Photo of Ramesh A. Shivdasani,  MD, PhD

Ramesh A. Shivdasani, MD, PhD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute

Ramesh A. Shivdasani, MD, PhD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Professor, Medicine, Harvard Medical School
  • Professor of Medicine, Medical Oncology, Dana-Farber Cancer Institute

DF/HCC PROGRAM AFFILIATION

DF/HCC ASSOCIATIONS

  • Member, Center Scientific Council

Research Abstract

Transcriptional, signaling, and chromatin regulation of embryonic and adult stomach and intestine development and differentiation.

Publications

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  • Jayewickreme CD, Shivdasani RA. Control of stomach smooth muscle development and intestinal rotation by transcription factor BARX1. Dev Biol 2015. PubMed
  • Schumacher MA, Aihara E, Feng R, Engevik A, Shroyer NF, Ottemann KM, Worrell RT, Montrose MH, Shivdasani RA, Zavros Y. The use of murine-derived fundic organoids in studies of gastric physiology. J Physiol 2015. PubMed
  • San Roman AK, Aronson BE, Krasinski SD, Shivdasani RA, Verzi MP. Transcription factors GATA4 and HNF4A control distinct aspects of intestinal homeostasis in conjunction with transcription factor CDX2. J Biol Chem 2015; 290:1850-60. 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. PubMed
  • 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; 28:1827-39. 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. 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. 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. PubMed
  • Shivdasani RA. Radiation redux: reserve intestinal stem cells miss the call to duty. Cell Stem Cell 2014; 14:135-6. PubMed
  • Francis JM, Kiezun A, Ramos AH, Serra S, Pedamallu CS, Qian ZR, Banck MS, Kanwar R, Kulkarni AA, Karpathakis A, Manzo V, Contractor T, Philips J, Nickerson E, Pho N, Hooshmand SM, Brais LK, Lawrence MS, 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 R, Asa SL, Harris CR, Getz G, Kulke M, Meyerson M. Somatic mutation of CDKN1B in small intestine neuroendocrine tumors. Nat Genet 2013; 45:1483-6. PubMed
  • Pignon JC, Grisanzio C, Geng Y, Song J, Shivdasani RA, Signoretti S. p63-expressing cells are the stem cells of developing prostate, bladder, and colorectal epithelia. Proc Natl Acad Sci U S A 2013. PubMed
  • Ho LL, Sinha A, Verzi M, Bernt KM, Armstrong SA, Shivdasani RA. DOT1L-mediated H3K79 methylation in chromatin is dispensable for Wnt pathway-specific and other intestinal epithelial functions. Mol Cell Biol 2013; 33:1735-45. PubMed
  • Verzi MP, Shin H, San Roman AK, Liu XS, Shivdasani RA. Intestinal master transcription factor CDX2 controls chromatin access for partner transcription factor binding. Mol Cell Biol 2012. PubMed
  • Dulak AM, Schumacher SE, van Lieshout J, Imamura Y, Fox C, Shim B, Ramos AH, Saksena G, Baca SC, Baselga J, Tabernero J, Barretina J, Enzinger PC, Corso G, Roviello F, Lin L, Bandla S, Luketich JD, Pennathur A, Meyerson M, Ogino S, Shivdasani RA, Beer DG, Godfrey TE, Beroukhim R, Bass AJ. Gastrointestinal adenocarcinomas of the esophagus, stomach, and colon exhibit distinct patterns of genome instability and oncogenesis. Cancer Res 2012; 72:4383-93. PubMed
  • Takada K, Zhu D, Bird GH, Sukhdeo K, Zhao JJ, Mani M, Lemieux M, Carrasco DE, Ryan J, Horst D, Fulciniti M, Munshi NC, Xu W, Kung AL, Shivdasani RA, Walensky LD, Carrasco DR. Targeted disruption of the BCL9/β-catenin complex inhibits oncogenic Wnt signaling. Sci Transl Med 2012; 4:148ra117. PubMed
  • Kim TH, Shivdasani RA. Stem cell niches: famished Paneth cells, gluttonous stem cells. Curr Biol 2012; 22:R579-80. 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; 72:1547-56. PubMed
  • Kim TH, Escudero S, Shivdasani RA. Intact function of Lgr5 receptor-expressing intestinal stem cells in the absence of Paneth cells. Proc Natl Acad Sci U S A 2012; 109:3932-7. PubMed
