination... - Intramembrane proteolysis: theme and variationsMichael S Wolfe
Center for Neurologic Diseases, Harvard Medical School and Brigham and Women s Hospital, Boston, MA 02115, USA
Science 305:1119-23. 2004.... - Notch and Presenilin: regulated intramembrane proteolysis links development and degenerationDennis Selkoe
Center for Neurologic Diseases, Harvard Medical School and Brigham and Women s Hospital, Boston, MA 02115, USA
Annu Rev Neurosci 26:565-97. 2003..Elucidating the detailed mechanism of Presenilin processing of membrane proteins is important for understanding diverse signal transduction pathways and potentially for treating and preventing Alzheimer's disease... - A garden of Notch-ly delightsGerry Weinmaster
Department of Biological Chemistry, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 1737, USA
Development 133:3277-82. 2006..Hosted by the Cantoblanco Workshops on Biology and organized by Tom Gridley, José Luis de la Pompa and Juan Carlos Izpisúa Belmonte, the meeting covered diverse aspects of this important signaling pathway... - Differentiation and gene regulation: toward a holistic understanding of animal development: intercellular communication and transcriptional regulation are two sides of the same coinAlan Michelson
Curr Opin Genet Dev 12:499-502. 2002 - Quantitative dissection of the Notch:CSL interaction: insights into the Notch-mediated transcriptional switchOlga Y Lubman
T C Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, MD, USA
J Mol Biol 365:577-89. 2007..These results support an emerging molecular mechanism for the displacement of co-repressors from DNA-bound CSL by NICD... - Three-dimensional structure of the gamma-secretase complexToshihiko Ogura
Neuroscience Research Institute and Biological Information Research Center (BIRC, National Institute of Advanced Industrial Science and Technology (AIST, Umezono 1-1-4, Tsukuba, Ibaraki 305-8568, Japan
Biochem Biophys Res Commun 343:525-34. 2006..Some of the dimples in the putative transmembrane region may house the catalytic site. The large dimensions are consistent with the observation that gamma-secretase activity resides within a high molecular weight complex... - Notch1 signaling influences v2 interneuron and motor neuron development in the spinal cordXudong Yang
Center for Neurologic Diseases, Brigham and Women s Hospital, Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA
Dev Neurosci 28:102-17. 2006..These results provide support for a role of Notch1 in neuronal subtype specification in the ventral spinal cord... - Anchoring notch genetics and biochemistry; structural analysis of the ankyrin domain sheds light on existing dataOlga Y Lubman
Department of Molecular Biology and Pharmacology and the Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63104 USA
Mol Cell 13:619-26. 2004.... - Potential role of presenilin-regulated signaling pathways in sporadic neurodegenerationEdward H Koo
Department of Neurosciences, University of California, San Diego, La Jolla, California 92093, USA
Nat Med 10:S26-33. 2004..In this article, the possibility that these presenilin-regulated molecules may contribute to neurodegeneration is reviewed...