Publications

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Liu, Z., Brunskill, E., Boyle, S., Chen, S., Turkoz, M., Guo, Y., Grant, R., Kopan, R. Second-generation Notch1 activity-trap mouse line (N1IP::CreHI) provides a more comprehensive map of cells experiencing Notch1 activity. Development. 2015 Mar 15;142(6):1193-202.

Liu Z, Brunskill E, Varnum-Finney B, Zhang C, Zhang A, Jay PY, Bernstein I, Morimoto M, Kopan R. The intracellular domains of Notch1 and 2 are functionally equivalent during development and carcinogenesis. Development. 2015 Jul 15;142(14):2452-63.

Demitrack ES, Gifford GB, Keeley TM, Carulli AJ, VanDussen KL, Thomas D, Giordano TJ, Liu Z, Kopan R, Samuelson LC. Read Notch signaling regulates gastric antral LGR5 stem cell function.. EMBO J. 2015 Oct 14;34(20):2522-36.

Hass MR, Liow HH, Chen X, Sharma A, Inoue YU, Inoue T, Reeb A, Martens A, Fulbright M, Raju S, Stevens M, Boyle S, Park JS, Weirauch MT, Brent MR, Kopan R. SpDamID: Marking DNA Bound by Protein Complexes Identifies Notch-Dimer Responsive Enhancers. Molecular Cell. 2015 Aug 20;59(4):685-97.

Chen S, Brunskill EW, Potter SS, Dexheimer PJ, Salomonis N, Aronow BJ, Hong CI, Zhang T, Kopan R. Intrinsic Age-Dependent Changes and Cell-Cell Contacts Regulate Nephron Progenitor Lifespan. Developmental Cell. 2015 Oct 12;35(1):49-62.

Gama-Norton L, Ferrando E, Ruiz-Herguido C, Liu Z, Guiu J, Islam AB, Lee SU, Yan M, Guidos CJ, López-Bigas N, Maeda T, Espinosa L, Kopan R, Bigas A. Notch signal strength controls cell fate in the haemogenic endothelium. Nat Commun. 2015 Oct 14;6:8510. 

Boyle, S.C., Liu, Z., and Kopan, RNotch signaling is required for the formation of mesangial cells from a stromal mesenchyme precursor during kidney development. Development. 2014 Jun;44(6):851-7.

Demehri, S., Yockey, L.J., Visness, C.M., Jaffee, K.F., Turkoz, A., Wood, R.A., O'Connor, G.T., Kattan, M., Gern, J.E., Gergen, P.J., et al. Circulating TSLP associates with decreased wheezing in non-atopic preschool children: Data from the URECA birth cohort. Clin Exp Allergy. 2014 Jun;44(6):851-7. 

Kopan, R., Chen, S., Little, M. Nephron progenitor cells: shifting the balance of self-renewal and differentiation. Curr Top Dev Biol. 2014;107:293-331.

Kopan, R., Chen, S., Liu, Z. Alagille, Notch, and robustness: why duplicating systems does not ensure redundancyPediatr Nephrol. 2014 Apr;29(4):651-7.

Chillakuri, C.R., Sheppard, D., Ilagan, M.X., Holt, L.R., Abbott, F., Liang, S., Kopan, R., Handford, P.A., and Lea, S.M. Structural analysis uncovers lipid-binding properties of notch ligands. Cell Rep. 2013 Nov 27;5(4):861-7.

Zhao, Z.Q., Huo, F.Q., Jeffry, J., Hampton, L., Demehri, S., Kim, S., Liu, X.Y., Barry, D.M., Wan, L., Liu, Z.C., et al. Chronic itch development in sensory neurons requires BRAF signaling pathways. J Clin Invest. 2013 Nov 1; 123(11): 4769–4780.

Satpathy, A.T., Briseno, C.G., Lee, J.S., Ng, D., Manieri, N.A., Kc, W., Wu, X., Thomas, S.R., Lee, W.L., Turkoz, M., McDonald, K. G., Meredith, M. M., Song, C., Guidos, C. J., Newberry, R. D., Ouyang, W., Murphy, T. L., Stappenbeck, T. S., Gommerman, J. L., Nussenzweig, M. C. Colonna, M., Kopan, R., Murphy, K. M. Notch2-dependent classical dendritic cells orchestrate intestinal immunity to attaching-and-effacing bacterial pathogens. Nat Immunol. 2013. 14, 937-948.

Liu, Z., Chen, S., Boyle, S., Ilagan, M.X., Zhu, Y., Zhang, A., and Kopan, R. The Extracellular Domain of Notch2 Increases its Cell surface Abundance and Ligand Responsiveness During Kidney. Dev Cell. 2013 Jun 24;25(6):585-98.

