Richie, Ellen R.

Richie, Ellen R. Ph.D.

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Research Interests

Thymus organogenesis, T cell development, thymic lymphoma

Current Research

My research program involves elucidating the molecular pathways that are involved in development of the thymus, the central organ in which T cell differentiation occurs. We are interested in the inductive interactions among hematopoietic cells, neural crest cells, and epithelial cells that are essential for generating the fetal thymus rudiment and for sustaining the thymus during adult life. T cell development is not a cell autonomous process, but rather requires thymic epithelial cell-derived signals that promote thymocyte survival, proliferation and differentiation. A major aspect of our work is to elucidate the functions and lineage relationships of distinct thymic epithelial subsets that are localized within different microenvironmental zones of the thymus.

Since T cell output from the thymus is essential to maintain a protective naïve peripheral T cell pool, we are also interested in understanding the process of thymus involution that occurs during the aging process or as a result of cytoablative therapy or severe viral infection. Thymus involution is associated with reduced T cell output and increased susceptibility to infectious disease and perhaps cancer. We have demonstrated that expression of a cyclin D1 transgene targeted to thymic epithelial progenitors by a keratin 5 promoter prevents thymus involution. A primary goal is to decipher the molecular mechanism(s) by which enforced cyclin D1 expression in TEC progenitors prevents thymus involution in order to develop a rationale basis for future therapeutic strategies.

We are also interested in aberrant molecular pathways that result in thymic lymphoma development. Our experimental model is a murine thymic lymphoma induced by injection of the carcinogen N-methyl-N-nitrosurea (MNU). We have shown that the AKR/J strain is more susceptible to MNU-induced lymphomagenesis than other common inbred strains. Using molecular and genetic analyses, we found that the enhanced susceptibility of AKR/J mice cannot be explained by somatically acquired integrations of the endogenous recombinant murine leukemia viruses that are characteristically associated with spontaneous lymphomas in older mice of this strain. Instead, nonviral genes in the AKR/J background are responsible for enhanced lymphoma susceptibility to the carcinogen MNU. We demonstrated the presence of a novel lymphoma susceptibility gene on chromosome 7. This finding led to the analysis of mice containing mutations in various candidate genes, including eed, an essential transcriptional repressor that functions during embryogenesis to regulate anterior-posterior patterning. Our data indicate that, in the adult, eed plays an important role in regulating the progression of MNU-induced lymphoma. Current studies focus on identifying the molecular mechanisms by which eed acts as a tumor susceptibility gene in regulating lymphoma development.

Selected Publications

  1. Lomada D, Liu B, Coghlan L, Hu Y, Richie ER. Thymus medulla formation and central tolerance are restored in IKKalpha-/- mice that express an IKKalpha transgene in keratin 5+ thymic epithelial cells, J Immunol, 178 (2), 829-37, 2007
  2. Nowell CS, Richie E, Manley NR, Blackburn CC, Thymus and parathyroid organogenesis, in Principles of Tissue Engineering, edited by Lanza R, Langer R, Vacanti JP, Elsevier/Academic Press, Burlington, MA, 647-62, 2007
  3. Zamisch M, Moore-Scott B, Su DM, Lucas PJ, Manley N, Richie ER. Ontogeny and regulation of IL-7 expressing thymic epithelial cells, J Immunol, 174 (1), 60-7, 2005
  4. Klug DB, Carter C, Gimenez-Conti IB, Richie ER. Cutting edge: thymocyte-independent and thymocyte-dependent phases of epithelial patterning in the fetal thymus, J Immunol, 169 (6), 2842-5, 2002
  5. Richie ER, Schumacher A, Angel JM, Holloway M, Rinchik EM, Magnuson T. The Polycomb-group gene eed regulates thymocyte differentiation and suppresses the development of carcinogen-induced T-cell lymphomas, Oncogene, 21 (2), 299-306, 2002

Contact Information


Mailing Address: P.O. Box 389, Smithville, Texas 78957
Physical Address: 1808 Park Road 1C, Smithville, Texas 78957
Phone: (512) 237-9435