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    Miguel Ramalho-Santos, PhD

    TitleAssociate Professor
    SchoolUCSF School of Medicine
    DepartmentOb/Gyn, Reproductive Sciences
    Address35 Medical Center Way
    San Francisco CA 94143
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      Collapse Biography 
      Collapse Education and Training
      University of Coimbra, PortugalB.S.Biology1995
      University of Coimbra, PortugalM.Sc.Biology1997
      Harvard UniversityPh.D.Molecular and Cellular Biology2002

      Collapse Overview 
      Collapse Overview
      Pluripotency is the remarkable ability that certain stem cells have of giving rise to all cell types of the body. The molecular regulation of pluripotency is a fundamental basic biology question with important potential implications in Regenerative Medicine, Reproductive Biology and Cancer. We are investigating how the chromatin state and the transcriptional program for pluripotency are maintained in pluripotent stem cells and how they can be revived during reprogramming, in both mouse and human cells. We study the epigenetic regulation of stem cell pluripotency in vivo using mouse models, focusing on early embryonic development and the germline. We use approaches from mouse genetics and embryology, stem cell biology, reprogramming, functional genomics, epigenetics and bioinformatics.

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      Collapse Bibliographic 
      Collapse Publications
      Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
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      1. Qin H, Hejna M, Liu Y, Percharde M, Wossidlo M, Blouin L, Durruthy-Durruthy J, Wong P, Qi Z, Yu J, Qi LS, Sebastiano V, Song JS, Ramalho-Santos M. YAP Induces Human Naive Pluripotency. Cell Rep. 2016 Mar 15; 14(10):2301-12. PMID: 26947063.
        View in: PubMed
      2. Biechele S, Lin CJ, Rinaudo PF, Ramalho-Santos M. Unwind and transcribe: chromatin reprogramming in the early mammalian embryo. Curr Opin Genet Dev. 2015 Oct; 34:17-23. PMID: 26183187.
        View in: PubMed
      3. Koh FM, Lizama CO, Wong P, Hawkins JS, Zovein AC, Ramalho-Santos M. Emergence of hematopoietic stem and progenitor cells involves a Chd1-dependent increase in total nascent transcription. Proc Natl Acad Sci U S A. 2015 Apr 7; 112(14):E1734-43. PMID: 25831528; PMCID: PMC4394284.
      4. Guzman-Ayala M, Sachs M, Koh FM, Onodera C, Bulut-Karslioglu A, Lin CJ, Wong P, Nitta R, Song JS, Ramalho-Santos M. Chd1 is essential for the high transcriptional output and rapid growth of the mouse epiblast. Development. 2015 Jan 1; 142(1):118-27. PMID: 25480920; PMCID: PMC4299150 [Available on 01/01/16].
      5. Diaz AA, Qin H, Ramalho-Santos M, Song JS. HiTSelect: a comprehensive tool for high-complexity-pooled screen analysis. Nucleic Acids Res. 2015 Feb 18; 43(3):e16. PMID: 25428347; PMCID: PMC4330337.
      6. Lin CJ, Koh FM, Wong P, Conti M, Ramalho-Santos M. Hira-mediated H3.3 incorporation is required for DNA replication and ribosomal RNA transcription in the mouse zygote. Dev Cell. 2014 Aug 11; 30(3):268-79. PMID: 25087892; PMCID: PMC4134436.
      7. Qin H, Diaz A, Blouin L, Lebbink RJ, Patena W, Tanbun P, LeProust EM, McManus MT, Song JS, Ramalho-Santos M. Systematic identification of barriers to human iPSC generation. Cell. 2014 Jul 17; 158(2):449-61. PMID: 25036638; PMCID: PMC4130998.
      8. Chen J, Torcia S, Xie F, Lin CJ, Cakmak H, Franciosi F, Horner K, Onodera C, Song JS, Cedars MI, Ramalho-Santos M, Conti M. Somatic cells regulate maternal mRNA translation and developmental competence of mouse oocytes. Nat Cell Biol. 2013 Dec; 15(12):1415-23. PMID: 24270888; PMCID: PMC4066669.
      9. Lin CJ, Conti M, Ramalho-Santos M. Histone variant H3.3 maintains a decondensed chromatin state essential for mouse preimplantation development. Development. 2013 Sep; 140(17):3624-34. PMID: 23903189; PMCID: PMC3742145.
