Gastrointestinal Development and Differentiation

Jadhav U, Nalapareddy K, Saxena M, O’Neill NK, Pinello L, Yuan G, Orkin SH, Shivdasani RA. Acquired Tissue-Specific Promoter Bivalency Is a Basis for PRC2 Necessity in Adult Cells. Cell 2016;  165:1389-1400 | pubmed

San Roman AK, Tovaglieri A, Breault DT, Shivdasani RA. Distinct processes and transciptional targets underlie CDX2 requirements in intestinal stem cells and differentiated villus cells. Stem Cell Reports 2015; 5:673-681 | pubmed

Sulahian R, Chen J, Arany Z, Jadhav U, Peng S, Rustgi AK, Bass AJ, Srivastava A, Hornick JL, Shivdasani RA. SOX15 governs transription in human stratified epithelia and a subset of esophageal adenocarcinomas. Cell Mol Gastroenterol Hepatol 2015; 1:598-609 | pdf | pubmed

Jayewickreme C, Shivdasani RA. Control of stomach smooth muscle development and intestinal rotation by transcription factor BARX1. Dev Biol 2015; 405:21-32 | pubmed

San Roman AK, Aronson BE, Krasinski SD, Shivdasani RA, Verzi MP. Transription factors GATA4 and HNF4A control distinct aspects of intestinal crypt and villus cells in conjunction with transcription factor CDX2. J Biol Chem 2015; 290:1850-1860 | pdf | pubmed

Morris SA, Cahan P, Li H, Zhao AM, San Roman AK, Shivdasani RA, Collins JJ, Daley GQ. Dissecting engineered cell types and enhancing cell fate conversion via CellNet. Cell 2014; 158:889-902 | pdf | pubmed

Feng R, Aihara E, Kenny S, Yang L, Li J, Varro A, Montrose MH, Shroyer NF, Wang TC, Shivdasani RA, Zavros Y. Indian hedgehog mediates gastrin-induced proliferation in stomach of adult mice. Gastroenterology 2014; | pdf | pubmed

San Roman AK, Jayewickreme CD, Murtaugh LC, Shivdasani RA. Wnt secretion from epithelial cells and subepithelial myofibroblasts is not required in the mouse intestinal stem cell niche in vivo. Stem Cell Reports 2014; 2:127-34 | pdf | pubmed

Kim TH, Li F, Ferreiro-Neira I, Ho LL, Luyten A, Nalapareddy K, Long H, Verzi M, Shivdasani RA. Broadly permissive intestinal chromatin underlies lateral inhibition and cell plasticity. Nature 2014; 506:511-5 | pdf | pubmed

Verzi MP, Shin H, San Roman A, Liu XS, Shivdasani RA. Intestinal master transcription factor CDX2 controls chromatin access for partner transcription factor binding. Mol Cell Biol 2013; 33:281-292 | pdf | pubmed

Pignon J-C, Grisanzio C, Yan G, Song J, Shivdasani RA, Signoretti S. p63-expressing cells are the stem cells of developing prostate, bladder, and colorectal epithelia. PNAS USA 2013; 110:8105-8110 | pdf | pubmed

Ho L-L, Sinha A, Verzi M, Bernt KM, Armstrong S, Shivdasani RA. DOT1L-Mediated H3K79 methylation in chromatic is dispensible for Wnt pathway-specific and other intestinal epithelial functions. Mol Cell Biol 2013; 33:1735-1745 | pdf | pubmed

Kim T-H, Escudero S, Shivdasani RA. Intact function of Lgr5 receptor-expressing intestinal stem cells in the absence of Paneth cells. Proc Natl Acad Sci USA 2012; 109:3932-3937 | pdf | pubmed

Woo J, Miletich I, Kim B-M, Sharpe PT, Shivdasani RA. Barx1-mediated inhibition of Wnt signalling in the mouse thoracic foregut controls tracheo-esophageal septation and epithelial differentiation.
PLoS One 2011; 6:e22493 | pdf | pubmed

Kim T-H, Kim B-M, Mao J, Rowan S, Shivdasani RA. Endodermal Hedgehog signals modulate Notch pathway activity in the developing digestive tract mesenchyme. Development 2011; 138:3225-3233 | pdf |pubmed

