H. Daniel Lacorazza, Ph.D.
Departments of Pathology and Immunology
Research Member, The Dan Duncan Cancer Center
Faculty, Translational Biology and Molecular Medicine
Associate Member, Texas Gulf Coast Digestive Disease Center (DDC)
- B.Sc. and M.Sc. University of Buenos Aires, Argentina
- Ph.D. University of Buenos Aires, Argentina
- Fogarty Fellow, National Institutes of Health
- Research Fellow, Memorial Sloan-Kettering Cancer Center (Immunology Program)
- Senior Research Scientist, Memorial Sloan-Kettering Cancer Center (Molecular Pharmacology Program)
Billions of blood cells are produced every day from a relatively small subset of multipotent and undifferentiated cells: the hematopoietic stem cells (HSC). Bone marrow HSCs persist in a reversible non-proliferative state and yet produce enough lymphoid and myeloid progenitor cells to fulfill daily demands. Thus, a delicate balance between quiescence and proliferation ensures longevity of hematopoietic stem cells and an adequate production of blood cells. This equilibrium depends on a temporal expression of specific genes, which is modulated by transcription activators and repressors. There are emerging evidences indicating a differential control of proliferation in homeostatic and regenerative hematopoiesis. A handful of genes have been reported to control stem cell’s release from their quiescent state (i.e. PTEN, p21, ELF4, GATA2, Gfi1) providing therapeutic targets to treat stem cell leukemias and to lessen the deleterious effects of chemotherapy and radiation.
My group studies the molecular events that control hematopoiesis and development of the immune system and the crosstalk between immune cells and bone marrow hematopoiesis. We previously described that the transcription factor ELF4 regulates the innate immune system (Immunity, 2002: 17: 437-449) and modulates the quiescence of hematopoietic stem cells during homeostasis but not during regenerative hematopoiesis (Cancer Cell, 2006: 9,175-187). Therefore, modulation of ELF4 expression could potentially be used to induce proliferation of leukemic stem cells or to preserve quiescence during chemotherapy or bone marrow transplantation. We are currently extending our study to other non-proliferative cells, such as T-lymphocytes, and developing loss-of-function mouse models of tumor suppressors to study their role in the development and function of blood cells.
- Yao, JJ, Liu, Y., Lacorazza, H.D., Soslow, R.A., Scandura, J.M., Nimer, S.D., Hedvat, C.V. Tumor promoting properties of the ETS protein MEF in ovarian cancer. Oncogene (2007) 26: 4032-4037.
- Lacorazza, H.D., Yamada, T., Liu, Y., Miyata, Y., Sivina, M., Nunes, J., and *Nimer, S. The transcription factor MEF (ELF4) regulates the quiescence of primitive hematopoietic cells. Cancer Cell (2006) 9, 175-187. Featured Article on the Cover. *Co-corresponding authors
- Garcia-Barros, M., Lacorazza, H.D., Petrie, H., Haimovitz-Friedman, A., Cardon-Cardo, C., Nimer, S., Fuks, Z., Kolesnick, R. Host acid sphingomyelinase regulates microvascular function not tumor immunity. Cancer Research (2004) 64(22): 8285-8291.
- Lacorazza, H.D. and Nikolic-Zugic, J. (2004). Mechanism of Exclusion and Inclusion of TCRα Proteins during T-cell Development in TCR-transgenic and normal mice. J. Immunol. 173 (9): 5591-5600.
- Lacorazza, H.D., Miyazaki, Y., Di Cristofano, A., Deblasio, T., Hedvat, C., Cordon-Cardo, C., Mao, S., Zhang, J., Pandolfi, P.P., and Nimer, S.D. (2002). The ETS Protein MEF Plays a Critical Role in Perforin Gene Expression and the Development of Natural Killer Cells and NK-T Cells. Immunity. 17: 437-449. Featured article on the Cover.
- Aifantis I, Borowski C, Gounari F, Lacorazza HD, Nikolich-Zugich J, von Boehmer H. (2002). A critical role for the cytoplasmic tail of pTalpha in T lymphocyte development. Nature Immunol. 3(5): 483-8.
- Lacorazza, H.D., Porritt, H., and Nikolic-Zugic, J. (2001). Dysregulated expression of preTα reveals the opposite effects of pre-TCR at successive stages of T cell development. J. Immunol. 167:5689-5696.
- Lacorazza, H.D., Flax, J., Snyder, E., and Jendoubi, M. (1996). Expression of human β-hexosaminidase α-subunit gene in mouse brains upon engraftment of transduced progenitor cells. Nature Medicine, 2 (4), 424-429