Yockey, L.J., Demehri, S., Turkoz, M., Turkoz, A., Ahern, P.P., Jassim, O., Manivasagam, S., Kearney, J.F., Gordon, J.I., and Kopan, R. The absence of a microbiota enhances TSLP expression in mice with defective skin barrier but does not affect the severity of their allergic inflammation. Journal Invest Dermatology. 2013 Dec;133(12):2714-21.

Liu, Z., Liu, Z., Walters, B. J., Owen, T., Kopan, R., and Zuo, J. In vivo visualization of notch1 proteolysis reveals the heterogeneity of notch1 signaling activity in the mouse cochlea. PLoS One. 2013 May 31;8(5):e64903.

Groot AJ, Cobzaru C, Weber S, Saftig P, Blobel CP, Kopan R, Vooijs M, Franzke CW. Epidermal ADAM17 Is Dispensable for Notch Activation. J Invest Dermatol. 2013 Sep;133(9):2286-8.

*Barak, H., Huh, S.-H., Chen, S., Jeanpierre, C., Martinovic, J., Parisot, M., Bole-Feysot, C., Nitschké, P., Salomon, R., Antignac, C., Ornitz, D. and Kopan R.FGF9 and FGF20 maintain the stemness of nephron progenitors in mice and man. Developmental Cell. 2012 Jun 12;22(6):1191-207.

Tu, X., Chen, J., Lim, J., Karner, C.M., Lee, S.Y., Heisig, J., Wiese, C., Surendran, K., Kopan, R., Gessler, M., et al. Physiological Notch Signaling Maintains Bone Homeostasis via RBPjk and Hey Upstream of NFATc1. PLoS Genet. 2012;8(3):e1002577.

Zheng J, Watanabe H, Wines-Samuelson M, Zhao H, Gridley T, Kopan R, Shen J. Conditional Deletion of Notch1 and Notch2 Genes in Excitatory Neurons of Postnatal Forebrain Does Not Cause Neurodegeneration or Reduction of Notch mRNAs and Proteins. JBC. 2012 Jun 8;287(24):20356-68.

Demehri, S., Turkoz, A., Manivasagam, S., Yockey, L.J., Turkoz, M., and Kopan, R.Elevated Epidermal Thymic Stromal Lymphopoietin Levels Establish An Anti-Tumor Environment In The Skin. Cancer Cell. 2012 Oct 16;22(4):494-505.

Sato C, Turkoz M, Dearborn JT, Wozniak DF, Kopan R, Hass MR. Loss of RBPj in Postnatal Excitatory Neurons Does Not Cause Neurodegeneration or Memory Impairments in Aged Mice. PLoS One. 2012;7(10):e48180.

Morimoto, M., Nishinakamura, R., Saga, Y., and Kopan, R.Different assemblies of Notch receptors coordinate the distribution of the major bronchial Clara, ciliated and neuroendocrine cells. Development. 2012 Dec 1;139(23):4365-73.

Liu Z, Turkoz A, Jackson EN, Corbo JC, Engelbach JA, Garbow JR, Piwnica-Worms DR and Kopan R. Notch1 loss-of-heterozygosity causes vascular tumors in mice. J Clin Invest. 2011 Feb;121(2):800-8.

Pellegrinet, L., V. Rodilla, Z. Liu, S. Chen, U. Koch, L. Espinosa, K.H. Kaestner, R. Kopan, J. Lewis, and F. Radtke. Dll1- and Dll4-mediated Notch signaling is required for homeostasis of intestinal stem cells. Gastroenterology. 2011 Apr;140(4):1230-1240.e1-7.

Ilagan, M. X., Sora, L., Fulbright, M., Piwnica-Worms, D. and Kopan, R.Real-time imaging of Notch activation using a Luciferase Complementation-based Reporter. Science Signaling. 2011 Jul 12;4(181):rs7.

Boyle SC, Kim M, Valerius MT, McMahon AP, Kopan R. Notch pathway activation can replace the requirement for Wnt4 and Wnt9b in mesenchymal-to-epithelial transition of nephron stem cells. Development. 2011 Oct;138(19):4245-54.

Lee, J.S., Cella, M., McDonald, K.G., Garlanda, C., Kennedy, G.D., Nukaya, M., Mantovani, A., Kopan, R., Bradfield, C.A., Newberry, R.D., et al. AHR drives the development of gut ILC22 cells and postnatal lymphoid tissues via pathways dependent on and independent of Notch. Nat Immunol. 2011 Nov 20;13(2):144-51.