Verzi MP, Shin H, Ho L, Liu XS, Shivdasani RA. Essential and Redundant Functions of Caudal Family Proteins in Activating Adult Intestinal Genes. Mol Cell Biol 2011; 31:2026-2039 | pdf | pubmed

Kim T-H, Shivdasani RA. Notch signaling in stomach epithelial stem cell homeostasis. J Exp Med 2011; 208(4):677-688 | pdf | pubmed

Kim T-H, Shivdasani RA. Genetic Evidence That Intestinal Notch Functions Vary Regionally and Operate through a Common Mechanism of Math1 Repression. J Biol Chem 2011; 286(13):11427-11433 | pdf | pubmed

Kim B-M, Woo J, Kanellopoulou C, Shivdasani RA. Regulation of mouse stomach development and Barx1 expression by specific microRNAs. Development 2011; 138:1081-1086 | pdf | pubmed

Verzi MP, Shin H, He HH, Sulahian R, Meyer CA, Montgomery RK, Fleet JC, Brown M, Liu XS, Shivdasani RA. Differentiation-specific histone modifications reveal dynamic chromatin interactions and partners for the intestinal transcription factor CDX2. Dev Cell 2010; 19:713-726 | pdf | pubmed

Horst D, Gu X, Bhasin M, Yang Q, Verzi M, Lin D, Joseph M, Zhang X, Chen W, Li Y-P, Shivdasani RA, Libermann TA. Requirement of the epithelium-specific Ets transcription factor Spdef for mucous gland cell function in the gastric antrum. J Biol Chem 2010; 285(45):35047-55 |  pdf | pubmed

Verzi MP, Hatzis P, Philips J, Sulahian R, Schuijers J, Shin HG, Freed E, Brown MA, Lynch JP, Dang DT, Clevers H, Liu XS, Shivdasani RA. TCF4 and CDX2, major transcription factors for intestinal function, converge on the same cis-regulatory regions. Proc Natl Acad Sci USA 2010; 107:15151-15156.
doi: 10.1073/pnas.1003822107 | pdf | pubmed

Mao J, Kim B-M, Rajurkar M, Shivdasani RA, McMahon AP. Hedgehog signaling controls mesenchymal growth in the developing mammalian digestive tract. Development 2010; 137:1721-1729 | pdf | pubmed

Verzi MP, Stanfel MN, Moses KA, Kim B-M, Zhang Y, Schwartz RJ, Shivdasani RA, Zimmer WE. Role of the homeodomain transcription factor Bapx1 in mouse distal stomach development. Gastroenterology 2009; 136:1701-1710 | pdf | pubmed

Verzi MP, Khan AH, Ito S, Shivdasani RA. The forkhead transcription factor Foxq1 controls mucin gene expression and secretory granule biogenesis in mouse stomach surface mucous cells. Gastroenterology 2008; 135:591-600 | pdf | pubmed

Choi MY, Romer AI, Wang Y, Wu MP, Ito S, Leiter AB, Shivdasani RA. Requirement of the tissue-restricted homeodomain transcription factor Nkx6.3 in differentiation of gastrin-producing G-cells in the stomach antrum. Mol Cell Biol 2008; 28:3208-3218 | pdf | pubmed

Van Dyck F, Braem CV, Chen Z, Declercq J, Deckers R, Kim B-M, Ito S, Wu MK, Cohen DE, Dewerchin M, Derua R, Waelkens E, Fiette L, Roebroek A, Schuit F, Van de Ven WJM, Shivdasani RA. Loss of the PlagL2 transcription factor affects lacteal uptake of chylomicrons. Cell Metabolism 2007; 6:406-413 |pdf | pubmed

Kim B-M, Miletich I, Mao J, McMahon AP, Sharpe PA, Shivdasani RA. Independent functions and mechanisms for homeobox gene Barx1 in patterning mouse stomach and spleen. Development 2007; 134:3603-3613 | pdf | pubmed

Kim B-M, Mao J, Taketo MM, Shivdasani RA. Phases of canonical Wnt signaling during the development of mouse intestinal epithelium. Gastroenterology 2007; 133:529-538 | pdf | pubmed

Choi MY, Romer AI, Hu M, Lepourcelet M, Mechoor A, Yesilaltay A, Krieger M, Gray PA, Shivdasani RA. A dynamic expression survey identifies transcription factors relevant in mouse digestive tract development. Development 2006; 133(20):4119-29 | pdf | pubmed

