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 | Miguel Ramalho-Santos, Ph.D., M.Sc.
Assistant Professor Embryonic stem cells reside in the early mammalian embryo and have the ability to give rise to all cell types of the body. For this reason they are called pluripotent. Our lab is interested in understanding the genetic regulation of pluripotency. By identifying the molecular mechanisms that regulate pluripotency, two very important avenues of research will be open: 1 - it may be possible to tailor the differentiation of embryonic stem cells to particular cell types of choice that are need by patients, such as insulin-producing beta-cells in the case of diabetes; 2 - it may also be possible to reprogram cells from patients to become pluripotent like embryonic stem cells. This will allow the generation of patient-matched embryonic stem cells that would not be rejected upon transplantation. My lab is pursuing projects in the two avenues above. We are investigating how the transcriptional program for pluripotency is maintained in pluripotent cells and how it can be revived in differentiated cells. We study the mechanisms that regulate pluripotency in embryonic stem cells and the embryonic germline, which is also pluripotent. We use techniques such as mouse genetics and embryology, microarrays, bioinformatics, mouse and human embryonic stem cell manipulation and RNA interference. Selected Publication List: Ramalho-Santos, M., Melton, D. A., McMahon, A. P. (2000) Hedgehog signals regulate multiple aspects of gastrointestinal development. Development 127:2763-2772 Zhang, X. M., Ramalho-Santos, M., McMahon, A. P. (2001) Smoothened mutants reveal redundant roles for Shh and Ihh signaling including regulation of L/R asymmetry by the mouse node. Cell 105:781-792 Ramalho-Santos, M., Yoon, S., Matsuzaki, Y., Mulligan, R. C., Melton, D. A. (2002) ‘Stemness’: transcriptional profiling of embryonic and adult stem cells. Science 298:597-600 Ramalho-Santos, M.* (2004) Stem cells as probabilistic self-producing entities. Bioessays 26:1013-6 Heidersbach, A., Gaspar-Maia, A., McManus, M., Ramalho-Santos, M.* (2006) RNA interference in embryonic stem cells and the prospects for future therapies. Gene Therapy 13:478-86 Ramalho-Santos, M.* , Willenbring, H. (2007) On the origin of the term ‘stem cell’. Cell Stem Cell 1:35-38 Grskovic, M., Chaivorapol, C., Gaspar-Maia, A., Li, H.*, Ramalho-Santos, M.* (2007) Systematic identification of cis-regulatory sequences active in mouse and human embryonic stem cells. PLoS Genetics 3:1524-1540 Blelloch, R., Venere, M., Yen, J., Ramalho-Santos, M.* (2007) Generation of induced pluripotent stem cells in the absence of drug selection. Cell Stem Cell 1:245-247 Wong, C. 1, Gaspar-Maia, A., Ramalho-Santos, M.1*, Reijo Pera, R.* (2008) High-efficiency stem cell fusion-mediated assay reveals Sall4 as an enhancer of reprogramming. PLoS ONE(In press) Wei, G., Yeh, R.-F., Hebrok, M., Ramalho-Santos, M.* (2008) Maintenance of the transcriptional program for pluripotency in the embryonic germline: implications for reprogramming and tumorigenesis. (Submitted) * - corresponding author 1 - equal contribution |
