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RESEARCH FOCUS AREAS:
- MLL and MLL fusion proteins
- Leukemogenesis
RESEARCH SUMMARY:
Dr. Diaz's research activities focus on the mechanisms that lead to leukemia development by mutant proteins that arise from mutations of the MLL gene. This is primarily through the function of the normal MLL protein, and how the mutant MLL-fusion proteins differ from the normal MLL in their function. Since these proteins regulate the expression of a subset of genes that are master regulators of cell proliferation and differentiation during development, studies are directed toward the effect of MLL mutations on the development of blood cells, and especially on the transition from blood stem cells to the lineages of differentiated blood cells. This transition is altered in all leukemias and understanding how MLL mutants affect it may allow understanding of a crucial initial step for leukemogenesis in general. This may be important not only to find appropriate targets for new and more specific therapies, but also to conceive new ways to reduce the incidence of leukemia by preventive measures.
EDUCATION:
MD University of the Republic, School of Medicine, Montevideo, Uruguay
SELECTED PUBLICATIONS:
- c-Myc-mediated control of cell fate in megakaryocyte-erythrocyte progenitors Guo, Y; Niu, C; Breslin, P; Tang, M; Zhang, S; Wei, W; Kini, AR; Paner, GP; Alkan, S; Morris, SW; Diaz, M; Stiff, PJ; Zhang, J Blood 2009 Sep 3;114(10):2097-106. doi: 10.1182/blood-2009-01-197947. Epub 2009 Apr 16. PMID: 19372257; PMCID: PMC2744571
- Loss of MLL PHD finger 3 is necessary for MLL-ENL-induced hematopoietic stem cell immortalization Chen, J; Santillan, DA; Koonce, M; Wei, W; Luo, R; Thirman, MJ; Zeleznik-Le, NJ; Diaz, MO Cancer Research 2008 Aug 1;68(15):6199-207. doi: 10.1158/0008-5472.CAN-07-6514. PMID: 18676843; PMCID: PMC2734520
- TAK1 is required for the survival of hematopoietic cells and hepatocytes in mice Tang, M; Wei, X; Guo, Y; Breslin, P; Zhang, S; Zhang, S; Wei, W; Xia, Z; Diaz, M; Akira, S; Zhang, J Journal of Experimental Medicine 2008 Jul 7;205(7):1611-9. doi: 10.1084/jem.20080297. Epub 2008 Jun 23. PMID: 18573910; PMCID: PMC2442639
- MLL protects CpG clusters from methylation within the Hoxa9 gene; maintaining transcript expression Erfurth, FE; Popovic, R; Grembecka, J; Cierpicki, T; Theisler, C; Xia, ZB; Stuart, T; Diaz, MO; Bushweller, JH; Zeleznik-Le, NJ Proceedings of the National Academy of Sciences U S A 2008 May 27;105(21):7517-22. doi: 10.1073/pnas.0800090105. Epub 2008 May 15. PMID: 18483194; PMCID: PMC2396713
- The MLL fusion gene; MLL-AF4; regulates cyclin-dependent kinase inhibitor CDKN1B (p27kip1) expression Xia, ZB; Popovic, R; Chen, J; Theisler, C; Stuart, T; Santillan, DA; Erfurth, F; Diaz, MO; Zeleznik-Le, N Proceedings of the National Academy of Sciences U S A 2005 Sep 27;102(39):14028-33. doi: 10.1073/pnas.0506464102. Epub 2005 Sep 16. PMID: 16169901; PMCID: PMC1236570
- MLL repression domain interacts with histone deacetylases; the polycomb group proteins HPC2 and BMI-1; and the corepressor C-terminal-binding protein Xia, ZB; Anderson, M; Diaz, MO; Zeleznik-Le, NJ Proceedings of the National Academy of Sciences U S A 2003 Jul 8;100(14):8342-7. doi: 10.1073/pnas.1436338100. Epub 2003 Jun 26. PMID: 12829790; PMCID: PMC166231
- Role for Id-1 in immunobiology of normal keratinocytes and in basal cell carcinoma Chaturvedi, V; Bonish, B; Bacon, P; Qin, JZ; Denning, MF; Foreman, K; Diaz, MO; Robinson, J; Nickoloff, BJ Experimental Dermatology 2003 Jun;12(3):255-60. doi: 10.1034/j.1600-0625.2003.00066.x. PMID: 12823438
- Role of INK4a/Arf locus-encoded senescent checkpoints activated in normal and psoriatic keratinocytes Chaturvedi, V; Cesnjaj, M; Bacon, P; Panella, J; Choubey, D; Diaz, MO; Nickoloff, BJ American Journal of Pathology 2003 Jan;162(1):161-70. doi: 10.1016/S0002-9440(10)63807-2. PMID: 12507899; PMCID: PMC1851109
- A new family of cyclophilins with an RNA recognition motif that interact with members of the trx/MLL protein family in Drosophila and human cells Anderson, M; Fair, K; Amero, S; Nelson, S; Harte, PJ; Diaz, MO Development Genes and Evolution 2002 Apr;212(3):107-13. doi: 10.1007/s00427-002-0213-8. Epub 2002 Mar 6. PMID: 11976948
Click below for a complete list of published works
Manuel Diaz Publications
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