Hu M, Shivdasani RA. Overlapping gene expression in fetal mouse intestine development and human colorectal cancers. Cancer Research 2005; 65:8715-8722 | pdf | pubmed

Kim BM, Buchner G, Miletich I, Sharpe PT, Shivdasani RA. The stomach mesenchymal transcription factor Barx1 specifies gastric epithelial identity through inhibition of transient Wnt signaling. Dev Cell 2005; 8:611-622 | pdf | pubmed

Drori S, Girnun GD, Tou L, Szwaya JD, Mueller E, Kia X, Shivdasani RA, Spiegelman B Hic-5 regulates an epithelial program mediated by PPAR-y. Genes & Development 2005; 19:362-375 | pdf | pubmed

Lepourcelet M, Tou L, Cai L, Sawada J, Lazar AF, Glickman JN, Williamson J, Everett AD, Redston M, Fox EA, Nakatani Y, Shivdasani RA. Insights into developmental mechanisms and cancers in the mammalian intestine derived from SAGE and study of the hepatoma-derived growth factor (HDGF).
Development 2005; 132:415-427 | pdf | pubmed

Tou L, Liu Q, Shivdasani RA. Regulation of mammalian epithelial differentiation and intestine development by class I histone deacetylases. Mol Cell Biol 2004; 24:3132-3139 | pdf | pubmed

Malik TH, von Stechow D, Bronson RT, Shivdasani RA. Deletion of the GATA domain of TRPS1 causes an absence of facial hair and provides new insights into bone disorder in inherited tricho-rhino-phalangeal syndromes. Mol Cell Biol 2002; 22:8592-8600 | pdf | pubmed

Shivdasani, RA. Molecular Regulation of Vertebrate Early Endoderm Development. Dev Biol 2002; 249:191-203 [Review] | pdf | pubmed

Lepourcelet M, Shivdasani RA. Characterization of a novel mammalian Groucho isoform and its role in transcriptional regulation. J Biol Chem 2002; 49:47732-47740 | pdf | pubmed

Zhang J, Rosenthal A, de Sauvage FJ, Shivdasani RA. Downregulation of hedgehog signaling is required for organogenesis of the small intestine in Xenopus. Dev Biol 2001; 229:188-202 | pdf | pubmed

Malik TH, Shoichet SA, Latham P, Kroll T, Peters LL, Shivdasani RA. Transcriptional repression and developmental functions of the atypical vertebrate GATA protein TRPS1. EMBO J 2001; 20:1715-1725 | pdf | pubmed

Shoichet SA, Malik TH, Rothman JH, Shivdasani RA. Action of the C. elegans GATA factor END-1 in Xenopus suggests that similar mechanisms initiate endoderm development in ecdysozoa and vertebrates. Proc Natl Acad Sci USA 2000; 97:4076-4081 | pdf | pubmed

Malik TH, Shivdasani RA. Structure and expression of a novel Frizzled gene isolated from the developing mouse gut. Biochem J 2000; 349:829-834 | pubmed

Lee YJ, Swencki B, Shoichet S, Shivdasani RA. A possible role for the High Mobility Group-box transcription factor Tcf-4 in vertebrate gut epithelial cell differentiation. J Biol Chem 1999; 274:1566-1572 | pdf | pubmed

Molecular Cancer Therapeutics

Pomerantz MM, Li F, Takeda DY, Lenci R, Chonkar A, Chabot M, Cejas P, Vazquez F, Cook J, Shivdasani RA, Bowden M, Lis R, Hahn WC1,4, Kantoff PW1, Brown M, Loda M, Long HW, Freedman ML. The androgen receptor cistrome is extensively reprogrammed in human prostate tumorgenesis. Nat Genet 2015; 47:1346-1351 | pubmed

Sulahian R, Casey F, Shen J, Qian ZR, Shin H, Ogino S, Weir BA, Vazquez F, Liu XS, Hahn WC, Bass AJ, Chan V, Shivdasani RA. An integrative analysis reveals functional targets of GATA6 transcriptional regulation in gastric cancer. Oncogene 2014; 33:5637-5648 | pdf | pubmed

