Research Interests:

Cancer biology

One interest of the lab is the role of transcription factors in cancer, in particular a family of transcription factors that appear to be involved in both cancer and normal development. These proteins contain a zinc finger DNA binding domain. They also have a POZ domain, a motif that mediates protein-protein interactions among family member and transcriptional repression. The protein that we work with is BCL-6. Inappropriate expression of BCL-6 is associated with diffuse large cell lymphoma. We are interested in determining what genes this repressor regulates and how it carries out repression. A second project involves the gene Dmrt1, which is likely to play a role in mammalian sex determination. The protein, DMRT1, is also a transcription factor and we are interested in how it regulates transcription, how it fits into the sex determination pathway.

Selected Recent Publications:

• Huynh, K.D., Fischle, W., Verdin, E. and Bardwell, V.J. (2000) BCoR, a novel corepressor involved in BCL-6 repression. Genes and Development 14(14):1810-1823.
• Ng, D., Thakker, N., Corcoran, C.M., Donnai, D., Perveen, R., Schneider, A., Hadley, D.W., Tifft, C., Zhang, L., Wilkie, A.O, Van Der Smagt, J.J., Gorlin, R.J., Burgess, S.M., Bardwell, V.J., Black, G.C. and Biesecker, L.G. (2004) Oculofaciocardiodental and Lenz microphthalmia syndromes result from distinct classes of mutations in BCOR. Nat Genet. 36(4):411-416.
• Winkler, G.S., Mulder, K.W., Bardwell, V.J., Kalkhoven, E. and Timmers, H.T. (2006) Human Ccr4-Not Complex Is a Ligand-Dependent Repressor of Nuclear Receptor-Mediated Transcription. (2006) EMBO J. 25(13):3089-3099.
  
• Gearhart, M.D., Corcoran, C.M., Wamstad, J.A. and Bardwell, V.J. (2006) Polycomb Group and SCF ubiquitin ligases are present in a BCL6 corepressor complex. Mol. Cell. Biol. 26(18):6880-6889.
• Balciuniene, J., Bardwell, V.J. and Zarkower, D. (2006) Mice mutant in the DM domain gene Dmrt4 are viable and fertile but have polyovular follicles. Mol. Cell. Biol. 26(23):8984-8991.
• Arrigoni, R., Alam, S.L., Wamstad, J.A., Bardwell, V.J., Sundquist, W.I. and Schreiber-Agus, N. (2006) The Polycomb-associated protein Rybp is a ubiquitin binding protein. FEBS Lett. 580(26):6233-41.
• Fahrioglu, U., Murphy, M.M., Zarkower, D. and Bardwell, V.J. (2007) mRNA
  expression analysis and the molecular basis of neonatal testis defects in Dmrt1 mutant mice. Sex. Dev. 1(1):42-58.
• Wamstad, J.A., and Bardwell, V.J. (2007) Characterization of Bcor expression in mouse development. Gene Expr. Patterns 7(5):550-557.
• Kim, S., Namekawa, S.T., Niswander, L., Ward, J., Lee, J.T., Bardwell, V.J., and Zarkower, D. (2007) A mammal-specific Doublesex homolog is a component of male sex chromatin and is required for male meiosis. PLOS Genetics 3(4):e62.
• Kim, S., Bardwell, V.J., and Zarkower, D. (2007) Cell type-autonomous and
  non-autonomous requirements for Dmrt1 in postnatal testis differentiation. Dev Biol. 2007 307(2):314-27.
• Murphy, M.W., Zarkower, D. and Bardwell, V.J. (2007) Vertebrate DM domain proteins bind similar DNA sequences and can heterodimerize on DNA. BMC Molecular Biology 8:58.
• Hilton, E., Black, G. and Bardwell, V.J. (2008) The BCL-6 corepressor (BCOR) and Oculofaciocardiodental syndrome. (not peer reviewed) Chapter for the book Inborn Errors of Development, Charles Epstein, Editor, Oxford University Press (pages 987-994).
• Ghetu, A., CorcoranC.M., Cerchietti, L., BardwellV.J., Melnick, A., and Privé, G.G. (2008) Structure of a BCOR co-repressor peptide in a complex with the BCL6 BTB dimer. Molecular Cell 29(3):384-91.
• Wamstad, J.A., Corcoran, C.M., Keating, A.M. and Bardwell, V.J. (2008) Role of the Transcriptional Corepressor Bcor in ES Cell Differentiation and Early Embryonic Development. PLoS ONE. 30;3(7):e2814.
• Krentz AD, Murphy MW, Kim S, Cook MS, Capel B, Zhu R, Matin A, Sarver AL, Parker KL, Griswold MD, Looijenga LH, Bardwell VJ, Zarkower D. (2009) The DM domain protein DMRT1 is a dose-sensitive regulator of fetal germ cell proliferation and pluripotency. Proc Natl Acad Sci U S A 106(52):22323-8.
  
• Murphy, M.W., Sarver, A.L., Rice, D., Hatzi, K., Ye, K., Melnick, A., Heckert, L.L., Zarkower, D., Bardwell, V.J. (2010) Genome-wide analysis of DNA binding and transcriptional regulation by the mammalian Doublesex homolog DMRT1 in the juvenile testis. Proc Natl Acad Sci U S A. 107(30):13360-5.
• Matson, C.K., Murphy, M.W., Griswold, M.D., Yoshida, S., Bardwell, V.J., Zarkower, D. (2010) The mammalian doublesex homolog DMRT1 is a transcriptional gatekeeper that controls the mitosis versus meiosis decision in male germ cells. Dev Cell. 2010 19(4):612-24.
• Matson, C.K., Murphy, M.W., Sarver, A.L., Griswold, M.D., Bardwell, V.J., Zarkower, D. (2011) DMRT1 prevents female reprogramming in the postnatal mammalian testis. Nature 476(7358):101-4.