  • Kostic AD, Gevers D, Pedamallu CS, Michaud M, Duke F, Earl AM, Ojesina AI, Jung J, Bass AJ, Tabernero J, Baselga J, Liu C, Shivdasani RA, Ogino S, Birren BW, Huttenhower C, Garrett WS, Meyerson M. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res 2012. PubMed
  • Yonesaka K, Zejnullahu K, Okamoto I, Satoh T, Cappuzzo F, Souglakos J, Ercan D, Rogers A, Roncalli M, Takeda M, Fujisaka Y, Philips J, Shimizu T, Maenishi O, Cho Y, Sun J, Destro A, Taira K, Takeda K, Okabe T, Swanson J, Itoh H, Takada M, Lifshits E, Okuno K, Engelman JA, Shivdasani RA, Nishio K, Fukuoka M, Varella-Garcia M, Nakagawa K, Jänne PA. Activation of ERBB2 signaling causes resistance to the EGFR-directed therapeutic antibody cetuximab. Sci Transl Med 2011; 3:99ra86. PubMed
  • Kim TH, Kim BM, Mao J, Rowan S, Shivdasani RA. Endodermal Hedgehog signals modulate Notch pathway activity in the developing digestive tract mesenchyme. Development 2011; 138:3225-33. PubMed
  • Verzi MP, Shin H, Ho LL, Liu XS, Shivdasani RA. Essential and redundant functions of caudal family proteins in activating adult intestinal genes. Mol Cell Biol 2011. PubMed
  • Kim TH, Shivdasani RA. Notch signaling in stomach epithelial stem cell homeostasis. J Exp Med 2011. PubMed
  • Kim TH, Shivdasani RA. Genetic evidence that intestinal Notch functions vary regionally and operate through a common mechanism of Math1 repression. J Biol Chem 2011; 286:11427-33. PubMed
  • Kim BM, Woo J, Kanellopoulou C, Shivdasani RA. Regulation of mouse stomach development and Barx1 expression by specific microRNAs. Development 2011; 138:1081-6. 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; 19:713-26. PubMed
  • Horst D, Gu X, Bhasin M, Yang Q, Verzi M, Lin D, Joseph M, Zhang X, Chen W, Li YP, Shivdasani RA, Libermann TA. Requirement of the epithelial-specific ETS transcription factor SPDEF for mucous gland cell function in the gastric antrum. J Biol Chem 2010; 285:35047-55. PubMed
  • Verzi MP, Shivdasani RA. Stem cells: The intestinal-crypt casino. Nature 2010; 467:1055-6. PubMed
  • Verzi MP, Hatzis P, Sulahian R, Philips J, Schuijers J, Shin H, Freed E, Lynch JP, Dang DT, Brown M, 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 U S A 2010; 107:15157-62. PubMed
  • Mao J, Kim BM, Rajurkar M, Shivdasani RA, McMahon AP. Hedgehog signaling controls mesenchymal growth in the developing mammalian digestive tract. Development 2010; 137:1721-9. PubMed
  • Echtler K, Stark K, Lorenz M, Kerstan S, Walch A, Jennen L, Rudelius M, Seidl S, Kremmer E, Emambokus NR, von Bruehl ML, 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. Nat Med 2010; 16:75-82. 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; 114:5532-40. PubMed
  • Bass AJ, Watanabe H, Mermel CH, Yu S, Perner S, Verhaak RG, Kim SY, Wardwell L, Tamayo P, Gat-Viks I, Ramos AH, Woo MS, Weir BA, Getz G, Beroukhim R, O'Kelly M, Dutt A, Rozenblatt-Rosen O, Dziunycz P, Komisarof J, Chirieac LR, Lafargue CJ, Scheble V, Wilbertz T, Ma C, Rao S, Nakagawa H, Stairs DB, Lin L, Giordano TJ, Wagner P, Minna JD, Gazdar AF, Zhu CQ, Brose MS, Cecconello I, Jr UR, Marie SK, Dahl O, Shivdasani RA, Tsao MS, Rubin MA, Wong KK, Regev A, Hahn WC, Beer DG, Rustgi AK, Meyerson M. SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas. Nat Genet 2009; 41:1238-42. 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; 101:465-72. PubMed
  • Pomerantz MM, Ahmadiyeh N, Jia L, Herman P, Verzi MP, Doddapaneni H, Beckwith CA, Chan JA, Hills A, Davis M, Yao K, Kehoe SM, Lenz HJ, Haiman CA, Yan C, Henderson BE, Frenkel B, Barretina J, Bass A, Tabernero J, Baselga J, Regan MM, Manak JR, Shivdasani R, Coetzee GA, Freedman ML. The 8q24 cancer risk variant rs6983267 shows long-range interaction with MYC in colorectal cancer. Nat Genet 2009; 41:882-4. PubMed
