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.1995Biology
    University of Coimbra, PortugalM.Sc.1997Biology
    Harvard UniversityPh.D.2002Molecular and Cellular Biology

    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.

    Collapse Research 
    Collapse Research Activities and Funding
    Regulation of developmental potency by the transposon LINE1
    NIH/NIGMS R01GM123556May 19, 2017 - Feb 28, 2021
    Role: Principal Investigator
    Role of Chd1 in the transcriptional output and development of pluripotent cells
    NIH/NIGMS R01GM113014Feb 1, 2015 - Jan 31, 2019
    Role: Principal Investigator
    Environmental Modulation of Epigenetic Reprogramming in Pluripotent Cells
    NIH R01OD012204Jul 15, 2012 - Jun 30, 2017
    Role: Principal Investigator
    Role of pluripotency in development of the germline
    NIH DP2OD004698Sep 30, 2008 - Aug 31, 2013
    Role: Principal Investigator

    Collapse ORNG Applications 
    Collapse Websites

    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. Ebata KT, Mesh K, Liu S, Bilenky M, Fekete A, Acker MG, Hirst M, Garcia BA, Ramalho-Santos M. Vitamin C induces specific demethylation of H3K9me2 in mouse embryonic stem cells via Kdm3a/b. Epigenetics Chromatin. 2017; 10:36. PMID: 28706564.
      View in: PubMed
    2. Shenoy TR, Boysen G, Wang MY, Xu QZ, Guo W, Koh FM, Wang C, Zhang LZ, Wang Y, Gil V, Aziz S, Christova R, Rodrigues DN, Crespo M, Rescigno P, Tunariu N, Riisnaes R, Zafeiriou Z, Flohr P, Yuan W, Knight E, Swain A, Ramalho-Santos M, Xu DY, de Bono J, Wu H. CHD1 loss sensitizes prostate cancer to DNA damaging therapy by promoting error-prone double-strand break repair. Ann Oncol. 2017 Jul 01; 28(7):1495-1507. PMID: 28383660.
      View in: PubMed
    3. Percharde M, Wong P, Ramalho-Santos M. Global Hypertranscription in the Mouse Embryonic Germline. Cell Rep. 2017 Jun 06; 19(10):1987-1996. PMID: 28591571.
      View in: PubMed
    4. Percharde M, Bulut-Karslioglu A, Ramalho-Santos M. Hypertranscription in Development, Stem Cells, and Regeneration. Dev Cell. 2017 Jan 09; 40(1):9-21. PMID: 27989554.
      View in: PubMed
    5. Bulut-Karslioglu A, Biechele S, Jin H, Macrae TA, Hejna M, Gertsenstein M, Song JS, Ramalho-Santos M. Inhibition of mTOR induces a paused pluripotent state. Nature. 2016 12 01; 540(7631):119-123. PMID: 27880763.
      View in: PubMed
    6. 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; PMCID: PMC4807727.
    7. 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; PMCID: PMC4674342 [Available on 10/01/16].
    8. 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 07; 112(14):E1734-43. PMID: 25831528; PMCID: PMC4394284.
    9. 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 01; 142(1):118-27. PMID: 25480920; PMCID: PMC4299150.
    10. 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.
    11. 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.
    12. 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):449-461. PMID: 25036638; PMCID: PMC4130998.
    13. 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.
    14. 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.
    15. 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 08; 500(7461):222-6. PMID: 23812591; PMCID: PMC3893718.
    16. 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.
    17. 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.
    18. 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.
    19. 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 01; 21(9):2054-67. PMID: 22286172; PMCID: PMC3315209.
    20. 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.
    21. 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.
    22. 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.
    23. Ramalho-Santos M. iPS cells: insights into basic biology. Cell. 2009 Aug 21; 138(4):616-8. PMID: 19703387; PMCID: PMC3891582.
    24. 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.
    25. 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 Oct 27; 9:455. PMID: 18950538; PMCID: PMC2605473.
    26. 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 Apr 16; 3(4):e1955. PMID: 18414659; PMCID: PMC2278370.
    27. 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.
    28. 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.
    29. Ramalho-Santos M, Willenbring H. On the origin of the term "stem cell". Cell Stem Cell. 2007 Jun 07; 1(1):35-8. PMID: 18371332.
      View in: PubMed
    30. 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
    31. Ramalho-Santos M. Stem cells as probabilistic self-producing entities. Bioessays. 2004 Sep; 26(9):1013-6. PMID: 15351971.
      View in: PubMed
    32. 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
    33. 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
    34. 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
    35. 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
    36. 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
    37. 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 01; 274(40):28724-9. PMID: 10497243.
      View in: PubMed
    38. 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 01; 255(1):133-8. PMID: 9692911.
      View in: PubMed
    39. 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.
      View in: PubMed
    40. 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
    41. 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
    42. 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.
      View in: PubMed
    43. 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.
      View in: PubMed
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