|
||||||||||
Manuel
O.
Díaz,. M.D.
|
 |
|||||||||
|
I am interested in understanding the role of fusion genes generated by chromosome translocations in human leukemia. MLL is a gene involved in such fusions, and the subject of research in my laboratory. We have focused on the role of conserved domains of MLL protein that are important in transcriptional activation of target genes, or alternatively in the repression of target genes. The protein Cyp33 that interacts with a conserved domain of MLL, can promote a switch in function of MLL from transcriptional activator to repressor. We have proposed that Cyp33, an RNA binding protein may be part of a mechanism that modulates the function of MLL in the presence of specific non-coding regulatory RNAs. Another question we are asking is how do the chromosome translocations that give rise to MLL-fusion genes arise, and we are exploring the hypothesis that they arise through defective repair of DNA breaks introduced by apoptotic enzymes in the middle of the MLL gene. In collaboration with Andrew Vaughan, we have been able to produce translocations and fusion genes in cells cultured in vitro and subjected to treatments that initiate the apoptotic process. A fraction of the cells that abort apoptosis and survive these treatments, give rise to progeny with translocations that fuse MLL to other genes. This gives us an in vitro system where we can explore the details of the breakage and repair mechanisms involved. Selected PublicationsVaughan, A.T., Betti, C.J., Villalobos, M.J., Premkumar, K., Cline, E., Jiang, Q., Diaz, M.O.: Surviving apoptosis: A possible mechanism of benzene-induced leukemia. Chem. Biol. Interact. 153-154:179-185, (2005). Xia, Z.B., Popovic, R., Chen, J., Theisler, C., Stuart, T., Santillan, D.A., Erfurth, F., Diaz, M.O., Zeleznik-Le, N.J.: The MLL fusion gene, MLL-AF4, regulates cyclin-dependent kinase inhibitor CDKN1B (p27kip1) expression. Proc Natl Acad Sci U S A. 102:14028-14033, (2005). Betti, C.J., Villalobos, M.J., Jiang, Q., Cline, E., Diaz, M.O., Loredo, G., Vaughan, A.T.M.: Cleavage of the MLL gene by activators of apoptosis is independent of topoisomerase II activity. Leukemia. 19:2289-2295, (2005).Xia Z, Anderson M, Diaz, M.O., Zeleznik-Le, N.J.: MLL repression domain activity is mediated by histone deacetylases, the polycomb group proteins HPC2 and BMI-1, and the corepressor CtBP. Proc. Natl. Acad. Sci. USA 100:8342-8347, (2003). Betti, C.J., Villalobos, M.J., Diaz, M.O., Vaughan, A.T.M.: Apoptotic stimuli initiate MLL-AF9 translocations that are transcribed in cells capable of division. Cancer Research. 63:1377-1381, (2003). Search PubMed for a complete listing of Manuel Díaz's publications.
| ||||||||||
/ SSOM / Loyola University Chicago / LUHS / Contact Us
©1995-2008
Loyola University Health System. All rights reserved.
|
||||||||||