  • Baba Y, Nosho K, Shima K, Freed E, Irahara N, Philips J, Meyerhardt JA, Hornick JL, Shivdasani RA, Fuchs CS, Ogino S. Relationship of CDX2 loss with molecular features and prognosis in colorectal cancer. Clin Cancer Res 2009; 15:4665-73. PubMed
  • Montgomery RK,Shivdasani RA. Prominin1 (CD133) as an Intestinal Stem Cell Marker: Promise and Nuance. Gastroenterology 2009; 136:2051-4. PubMed
  • Verzi MP,Stanfel MN,Moses KA,Kim BM,Zhang Y,Schwartz RJ,Shivdasani RA,Zimmer WE. Role of the homeodomain transcription factor Bapx1 in mouse distal stomach development. Gastroenterology 2009; 136:1701-10. PubMed
  • Wuelling M,Kaiser FJ,Buelens LA,Braunholz D,Shivdasani RA,Depping R,Vortkamp A. Trps1, a regulator of chondrocyte proliferation and differentiation, interacts with the activator form of Gli3. Dev Biol 2009; 328:40-53. PubMed
  • Eeckhoute J,Lupien M,Meyer CA,Verzi MP,Shivdasani RA,Liu XS,Brown M. Cell-type selective chromatin remodeling defines the active subset of FOXA1-bound enhancers. Genome Res 2009; 19:372-80. PubMed
  • MacConaill LE, Campbell CD, Kehoe SM, Bass AJ, Hatton C, Niu L, Davis M, Yao K, Hanna M, Mondal C, Luongo L, Emery CM, Baker AC, Philips J, Goff DJ, Fiorentino M, Rubin MA, Polyak K, Chan J, Wang Y, Fletcher JA, Santagata S, Corso G, Roviello F, Shivdasani R, Kieran MW, Ligon KL, Stiles CD, Hahn WC, Meyerson ML, Garraway LA. Profiling critical cancer gene mutations in clinical tumor samples. PLoS ONE 2009; 4:e7887. PubMed
  • Firestein R,Bass AJ,Kim SY,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 beta-catenin activity. Nature 2008; 455:547-51. PubMed
  • Verzi MP,Khan AH,Ito S,Shivdasani RA. Transcription factor foxq1 controls mucin gene expression and granule content in mouse stomach surface mucous cells. Gastroenterology 2008; 135:591-600. PubMed
  • Kulke MH,Freed E,Chiang DY,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
  • Schulze H, Dose M, Korpal M, Meyer I, Italiano JE Jr, Shivdasani RA. RanBP10 Is a Cytoplasmic Guanine Nucleotide Exchange Factor That Modulates Noncentrosomal Microtubules. J Biol Chem 2008; 283:14109-19. 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; 28:3208-18. PubMed
  • Huang G, Zhang P, Hirai H, Elf S, Yan X, Chen Z, Koschmieder S, Okuno Y, Dayaram T, Growney JD, Shivdasani RA, Gilliland DG, Speck NA, Nimer SD, Tenen DG. PU.1 is a major downstream target of AML1 (RUNX1) in adult mouse hematopoiesis. Nat Genet 2007; 40:51-60. PubMed
  • Van Dyck F, Braem CV, Chen Z, Declercq J, Deckers R, Kim BM, Ito S, Wu MK, Cohen DE, Dewerchin M, Derua R, Waelkens E, Fiette L, Roebroek A, Schuit F, Van de Ven WJ, Shivdasani RA. Loss of the PlagL2 transcription factor affects lacteal uptake of chylomicrons. Cell Metab 2007; 6:406-13. PubMed
  • Kim BM, 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; 134:3603-13. PubMed
  • Junt T, Schulze H, Chen Z, Massberg S, Goerge T, Krueger A, Wagner DD, Graf T, Italiano JE, Shivdasani RA, von Andrian UH. Dynamic visualization of thrombopoiesis within bone marrow. Science 2007; 317:1767-70. PubMed
  • Kim BM, Mao J, Taketo MM, Shivdasani RA. Phases of canonical Wnt signaling during the development of mouse intestinal epithelium. Gastroenterology 2007; 133:529-38. PubMed
  • Chen Z, Naveiras O, Balduini AA, 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; 110:171-9. PubMed
  • Chen Z, Hu M, Shivdasani RA. Expression analysis of primary mouse megakaryocyte differentiation and its application in identifying stage-specific molecular markers and a novel transcriptional target of NF-E2. Blood 2006; 109:1451-9. 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; 133:4119-29. PubMed
  • Schulze H, Korpal M, Hurov J, Kim SW, Zhang J, Cantley LC, Graf T, Shivdasani RA. Characterization of the megakaryocyte demarcation membrane system and its role in thrombopoiesis. Blood 2006; 107:3868-75. PubMed
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