Francis J, Kiezun A, Ramos AH, Serra S, Pedamallu CS, Qian ZR, Banck MS, Kanwar R, Kulkarni AA, Karpathikis A, Manzo V, Contractor T, Philips J, Nickerson R, Pho N, Hooshmand SM, Brais LK, Lawrence M, Pugh T, McKenna A, Sivachenko A, Cibulskis K, Carter SL, Ojesina AI, Freeman S, Jones RT, Voet D, Saksena G, Auclair D, Onofrio R, Shefler E, Sougnez C, Grimsby J, Green L, Lennon N, Meyer T, Caplin M, Chung DC, Beutler AS, Ogino S, Thirlwell C, Shivdasani RA, Asa SL, Harris CR, Getz G, Kulke MH, Meyerson M. Somatic mutation of CDKN1B in small intestine neuroendocrine tumors. Nat Genet 2013; 45:1483-1486 | pdf | pubmed

Horst D, Chen J, Morikawa T, Ogino S, Kirchner T, Shivdasani RA. Differential WNT activity in colorectal cancer confers limited tumorigenic potential and is regulated by MAPK signaling. Cancer Res 2012; 72:1547-1556 | pdf | pubmed

Souglakos J, Philips J, Wang R, Marwah S, Silver M, Tzardi M, Silver J, Ogino S, Hooshmand S, Kwak E, Freed E, Meyerhardt JA, Saridaki Z, Georgoulias V, Finkelstein D, Fuchs CS, Kulke MH, Shivdasani RA. Prognostic and predictive value of common mutations for treatment response and survival in patients with metastatic colorectal cancer. Br J Cancer 2009; 101:465-472 | pdf | pubmed

Firestein R, Bass AJ, Kim S-Y, Dunn IF, Silver SJ, Guney I, Freed E, Ligon AH, Vena N, Ogino S, Chheda MG, Tamayo P, Finn S, Shrestha Y, Boehm JS, Jain S, Bojarski E, Mermel C, Barretina J, Chan JA, Baselga J, Tabernero J, Root DE, Fuchs CS, Loda M, Shivdasani RA, Meyerson M, Hahn WC. CDK8 is a colorectal cancer oncogene that regulates ß-catenin signaling. Nature 2008; 455:547-551 | pdf | pubmed

Kulke MH, Freed E, Chiang D, Philips J, Zahrieh D, Glickman JN, Shivdasani RA. High-resolution analysis of genetic alterations in small bowel carcinoid tumors reveals areas of recurrent amplification and loss. Genes Chromosomes Cancer 2008; 47:591-603 | pubmed

Lepourcelet M, Chen YP, Frances DS, Wang H, Crews P, Petersen F, Bruseo C, Wood AW, Shivdasani RA. Small molecule antagonists of the oncogenic beta-cetenin/Tcf protein complex. Cancer Cell 2004; 5:91-102 | pdf | pubmed

Livingston DM, Shivdasani RA. Toward mechanism-based cancer care. JAMA 2001; 285:588-593 [Review] | pubmed

Poy F, Lepourcelet M, Shivdasani RA, Eck MJ. Structure of a human Tcf4/b-catenin complex. Nature Struct Biol 2001; 8:1053-1057 | pdf | pubmed

Megakaryocytes and Platelets

Echtler K, Stark K, Lorenz M, Kerstan S, Walch A, Jennen L, Rudelius M, Seidl S, Kremmer E, Emambokus NR, von Bruehl M-L, Frampton J, Isermann B, Genzel-Boroviczény O, Schreiber C, Mehilli J, Kastrati A, Schwaiger M, Shivdasani RA, Massberg S. Platelets contribute to postnatal occlusion of the ductus arteriosus. Nature Medicine 2010; 16:75-82 | pdf | pubmed

Kunert S, Meyer I, Fleischhauer S, Wannack M, Fiedler J, Shivdasani RA, Schulze H. The microtubule modulator RanBP10 plays a critical role in regulation of platelet discoid shape and degranulation. Blood 2009; 114:5532-5540 | pdf | pubmed

Schulze H, Dose M, Korpal M, Meyer I, Italiano JE Jr, Shivdasani RA. RanBP10 is a cytoplasmic guanine nucleotide-exchange factor that modulates non-centrosomal microtubules. J Biol Chem 2008; 283:14109-14119 | pdf | pubmed

