Scientist profiles A-F
Sunnybrook Health Sciences Centre
2075 Bayview Ave., Room A3 40
- B.Sc., 1989, biology, Eckerd College, U.S.
- PhD, 1994, biochemistry and molecular biology, University of South Florida, U.S.
Appointments and Affiliations:
- Senior scientist, Biological Sciences, Odette Cancer Research Program, Sunnybrook Research Institute
- Assistant professor, immunology, University of Toronto
- Transcriptional regulation of T cell development
Our research is aimed at understanding the role of transcription factors in T cell development.
T cells develop from hematopoietic stem cells, which initially can become any of the eight major blood cell types. As this process begins, new genes are expressed, and the expression of these genes is directed by transcription factors. We are focusing on two families of transcription factors that are involved in these processes, the Ets and basic helix-loop-helix families.
We have identified several members of these families that are active during early T cell development. To study the roles these factors play, we are disrupting or enhancing their activities in hematopoietic stem cells using retroviral gene transfer. We then monitor the effects of these perturbations on fate choice, differentiation, cell growth and cell death as the stem cells develop into T cells.
We have found that one transcription factor, HEB, can be expressed in different forms that in turn have different effects on cell growth. We believe that the ratios of these factors in developing T cells could be critical in determining if T cells are programmed with the necessary growth control responses that protect them from overgrowth and that could result in cancerous transformation, but that permit proliferation in response to infection. Studies are underway to understand the molecular interactions among these transcription factors, their target genes and the other cellular machinery that controls the normal and aberrant development of T cells.
Ultimately, it is in these networks of interactions that the answers will be found to provide an understanding of the genetic programs that are installed during T cell development and that allow their unique and essential immune functions to be deployed while avoiding malfunctions that can lead to leukemia, lymphoma or autoimmune disease.
- Anderson MK, Pant R, Miracle AL, Sun X, Luer CA, Walsh CJ, Telfer JC, Litman GW and Rothenberg EV. Evolutionary origins of lymphocytes: ensembles of T-cell and B-cell transcriptional regulators in a cartilaginous fish. J Immunol. 2004 May 15;172(10):5851–60.
- Telfer JC, Hedblom EE, Anderson MK, Laurent MN and Rothenberg EV. Localization of the domains in runx transcription factors required for the repression of CD4 in thymocytes. J Immunol. 2004 Apr 1;172(7):4359–70
- Hernández-Hoyos G, Anderson MK, Wang C, Rothenberg EV and Alberola-Ila J. GATA-3 expression is controlled by TCR signals and regulates CD4/CD8 differentiation. Immunity. 2003 Jul;19(1):83–94.
- Anderson MK, Hernandez-Hoyos G, Dionne CJ, Arias AM, Chen D and Rothenberg EV. Definition of regulatory network elements for T-cell development by perturbation analysis with PU.1 and GATA-3. Dev Biol. 2002 Jun 1;246(1):103–21.
- Anderson MK, Weiss A, Hernandez-Hoyos G and Rothenberg EV. Constitutive expression of PU.1 in fetal hematopoietic progenitors blocks T cell development at the pro-T cell stage. Immunity. 2002 Feb;16(2):285–96.
Related News and Stories:
- Scientists score high with operating funds: CIHR invests in eight researchers in its latest competition (May 30, 2012)
- T Cell Fundamentals: Sunnybrook biologist’s research is laying the groundwork for future trials in immunity to cancer and other diseases (June 18, 2007)