J. Richard Chaillet, MD, PhD
Associate Professor of Microbiology, Molecular Genetics and Biochemistry
Dr. Chaillet is an Associate Professor in the Department of Microbiology and Molecular Genetics and a member of the Cellular and Molecular Pathology Graduate Training Program.
Magee-Womens Research Institute
204 Craft Avenue
Pittsburgh, PA 15213
Office Telephone: 412-641-8166
Lab Telephone: 412-641-8167
- MD - Yale University, 1983
- PhD - Yale University, 1984
Research InterestsMy research interests are in the subject of epigenetic inheritance in mammalian species. This type of inheritance involves the establishment and maintenance (inheritance) of CpG methylation patterns associated with a variety of different gene sequences. The best known examples of this are imprinted genes, which are genes expressed from one parental allele due to the establishment of a methylation pattern (imprint) on just one of the parental alleles (maternal or paternal allele) in the gametes ( egg or sperm). Like DNA sequence itself, these imprints are inherited and affect gene expression during embryogenesis. Epigenetic inheritance is also important for pluripotency of the embryo’s stem cells and for reprogramming the genome of the zygote to the pluripotent state of cells in the blastocyst.
My laboratory studies the molecular mechanisms of epigenetic inheritance, using the mouse as the experimental organism. Our recent efforts have focused on the role of the DNA cytosine methyltransferase DNMT1 in the inheritance of genomic imprints and remodeling the genome’s methylation during early embryogenesis and on the role of DNMT1 in placental development and function.
Selected PublicationsView Dr. Chaillet's publications on PubMed
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. Developmental Biology 324, 139-150.
Ben-Yehudah, A., White, C., Navara, C.S., Castro, C.A., Ize-Ludlow, D., Shaffer, B., Sukhwani, M., Mathews, C.E., Chaillet, J.R., and Witchel, S.F. (2009) Evaluating protocols for embryonic stem cell differentiation into insulin secreting b-cells using Insulin II-GFP as a specific and non-invasive reporter. Cloning and Stem Cells 11, 245-257.
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.
D’Aiuto, L., Marzulli, M., Mohan, K.N., Borowczyk, E., Saporiti, F., VanDemark, A., and Chaillet, J.R. (2010) Dissection of structure and function of the N-terminal domain of mouse DNMT1 using Regional Frame-Shift Mutagenesis. PLosONE 5(3):e9831.
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.
Mohan, K.N., Ding, F., Chaillet, J.R. (2011) Distinct roles of DMAP1 in mouse development. Mol. Cell. Biol. 31, 1861-1869.
D’Aiuto, L.D., Di Maio, R., Mohan, K.N., Minervini, C., Saporiti, F, Soreca, I., Greenamyre, J.T., and Chaillet, J.R. (2011) Mouse ES cells overexpressing DNMT1 produce abnormal neurons with upregulated NMDA/NR1 subunit. Differentiation 82, 9-17.