      10. Blaschke K, Ebata KT, Karimi MM, Zepeda-Martínez JA, Goyal P, Mahapatra S, Tam A, Laird DJ, Hirst M, Rao A, Lorincz MC, Ramalho-Santos M. Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells. Nature. 2013 Aug 8; 500(7461):222-6. PMID: 23812591; PMCID: PMC3893718.
      11. Sachs M, Onodera C, Blaschke K, Ebata KT, Song JS, Ramalho-Santos M. Bivalent chromatin marks developmental regulatory genes in the mouse embryonic germline in vivo. Cell Rep. 2013 Jun 27; 3(6):1777-84. PMID: 23727241; PMCID: PMC3700580.
      12. Sakaki-Yumoto M, Liu J, Ramalho-Santos M, Yoshida N, Derynck R. Smad2 is essential for maintenance of the human and mouse primed pluripotent stem cell state. J Biol Chem. 2013 Jun 21; 288(25):18546-60. PMID: 23649632; PMCID: PMC3689995.
      13. Hunkapiller J, Shen Y, Diaz A, Cagney G, McCleary D, Ramalho-Santos M, Krogan N, Ren B, Song JS, Reiter JF. Polycomb-like 3 promotes polycomb repressive complex 2 binding to CpG islands and embryonic stem cell self-renewal. PLoS Genet. 2012; 8(3):e1002576. PMID: 22438827; PMCID: PMC3305387.
      14. Qin H, Blaschke K, Wei G, Ohi Y, Blouin L, Qi Z, Yu J, Yeh RF, Hebrok M, Ramalho-Santos M. Transcriptional analysis of pluripotency reveals the Hippo pathway as a barrier to reprogramming. Hum Mol Genet. 2012 May 1; 21(9):2054-67. PMID: 22286172; PMCID: PMC3315209.
      15. Ohi Y, Qin H, Hong C, Blouin L, Polo JM, Guo T, Qi Z, Downey SL, Manos PD, Rossi DJ, Yu J, Hebrok M, Hochedlinger K, Costello JF, Song JS, Ramalho-Santos M. Incomplete DNA methylation underlies a transcriptional memory of somatic cells in human iPS cells. Nat Cell Biol. 2011 May; 13(5):541-9. PMID: 21499256; PMCID: PMC3987913.
      16. Gaspar-Maia A, Alajem A, Meshorer E, Ramalho-Santos M. Open chromatin in pluripotency and reprogramming. Nat Rev Mol Cell Biol. 2011 Jan; 12(1):36-47. PMID: 21179060; PMCID: PMC3891572.
      17. Koh FM, Sachs M, Guzman-Ayala M, Ramalho-Santos M. Parallel gateways to pluripotency: open chromatin in stem cells and development. Curr Opin Genet Dev. 2010 Oct; 20(5):492-9. PMID: 20598875; PMCID: PMC2943036.
      18. Ramalho-Santos M. iPS cells: insights into basic biology. Cell. 2009 Aug 21; 138(4):616-8. PMID: 19703387; PMCID: PMC3891582.
      19. Gaspar-Maia A, Alajem A, Polesso F, Sridharan R, Mason MJ, Heidersbach A, Ramalho-Santos J, McManus MT, Plath K, Meshorer E, Ramalho-Santos M. Chd1 regulates open chromatin and pluripotency of embryonic stem cells. Nature. 2009 Aug 13; 460(7257):863-8. PMID: 19587682; PMCID: PMC3891576.
      20. Chaivorapol C, Melton C, Wei G, Yeh RF, Ramalho-Santos M, Blelloch R, Li H. CompMoby: comparative MobyDick for detection of cis-regulatory motifs. BMC Bioinformatics. 2008; 9:455. PMID: 18950538; PMCID: PMC2605473.
      21. Wong CC, Gaspar-Maia A, Ramalho-Santos M, Reijo Pera RA. High-efficiency stem cell fusion-mediated assay reveals Sall4 as an enhancer of reprogramming. PLoS One. 2008; 3(4):e1955. PMID: 18414659; PMCID: PMC2278370.
      22. Blelloch R, Venere M, Yen J, Ramalho-Santos M. Generation of induced pluripotent stem cells in the absence of drug selection. Cell Stem Cell. 2007 Sep 13; 1(3):245-7. PMID: 18371358; PMCID: PMC2894698.
