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Microbiology and Immunology
Stritch School of Medicine
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Phong T. Le, PhD

Professor

Microbiology & Immunology

    Research Interests:

    • Biology of human thymic epithelial cells (TECs)

Education

Ph.D., Microbiology, Ohio State University

 

Research Interests

My laboratory studies the biology of human thymic epithelial cells (TECs) in the developmental process of T cells from hematopoietic stem cells (HSCs), particularly HSCs from human umbilical cord blood. We interrogate the development of human T cells in vitro by establishing TEC lines from pediatric human thymus. These TEC lines are then genetically modified to identify critical genes that support T cell development from the CD34pos HSCs.

We have generated human TEC lines that overexpress the Notch ligand Delta-like 4 (TEC-DLL4), the physiological ligand for the Notch receptor; Notch signaling is essential for initiating T-lineage commitment in HSCs and promotes their development into mature T-cells. Other molecules being studied are WNT3A and two critical components of the thymoproteasome, PSMB8 and PSMB11; both are involved in the generation of thymic-specific peptides for the generation of mature CD4 and CD8 T-cells through the positive selection process.

Lastly, a cell-free system established with exosomes from the established TEC-DLL4 lines is being investigated as an off-the-shelf “drug” to promote HSCs to develop into T-cells. Our work has a significant impact on developing T-cells with anti-tumor activity for cell-based immunotherapy and ameliorating T cell engraftment in patients receiving HSC transplant as a treatment for hematopoietic malignancies.

Publications/Research Listings

Schnittman, S.M., K.H. Singer, J.J. Greenhouse, S.K. Stanley, L.P. Whichard, P.T. Le, B.F. Haynes, and A.S. Fauci. 1991. The thymic microenvironment induces HIV expression. Physiologic secretion of IL6 by thymic epithelial cells up-regulates virus expression in chronically infected cells. J. Immunol. 147:2523-8.

Le, P.T., S. Lazorick, L.P. Whichard, B.F. Haynes and K.H. Singer. 1991. EGF and TGF-αregulate mRNA levels of IL1-α and IL6 in human thymic epithelial (TE) cells at a post-transcriptional level. J. Exp. Med. 174:1147-57

Sempowski, G.D., M.E. Gooding, H.X. Liao, P.T. Le, B.F. Haynes. 2002. T cell receptor delta excision circle assessment of thymic output in aging mice. Mol. Immunol. 38:841-48.

Ortman CL, Dittmar KA, Witte PL, P.T. Le. 2002. Molecular characterization of the mouse involuted thymus: aberrations in the expression of transcription regulators in thymocyte and epithelial compartments. Int Immunol. 14:813-22.

Beaudette-Zlatanova BC, Knight KL, Zhang S, Stiff PJ, Zúñiga-Pflücker JC, Le PT. 2011. A human thymic epithelial cell culture system for the promotion of lymphopoiesis from hematopoietic stem cells. Exp. Hematol. 39: 570-9.

Zook, E.C., Krishack, P.A., Zhang, S., Zeleznik-Le, N.J., Firulli, A., Witte, P.L., and Le, P.T. Overexpression of Foxn1 attenuates age-associated thymic Involution and prevents the expansion of peripheral CD4 memory T cells. Blood. 2011 September 9

Beaudette-Zlatanova BC, Le PT, Knight KL, Zhang S, Zakrzewski S, Parthasarathy M, Stiff PJ.  2012. A potential role for B cells in suppressed immune responses in cord blood transplant recipients. Bone Marrow Transplant, 48(1): 85-93

Erin C. Zook, Shubin Zhang, Rachel M Gerstein, Pamela L. Witte, and Phong T. Le. 2013. Enhancing T lineage production in aged mice:  a novel function of Foxn1 in the bone marrow. J. Immunology. 191(11): 5583-93.

Le, PT, Pearce MM, Zhang S, Campbell EM, Fok CS, Mueller ER, Brincat CA, Wolfe AJ, Brubaker L. 2014. IL22 regulates human urothelial cell sensory and innate functions through modulation of acetylcholine response, immunoregulatory cytokines, and antimicrobial peptides: Assessment of an in vitro model. PLoS One, 9: e11375-, 1-12.

Cynthia Perez, Lourdes Plaza-Rojas, Elena Kostenko, Kushal Prajapati, Brianna Burke, Michael Delos Reyes, Anna Austin, Shubin Zhang, Phong Le, and Jose Alejandro Guevara-Patino. 2024. Natural Killer Group 2D (NKG2D) receptor signaling shapes T cell thymic education. J Leukocyte Biology, 115: 306-321.

Olga Kalinina, Lisa M. Minter, Anne I. Sperling, Maile K. Hollinger, Phong Le, Barbara A. Osborne, Shubin Zhang, Patrick Stiff, Katherine L. Knight. 2024. Exopolysaccharide-treated dendritic Cells Effectively Ameliorate Acute Graft-versus-Host Disease. Transplant Cellular Therapy, 1: 79e1-79e10.