J. Richard Chaillet, M.D., Ph.D.


J. Chaillet Associate Professor
E1240 BSTWR
200 Lothrop Street
Pittsburgh, Pennsylvania 15261

Phone: (412) 383-7974
Fax: (412) 624-1401
E-mail: chaillet@pitt.edu

Lab Phone: (412) 383-7986

Biography


      Dr. Chaillet received his M.D. and Ph.D. degrees from Yale University in 1984. He joined the Department of Biological Sciences at the University of Pittsburgh in 1994, and moved to Microbiology and Molecular Genetics in 2003.

Research


      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.

Selected Publications


  • Cirio MC, Martel J, Mann M, Toppings M, Bartolomei M, Trasler J, Chaillet JR. (2008) "DNA methyltransferase 1o functions during preimplantation development to preclude a profound level of epigenetic variation" Dev Biol. 324:139-50. | Abstract


  • D'Aiuto L, Robison CS, Gigante M, Nwanegbo E, Shaffer B, Sukhwani M, Castro CA, Chaillet JR. (2008) "Human IL-12 p40 as a reporter gene for high-throughput screening of engineered mouse embryonic stem cells" BMC Biotechnol. 8:52. | Abstract


  • Paoloni-Giacobino A, Chaillet JR. (2007) "Evolutionary appearance of mononucleotide repeats in the coding sequences of four genes in primates" J Genet. 86:279-83. | Abstract


  • Toppings M, Castro C, Mills PH, Reinhart B, Schatten G, Ahrens ET, Chaillet JR, Trasler JM. (2008) "Profound phenotypic variation among mice deficient in the maintenance of genomic imprints" Hum Reprod. 23:807-18. | Abstract


  • Reinhart B, Paoloni-Giacobino A, Chaillet JR. (2006) Specific differentially methylated domain sequences direct the maintenance of methylation at imprinted genes. Mol Cell Biol. 26:8347-56. | Abstract



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