J. Richard Chaillet, MD, PhD
B703 Magee Womens Research Institute
204 Craft Avenue
MD, Yale University
PhD in Physiology, Yale University
Dr. Chaillet’s research program focuses on three aspects of mammalian development:
- genomic imprinting, a form of epigenetic inheritance;
- the biology of mouse embryonic stem cells;
- the etiology of ovarian teratomas.
Genomic imprinting distinguishes alleles of mammalian genes by their parental origins and their epigenetic modifications. One of the parental alleles of an imprinted gene is transcriptionally active and epigenetically marked in a characteristic way, whereas the opposite allele is silent and marked in a different way. My laboratory is primarily interested in the molecular mechanism of genomic imprinting and the developmental consequences of disrupting the imprinting process in the fetus. We use a number of mouse models, including transgenic and knockout mice, to explore these important issues. My laboratory is also interested in a number of aspects of mouse embryonic stem (ES) cells, including identifying the molecular pathways that are used to maintain the undifferentiated, pluripotent state of ES cells; directing ES cells to differentiate into endodermal cell types; and studying the effects of altered genomic imprinting on the ability of ES cells to contribute to normal fetal development.
Ovarian teratomas develop when maturing oocytes in the ovary spontaneously activate in the absence of fertilization, start dividing and enter into an embryonic developmental program. The pattern of cell and tissue differentiation within a growing teratoma involves all three primary embryonic cell lineages (endoderm, ectoderm and mesoderm). My laboratory studies the genetic and molecular bases of these tumors by utilizing transgenic and inbred mouse lines that are prone to developing ovarian teratomas. In summary, the three aspects of mammalian development that we are studying are interdependent approaches to elucidating the essential molecular mechanisms controlling early mammalian development, genome reprogramming and the establishment of pluripotent embryo stem cells.
Mohan, K. N; Ding, F; and Chaillet, J. R. (2011) Distinct roles of DMAP1 in mouse development. Mol Cell Biol. 31: 1861-1869. | View Abstract
Rugo, R. E; Mutamba, J. T; Mohan, K. N; Yee, T; Chaillet, J. R; Greenberger, J. S; and Engelward, B. P. (2011) Methyltransferases mediate cell memory of a genotoxic insult. Oncogene. 30: 751-756. | View Abstract
Borowczyk, E; Mohan, K. N; D'Aiuto, L; Cirio, M. C; and Chaillet, J. R. (2009) Identification of a region of the DNMT1 methyltransferase that regulates the maintenance of genomic imprints. Proc Natl Acad Sci USA. 106: 20806-20811. | View Abstract
Cirio, M. C; Martel, J; Mann, M; Toppings, M; Bartolomei, M; Trasler, J; and Chaillet, J. R. (2008) DNA methyltransferase 1o functions during preimplantation development to preclude a profound level of epigenetic variation. Dev Biol. 324: 139-150. | View Abstract
Reinhart, B; Paoloni-Giacobino, A; and Chaillet, J. R. (2006) Specific differentially methylated domain sequences direct the maintenance of methylation at imprinted genes. Mol Cell Biol. 26: 8347-8356. | View Abstract
Ding, F; and Chaillet, J. R. (2002) In vivo stabilization of the Dnmt1 (cytosine-5)- methyltransferase protein. Proc Natl Acad Sci USA. 99: 14861-14866. | View Abstract
Howell, C. Y; Bestor, T. H; Ding, F; Latham, K. E; Mertineit, C; Trasler, J. M; and Chaillet, J. R. (2001) Genomic imprinting disrupted by a maternal effect mutation in the Dnmt1 gene. Cell. 104: 829-838. | View Abstract