Patel-Hett S, Richardson JL, Schulze H, Drabek K, Isaac NA, Hoffmeister K, Shivdasani RA, Bulinski JC, Galjart N, Hartwig JH, Italiano JE Jr. Visualization of microtubule growth in living platelets reveals a dynamic marginal band with multiple microtubules. Blood 2008; 111:4605-4616 | pdf | pubmed

Junt T, Schulze H, Chen Z, Massberg S, Goerge T, Krueger A, Richardson J, Wagner DD, Graf T, Italiano JE, Shivdasani RA, von Andrian UH. Dynamic visualization of thrombopoiesis within bone marrow. Science 2007; 317:1767-1770 | pubmed

Chen Z, Naveiras O, Balduini A, Mammoto A, Conti MA, Adelstein RS, Ingber D, Daley GQ, Shivdasani RA. The May-Hegglin anomaly gene Myh9 is a negative regulator of platelet biogenesis modulated by the Rho-ROCK pathway. Blood 2007; 110:171-179 | pdf | pubmed

Chen Z, Hu M, Shivdasani RA. Expression analysis of primary mouse megakaryocyte differentiation and its application to identify stage-specific molecular markers and a novel transcriptional target of NF-E2. Blood 2007; 109:1451-1459 | pdf | pubmed

Schulze H, Korpal M, Hurov J, Kim S-W, Zhang J, Cantley LC, Graf T, Shivdasani RA. Characterization of the megakaryocyte demarcation membrane system and its role in thrombopoiesis. Blood 2006; 107:3868-3875 | pdf | pubmed

Richardson J, Shivdasani RA, Boers C, Hartwig JH, Italiano JE Jr. Mechanisms of organelle transport and capture along proplatelets during platelet production. Blood 2005; 106:4066-4075 | pdf | pubmed

Patel SR, Richardson J, Schulze H, Kahle E, Galjart N, Drabek K, Shivdasani RA, Hartwig JH, Italiano JE Jr. Differential roles of microtubule assembly and sliding in proplatelet formation by megakaryocytes. Blood 2005; 106:4076-4085 | pdf | pubmed

Schulze H, Korpal M, Bergmeier W, Italiano JE, Wahl SM, Shivdasani RA. Interactions between the megakaryocyte/platelet-specific beta-1 tubulin and the secretory leukocyte protease inhibitor SLPI suggest a role for regulated proteolysis in platelet functions. Blood, 2004; 104: 3949-3957 | pdf | pubmed

Tiwari S, Italiano JE, Barral DC, Mules EH, Novak EK, Swank RT, Seabra MC, Shivdasani RA. A role for Rab27b in NF-E2-dependent pathways of platelet formation. Blood, 2003; 102:3970-3979 | pdf | pubmed

Italiano JE, Bergmeier W, Tiwari S, Falet H, Hartwig JH, Hoffmeister K, Andre P, Wagner DD, Shivdasani RA. Mechanisms and implications of platelet discoid shape. Blood 2003; 101:4789-4796 | pdf | pubmed

Italiano JE, Shivdasani RA. Megakaryocytes and beyond: the birth of platelets. J Thromb Haemost, 2003; 1:1174-1181 | pubmed

Shivdasani RA. Molecular and transcriptional regulation of megakaryocyte differentiation. Stem Cells 2001; 19:397-407 [Review] | pdf | pubmed

Schwer HD, Lecine P, Tiwari S, Italiano JE, Hartwig JH, Shivdasani RA. A lineage-restricted and divergent beta-tubulin isoform is essential for the biogenesis, structure and function of blood platelets. Curr Biol 2001; 11:579-586 | pdf | pubmed

Lecine P, Italiano JE, Kim SW, Villeval J-L, Shivdasani RA. Hematopoietic-specific beta1 tubulin participates in a pathway of platelet biogenesis dependent on the transcription factor NF-E2. Blood 2000; 96:1366-1373 | pdf | pubmed

Vyas P, Ault K, Jackson CW, Orkin SH, Shivdasani RA. Consequences of GATA-1 deficiency in megakaryocytes and platelets. Blood 1999; 93:2867-2875 | pdf | pubmed

