Among the changes that occur during pregnancy, those affecting the breasts have been found to subsequently modify breast cancer risk. My laboratory investigates how the signals present during pregnancy permanently alter the way gene expression is controlled and how these changes affect normal and malignant mammary development.
Camila dos Santos’ laboratory studies the epigenetic regulation of normal and malignant mammary gland development, with an emphasis on the alterations brought by pregnancy. Significant changes mark the pre- and post-pubescence mammary developmental stages, but those associated with pregnancy have the greatest effect on cellular function, tissue reorganization, and breast cancer susceptibility. Her group has recently found that mammary glands react differently to a second pregnancy than they do to the first one, with associated changes in DNA methylation. These findings suggested that pregnancy changes the state of mammary cells, and these may permanently alter how they react to the next pregnancy. In addition, the dos Santos lab is exploring how the pregnancy-induced epigenetic changes might influence cell transformation and the risk of breast cancer. This research utilizes genomic and computational approaches to define the pre and post-pregnancy mammary epigenome. An additional objective of the dos Santos’ laboratory is to use functional genomics to discover novel transcriptional regulators that modulate mammary stem cell self-renewal, lineage specification, and cell transformation. The long-term objective of Camila’s group is to improve the notion of the mammary epigenome during normal development and use this information to gain insight into new preventive and curative strategies to target breast cancer.
The V Foundation: V Scholar Award
Urick, A. K. and Hawk, L. M. and Cassel, M. K. and Mishra, N. K. and Liu, S. and Adhikari, N. and Zhang, W. and Dos Santos, C. O. and Hall, J. L. and Pomerantz, W. C. (2015) Dual Screening of BPTF and Brd4 Using Protein-Observed Fluorine NMR Uncovers New Bromodomain Probe Molecules. ACS Chem Biol, 10(10) pp. 2246-56.
Dos Santos, C. O. and Dolzhenko, E. and Hodges, E. and Smith, A. D. and Hannon, G. J. (2015) An Epigenetic Memory of Pregnancy in the Mouse Mammary Gland. Cell Reports,
Dos Santos, C. O. and Rebbeck, C. and Rozhkova, E. and Valentine, A. and Samuels, A. and Kadiri, L. R. and Osten, P. and Harris, E. Y. and Uren, P. J. and Smith, A. D. and Hannon, G. J. (2013) Molecular hierarchy of mammary differentiation yields refined markers of mammary stem cells. Proceedings of the National Academy of Sciences of the United States of America, 110(18) pp. 7123-7130.
Hodges, E. and Molaro, A. and Dos Santos, C. O. and Thekkat, P. and Song, Q. and Uren, P. J. and Park, J. H. and Butler, J. and Rafii, S. and McCombie, W. R. and Smith, A. D. and Hannon, G. J. (2011) Directional DNA Methylation Changes and Complex Intermediate States Accompany Lineage Specificity in the Adult Hematopoietic Compartment. Molecular Cell, 44(1) pp. 17-28.
Obad, S. and Dos Santos, C. O. and Petri, A. and Heidenblad, M. and Broom, O. and Ruse, C. and Fu, C. and Lindow, M. and Stenvang, J. and Straarup, E. M. and Hansen, H. F. and Koch, T. and Pappin, D. and Hannon, G. J. and Kauppinen, S. (2011) Silencing of microRNA families by seed-targeting tiny LNAs. Nature Genetics, 43(4) pp. 371-380.Additional materials of the author at
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