*Surendran K, Boyle S, Barak H, Kim M, Stromberski C, McCright B and Kopan R. 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 dosageDev Biol. 2010 Jan 15;337(2):386-95.

Morimoto M, Liu Z, Cheng HT, Winters N, Bader D and Kopan R. Canonical Notch signaling in the developing lung is required for determination of arterial smooth muscle cells and selection of Clara versus ciliated cell fateJ Cell Sci. 2010 Jan 15;123(Pt 2):213-24.

Roe CM, Fitzpatrick AL, Xiong C, Sieh W, Kuller L, Mller JP, Williams MM, Kopan R, Behrens MI and Moris JC. Cancer linked to Alzheimer disease but not vascular dementia. Neurology. 2010 Jan 12;74(2):106-12.

Zhao G, Liu Z, Ilagan MX and Kopan R. y-Secretase composed of PS1/Pen2/Aph1a can cleave Notch and amyloid precursor protein in the absence of nicastrin. J Neurosci. 2010 Feb 3;30(5):1648-56.

Johnson SE, Ilagan MX, Kopan R and Barrick D: Thermodynamic analysis of the CSL:Notch interaction: Distribution of binding energy of the Notch RAM region to the CSL beta-trefoil domain and the mode of competition with the viral transactivator EBNA2. J Biol Chem. 2010 Feb 26;285(9):6681-92.

Dumortier A, Durham A-D, Di Piazza M, Vauclair S, Koch U, Ferrand G, Ferrero I, Demehri S, Song LL, Farr AG, Leonard WJ, Kopan R, Miele L, Hohl D, Finke D and Radtke F. Atopic dermatitis-like disease and associated lethal myeloproliferative disorder arise from loss of Notch signaling in the murine skin. PLoS ONE. 2010 Feb 18;5(2):e9258.

Surendran K, Selassie M, Liapis H, Krigman H and Kopan R. Reduced Notch signaling leads to renal cysts and papillary microadenomas. J Am Soc Nephrol. 2010 May;21(5):819-32.

Tong Y, Yamaguchi H, Giaime E, Boyle S, Kopan R, Kelleher RJ 3rd and Shen J. Loss of leucine-rich repeat kinase 2 causes impairment of protein degradation pathways, accumulation of a-synuclein, and apoptotic cell death in aged mice. Proc Natl Acad Sci USA. 2010 May 25;107(21):9879-84.

Liu Z, Schneider DL, Kornfeld K and Kopan R. Simple copy number determination with reference query pyrosequencing (RQPS). Cold Spring Harb Protoc. 2010 Sep 1;2010(9):pdb.prot5491.

Arnett KL, Hass M, McArthur DG, Ilagan MX, Aster JC and Kopan, R: Structural and mechanistic insights into cooperative assembly of dimeric Notch transcription complexes. Nat Struct Mol Biol. 2010 Nov;17(11):1312-7.

Morimoto M and Kopan R. rtTA toxicity limits the usefulness of the SP-C-rtTA transgenic mouse. Developmental Biology. 2009 325:171-178.

Cai J, Lee J, Kopan R and Ma L. Genetic interplays between Msx2 and Foxn1 are required for Notch1 expression and hair shaft differentiationDevelopmental Biology. 2009 326:420-430.

Demehri S and Kopan R. Notch signaling in bulge stem cells is not required for selection of hair follicle fate. Development. 2009 136:891-896.

Demehri S, Morimoto M, Holtzman MJ and Kopan R. Skin-derived TSLP triggers progression from epidermal-barrier defects to asthma. PLoS Biol. 2009 7(5): e1000067.

Demehri S, Turkoz A and Kopan R. Epidermal Notch1 loss promotes skin tumorigenesis by impacting the stromal microenvironmentCancer Cell. 2009 16:55-66.

Bazzi H, Demehri S, Potter CS, Barber AG, Awgulewitsch A, Kopan R and Christiano AM: Desmoglein 4 is regulated by transcription factors implicated in hair shaft differentiation. Differentiation. 2009. 2009 Dec;78(5):292-300.

Cras-Meneur C, Li L, Kopan R and Permutt MA: Presenilins, Notch dose control the fate of pancreatic endocrine progenitors during a narrow developmental window. Genes Dev. 2009. 23:2088-2101.

van Tetering G, van Diest P, Verlaan I, van der Wall E, Kopan R and Vooijs M: The metalloprotease ADAM10 is required for notch1 S2 cleavage. J Biol Chem. 2009. 284:31018-31027.