      23. Grskovic M, Chaivorapol C, Gaspar-Maia A, Li H, Ramalho-Santos M. Systematic identification of cis-regulatory sequences active in mouse and human embryonic stem cells. PLoS Genet. 2007 Aug; 3(8):e145. PMID: 17784790; PMCID: PMC1959362.
      24. Ramalho-Santos M, Willenbring H. On the origin of the term "stem cell". Cell Stem Cell. 2007 Jun 7; 1(1):35-8. PMID: 18371332.
        View in: PubMed
      25. Heidersbach A, Gaspar-Maia A, McManus MT, Ramalho-Santos M. RNA interference in embryonic stem cells and the prospects for future therapies. Gene Ther. 2006 Mar; 13(6):478-86. PMID: 16520820.
        View in: PubMed
      26. Ramalho-Santos M. Stem cells as probabilistic self-producing entities. Bioessays. 2004 Sep; 26(9):1013-6. PMID: 15351971.
        View in: PubMed
      27. Ramalho-Santos M, Yoon S, Matsuzaki Y, Mulligan RC, Melton DA. "Stemness": transcriptional profiling of embryonic and adult stem cells. Science. 2002 Oct 18; 298(5593):597-600. PMID: 12228720.
        View in: PubMed
      28. Zhang XM, Ramalho-Santos M, McMahon AP. Smoothened mutants reveal redundant roles for Shh and Ihh signaling including regulation of L/R symmetry by the mouse node. Cell. 2001 Jul 27; 106(2):781-92. PMID: 11517919.
        View in: PubMed
      29. Zhang XM, Ramalho-Santos M, McMahon AP. Smoothened mutants reveal redundant roles for Shh and Ihh signaling including regulation of L/R asymmetry by the mouse node. Cell. 2001 Jun 15; 105(6):781-92. PMID: 11440720.
        View in: PubMed
      30. Ramalho-Santos M, Melton DA, McMahon AP. Hedgehog signals regulate multiple aspects of gastrointestinal development. Development. 2000 Jun; 127(12):2763-72. PMID: 10821773.
        View in: PubMed
      31. Haggarty SJ, Ramalho-Santos M. Will cell alliance breed bureaucracy and leave contributors out? Nature. 2000 Feb 10; 403(6770):591. PMID: 10688171.
        View in: PubMed
      32. Faro C, Ramalho-Santos M, Vieira M, Mendes A, Simões I, Andrade R, Veríssimo P, Lin X, Tang J, Pires E. Cloning and characterization of cDNA encoding cardosin A, an RGD-containing plant aspartic proteinase. J Biol Chem. 1999 Oct 1; 274(40):28724-9. PMID: 10497243.
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      33. Ramalho-Santos M, Veríssimo P, Cortes L, Samyn B, Van Beeumen J, Pires E, Faro C. Identification and proteolytic processing of procardosin A. Eur J Biochem. 1998 Jul 1; 255(1):133-8. PMID: 9692911.
        View in: PubMed
      34. Ramalho-Santos M, Pissarra J, Pires E, Faro C. Cardosinogen A. The precursor form of the major aspartic proteinase from cardoon. Adv Exp Med Biol. 1998; 436:253-8. PMID: 9561227.
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      35. Veríssimo P, Ramalho-Santos M, Faro C, Pires E. A comparative study on the aspartic proteinases from different species of Cynara. Adv Exp Med Biol. 1998; 436:459-63. PMID: 9561253.
        View in: PubMed
      36. Faro C, Ramalho-Santos M, Veríssimo P, Pissarra J, Frazão C, Costa J, Lin XL, Tang J, Pires E. Structural and functional aspects of cardosins. Adv Exp Med Biol. 1998; 436:423-33. PMID: 9580379.
        View in: PubMed
      37. Ramalho-Santos M, Pissarra J, Veríssimo P, Pereira S, Salema R, Pires E, Faro CJ. Cardosin A, an abundant aspartic proteinase, accumulates in protein storage vacuoles in the stigmatic papillae of Cynara cardunculus L. Planta. 1997 Oct; 203(2):204-12. PMID: 9362566.
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      38. Ramalho-Santos M, Veríssimo P, Faro C, Pires E. Action on bovine alpha s1-casein of cardosins A and B, aspartic proteinases from the flowers of the cardoon Cynara cardunculus L. Biochim Biophys Acta. 1996 Sep 13; 1297(1):83-9. PMID: 8841384.
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