Levin J, Peng J-P, Baker GR, Villeval J-L, Lecine P, Burstein SA, Shivdasani RA. Pathophysiology of thrombocytopenia and anemia in mice lacking transcription factor NF-E2. Blood 1999; 94: 3037-3047 | pdf | pubmed

Italiano JE, Lecine P, Shivdasani RA, Hartwig JH. Blood platelets are assembled principally at the ends of proplatelet processes produced by differentiated megakaryocytes. J Cell Biol 1999; 147:1299-1312 | pdf | pubmed

de Sauvage FJ, Villeval J-L, Shivdasani RA. Regulation of megakaryocytopoiesis and platelet production: Lessons from animal models. J Lab Clin Med 1998; 131:496-501 [Review] | pubmed

Lecine P, Blank V, Shivdasani RA. Characterization of the hematopoietic transcription factor NF-E2 in primary murine megakaryocytes. J Biol Chem 1998; 273:7572-7578 | pdf | pubmed

Lecine P, Villeval J-L, Vyas P, Swencki B, Xu Y, Shivdasani RA. Mice lacking transcription factor NF-E2 provide in vivo validation of the proplatelet model of thrombocytopoiesis and show a platelet production defect that is intrinsic to megakaryocytes. Blood 1998; 92:1609-1616 | pdf | pubmed

Shivdasani RA, Fujiwara Y, McDevitt MA, Orkin SH. A lineage-selective knockout establishes the critical role of transcription factor GATA-1 in megakaryocyte growth and platelet development. EMBO J 1997; 16:3965-3973 | pdf | pubmed

Shivdasani RA, Fielder P, Keller G-A, Orkin SH, de Sauvage FJ. Regulation of the serum concentra-tion of thrombopoietin in thrombocytopenic NF-E2 knockout mice. Blood 1997; 90:1821-1827 | pdf | pubmed

Shivdasani RA, Rosenblatt MF, Zucker-Franklin D, Jackson CW, Hunt P, Saris CJM, Orkin SH. Transcription factor NF-E2 is required for platelet formation independent of the actions of thrombopoietin/MGDF in megakaryocyte development. Cell 1995; 81:695-704 | pdf | pubmed

Developmental Hematopoiesis

Luyten A, Zang C, Liu XS, Shivdasani RA. Active enhancers are delineated de novo during hematopoiesis, with limited lineage fidelity among specified primary blood cells.  Genes Dev 2014; 28:1827-1839 | pdf | pubmed

Schulze H, Korpal M, Hurov J, Kim S-W, Zhang J, Cantley LC, Graf T, Shivdasani RA. Characterization of the megakaryocyte demarcation membrane system and its role in thrombopoiesis. Blood 2006; 107:3868-3875 | pdf | pubmed

Kacena MA, Shivdasani RA, Wilson K, Xi Y, Troiano N, Nazarian A, Gundberg CM, Bouxsein ML, Lorenzo JA, Horowitz MC. Megakaryocyte-osteoblast interaction revealed in mice deficient in transcription factors GATA-1 and NF-E2. J Bone Miner Res 2004; 19:652-660 | pdf | pubmed

McDevitt MA, Fujiwara Y, Shivdasani RA, Orkin SH. An upstream, DNaseI hypersensitive region of the hematopoietic-expressed transcription factor GATA-1 gene confers developmental specificity in transgenic mice. Proc Natl Acad Sci USA 1997; 94:7976-7981 | pdf | pubmed

Shivdasani RA, Orkin SH. The transcriptional control of hematopoiesis. Blood 1996; 87:4025-4039 [Review] | pdf | pubmed

Peters LL, Shivdasani RA, Liu SC, Hanspal M, John KM, Gonzalez JM, Brugnara C, Gwynn B, Mohandas N, Alper SL, Orkin SH, Lux SE. Anion exchanger 1 (Band 3) is required to prevent erythrocyte membrane surface loss but not to form the membrane skeleton. Cell 1996; 86:917-927 | pdf | pubmed

Shivdasani RA, Mayer EL, Orkin SH. Absence of blood formation in mice lacking the T-cell leukaemia oncoprotein Tal-1/SCL. Nature 1995; 373:432-434 | pubmed

Shivdasani RA, Orkin SH. Erythropoiesis and globin gene expression in mice lacking the transcription factor NF-E2. Proc Natl Acad Sci USA 1995; 92:8690-8694 | pdf | pubmed