Liu Z, Obenauf AC, Speicher MR and Kopan R: Rapid identification of homologous recombinants and determination of gene copy number with reference/query pyrosequencing (RQPS). Genome Res. 2009 19:2081-2089.

Riesenberg AN, Liu Z, Kopan R and Brown NL. Rbpj cell autonomous regulation of retinal ganglion cell and cone photoreceptor fates in the mouse retina. J Neurosci. 2009. 29:12865-12877.

Bai S, Kopan R, Zou W, Hilton MJ, Ong CT, Long F, Ross FP and Teitelbaum SL. Notch1 regulates osteoclastogenesis directly in osteoclast precursors and indirectly via osteoblast lineage cells. J Biol Chem. 2008 283:6509-6518.

Lee J, Wu W and Kopan R. Murine vibrissae cultured in serum-free medium reinitiate anagen. J Invest Dermatol. 2008 128:482-485.

Hilton MJ, Tu X, Wu X, Bai S, Zhao H, Kobayashi T, Kronenberg HM, Teitelbaum SL, Ross FP, Kopan R and Long F. Notch signaling maintains bone marrow mesenchymal progenitors by suppressing osteoblast differentiation. Nature Med. 2008 14:306-314.

Demehri S, Liu Z, Lee J, Lin MH, Crosby SD, Roberts CJ, Grigsby PW, Miner JH, Farr AG and Kopan R. Notch-deficient skin induces a lethal systemic B-lymphoproliferative disorder by secreting TSLP, a sentinel for epidermal integrity. PLoS Biol. 2008 6:e123.

Ong CT, Sedy JR, Murphy KM and Kopan R. Notch and presenilin regulate cellular expansion and cytokine secretion but cannot instruct Th1/Th2 fate acquisitionPLoS ONE. 2008. 3:e2823.

Kopan R, Nye J and Weintraub H. The intracellular domain of mouse Notch: a constitutively activated repressor of myogenesis directed at the basic helix-loop-helix region of MyoD. Development. 1994 120:2385-2396.

Kopan R, Schroeter E, Weintraub H and Nye JS. Signal transduction by activated mNotch: Importance of proteolytic processing and its regulation by the extracellular domain. Proc Natl Acad Sci USA. 1996 93:1683-1688.

Schroeter EH, Kisslinger JA and Kopan R. Notch 1 signaling requires ligand-induced proteolytic release of intracellular domain. Nature. 1998 393:382-386.

De Strooper B, Annaert W, Cupers P, Saftig P, Craessaerts K, Mumm JS, Schroeter EH, Schrijvers V, Wolfe MS, Ray WJ, Goate A and Kopan R. A Presenilin-1-dependent, g-secretase-like protease mediates release of Notch intracellular domain. Nature. 1999 398:518-522.

Mumm JS, Schroeter EH, Saxena MT, Griesemer A, Tian X, Pan DJ, Ray WJ and Kopan R. A ligand-induced extracellular cleavage regulates g-secretase-like proteolytic activation of Notch 1. Mol Cell. 2000 5:197-206.

*Huppert S, Le A, Schroeter EH, Mumm JS, Saxena MT, Milner L and Kopan REmbryonic lethality in mice homozygous for a processing-deficient allele of Notch1. Nature. 2000 405:966-970.

Hadland BK, Huppert S, Kanungo J, Xue Y, Jiang R, Gridley T, Conlon R, Cheng AM, Kopan R** and Longmore GD. A requirement for Notch1 distinguishes two phases of definitive hematopoiesis during development. Blood. 2004 104:3097-3105.

*Pan Y, Lin MH, Tian X, Cheng HT, Gridley T, Shen J and Kopan R. Gamma-secretase functions through Notch signaling to maintain skin appendages but is not required for their patterning or initial morphogenesis. Dev Cell. 2004 7:731–743.

Cheng HT and Kopan RThe role of Notch signaling in specification of podocyte and proximal tubules within the developing mouse kidney. Kidney Int. 2005 68:1951-1952.

*Cheng HT, Kim M, Valerius MT, Surendran K, Schuster-Gossler K, Gossler A, McMahon AP and Kopan R. Notch2, but not Notch1, is required for proximal fate acquisition in the mammalian nephron. Development. 2007 134:801-811.

Contact Us

A photo of Raphael Kopan.

Raphael Kopan, PhD
William K. Schubert Professor of Pediatrics, University of Cincinnati College of Medicine

Director of the Division of Developmental Biology, Cincinnati Children's Hospital Medical Center

Mailing Address:
3333 Burnet Avenue, MLC 7029
Cincinnati, OH 45229-3039

Phone: 513-636-2090
Fax: 513-636-4317
Email: raphael.kopan@cchmc.org