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Phong T. Le, Ph.D.

Professor

Dept. of Microbiology and Immunology

and

Graduate Program Director

Cell Biology, Neurobiology and Anatomy

LeP.JPG (405709 bytes)

      B.S., Microbiology, 1980. Department of Microbiology, University of Illinois.
      M.S., Immunology, 1982. Department of Microbiology, Ohio State University.
      Ph.D., Immunology, 1985. Department of Microbiology, Ohio State University.
      Postdoctoral Fellow, National Research Service Award recipient, Department

      of Microbiology and Immunology, Duke University Medical Center.1985-1987
      Research Associate, Department of Microbiology and Immunology, Division  of  

      Rheumatology and Immunology, Duke University Medical Center. 1987-1989.
      Medical Research Associate, Department of Medicine, Division of Rheumatology

      and Immunology, Duke University Medical Center. 1989-1991.

EMAIL

 

Current Interests

Thymic epithelial cell biology in T cell development: 1) Role of thymic epithelial cells in

 the control of lineage commitment of thymic precursors through regulation of expression

of transcription factors; 2) molecular mechanism of age-associated thymic involution.

Laboratory Focus

The thymus is a lymphoid-epithelial organ whose main function is to generate nave T cells

for the peripheral T cell pool; nevertheless, the production of nave T cells deteriorates with

age, a condition known as thymic involution. Our laboratory is interested in understanding

 the molecular mechanisms by which thymic epithelial cells (TEC) affect T cell development
 in the normal setting and in the context of the aged thymus. We hypothesize that

TEC-T cell progenitor interaction orchestrates the coordinated expression of a combinatory

 set of transcription factors that affect progenitors lineage commitment and differentiation.

Aging in the thymus is affected by the changes at the apex of TEC-T cell progenitor

 interaction resulting in the decline in thymopoiesis. Thus, the critical steps toward

understanding the mechanism of aging in the thymus are to identify these changes in

molecular terms and then to determine whether these alterations lead to a decline in nave

T cell output.

 

Based on our observation that expression of the TEC specific the transcription factor

FoxN1, which is essential for functional maturation of TEC, is significantly reduced with

age, we have generated transgenic mice that overexpress FoxN1. These mice show the

absence of several age-associated changes in thymic involution such as reduced nave

T cell output, number of T cell progenitors and T cell precursor. The mouse model

provides us a novel animal model to discover the molecular mechanism that affects

thymic involution.

Publications

Le, P. T., K. L. Adams, N. Zaya, H. L. Mathews, W. J. Storkus, and T. M. Ellis.

 Human thymic epithelial cells inhibit IL-15- and IL-2-driven differentiation of NK cells

from the early human thymic progenitors. J. Immunol. 166:2194-2201, 2001.

Ortman, C. L., K. A. Dittmar, P. L. Witte, and P. T. Le. . Molecular characterization

of the mouse involuted thymus: aberrations in expression of transcription regulators in

thymocyte and epithelial compartments. Int. Immunol. 14:813-822, 2002.

Sempowski, G. D., M. E. Gooding, H. X. Liao, P. T. Le, and B. F. Haynes. T cell receptor delta excision circle assessment of thymic output in aging mice. Mol. Immunol.

38:841-848, 2002.

 

 

Last Reviewed: December  2008

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