J. Richard Chaillet, Associate Professor
MD, Yale University School of Medicine, 1983
PhD, Yale University, 1984
Email: chaillet@pitt.edu
Research Interest:
Investigating the molecular mechanisms of epigenetic inheritance and genomic imprinting in mammals, and the roles these processes play in reprogramming the genome during preimplantation development. These processes largely involve directed developmental changes in DNA methylation.
Dr. Chaillet's research program focuses on three aspects of mammalian development: (1) genomic imprinting, a form of epigenetic inheritance; (2) the biology of mouse embryonic stem cells; and (3) the etiology of ovarian teratomas. (1) 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. (2) 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. (3) 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.
Recent Publication
Fan Y., Melhem MF, Chaillet JR. Forced expression of the homeobox-containing gene Pem blocks differentiation of embryonic stem cells. Developmental Biology 210:481-496, 1999.
Howell CY, Bestor TH, Ding F, Latham KE, Mertineit C, Trasler JM, Chaillet JR. Genomic imprinting disrupted by a maternal-effect mutation in the Dnmt1 gene. Cell 104:829-838, 2001.
Reinhart B, Eljanne M, Chaillet JR. Shared role for differentially methylated domains of imprinted genes. Molecular and Cellular Biology 22:2089-2098, 2002.
Ratnam S, Mertineit C, Ding F, Howell CY, Clarke HJ, Bestor TH, Chaillet JR, Trasler JM. Dynamics of Dnmt1 methyltransferase expression and intracellular localization during oogenesis and preimplantation development. Developmental Biology 245:304-314, 2002.
Ding F, Chaillet JR. In vivo stabilization of the Dnmt1 (cytosine-5)-methyltransferase protein. Proc National Acad Sci USA 99:14861-14866, 2002.
Ding F, Patel C, Ratnam S, McCarrey JR, Chaillet JR. Conservation of Dnmt1o cytosine methyltransferase in the marsupial Monodelphis domestica. genesis 36:209-213, 2003.
Chung YG, Ratnam S, Chaillet JR, Latham KE. Abnormal regulation of DNA methyltransferase expression in cloned mouse embryos. Biol Reprod 69:146-153, 2003.
Ben-Yehudah A, Reinhart B, Navara C, Kotzuk J, Witchel S, Schatten G, Chaillet JR. Specific dynamic and non-invasive labeling of pancreatic cells in reporter mice. genesis 43:166-174, 2005.
D'Aiuto L, De Marco R, Edward,N, Rizzo A, Chaillet JR, Montecalvo A, Lotze M, Gambotto A. Evidence of the capability of the CMV enhancer to activate in trans gene expression in mammalian cells. DNA and Cell Biology 25:171-180, 2006.
Reinhart B, Paoloni-Giacobino A, Chaillet JR. Specific differentially methylated domain sequences direct the maintenance of methylation at imprinted genes. Molecular and Cellular Biology 26:8347-8356, 2006.
Green K, Lewis A, Dawson C, Dean W, Reinhart B, Chaillet JR, Reik WA. A developmental window of opportunity for imprinted gene silencing mediated by DNA methylation and the Kcnq1ot1 non-coding RNA. Mammalian Genome 18:32-42, 2007.
