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RESEARCH FOCUS AREAS:
- T-cell development
- Thymic epithelial cell biology
- Exosomes
My laboratory studies the biology of human thymic epithelial cells (TECs) in the developmental process of T-cells from hematopoietic stem cells (HSCs). We interrogate human T cell development 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, 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 TEC 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.
EDUCATION:
- PhD, The Ohio State University
- Postdoctoral fellowship, Duke University
SELECT PUBLICATIONS:
- IL22 regulates human urothelial cell sensory and innate functions through modulation of the acetylcholine response; immunoregulatory cytokines and antimicrobial peptides: assessment of an in vitro model Le, PT; Pearce, MM; Zhang, S; Campbell, EM; Fok, CS; Mueller, ER; Brincat, CA; Wolfe, AJ; Brubaker, L PLoS One 2014 Oct 29;9(10):e111375. doi: 10.1371/journal.pone.0111375. PMID: 25354343; PMCID: PMC4213028
- Enhancing T lineage production in aged mice: a novel function of Foxn1 in the bone marrow niche Zook, EC; Zhang, S; Gerstein, RM; Witte, PL; Le, PT Journal of Immunology 2013 Dec 1;191(11):5583-93. doi: 10.4049/jimmunol.1202278. Epub 2013 Nov 1. PMID: 24184560; PMCID: PMC4081451
- Overexpression of Foxn1 attenuates age-associated thymic involution and prevents the expansion of peripheral CD4 memory T cells Zook, EC; Krishack, PA; Zhang, S; Zeleznik-Le, NJ; Firulli, AB; Witte, PL; Le, PT Blood 2011 Nov 24;118(22):5723-31. doi: 10.1182/blood-2011-03-342097. Epub 2011 Sep 9. PMID: 21908422; PMCID: PMC3228493
- Mixed lineage kinase 3 modulates β-catenin signaling in cancer cells Thylur, RP; Senthivinayagam, S; Campbell, EM; Rangasamy, V; Thorenoor, N; Sondarva, G; Mehrotra, S; Mishra, P; Zook, E; Le, PT; Rana, A; Rana, B Journal of Biological Chemistry 2011 Oct 28;286(43):37470-82. doi: 10.1074/jbc.M111.298943. Epub 2011 Aug 31. PMID: 21880738; PMCID: PMC3199493
- A human thymic epithelial cell culture system for the promotion of lymphopoiesis from hematopoietic stem cells Beaudette-Zlatanova, BC; Knight, KL; Zhang, S; Stiff, PJ; Zúñiga-Pflücker, JC; Le, PT Experimental Hematology 2011 May;39(5):570-9. doi: 10.1016/j.exphem.2011.01.014. Epub 2011 Feb 4. PMID: 21296124; PMCID: PMC3402177
- In vitro requirement for periostin in B lymphopoiesis Siewe, BT; Kalis, SL; Le, PT; Witte, PL; Choi, S; Conway, SJ; Druschitz, L; Knight, KL Blood 2011 Apr 7;117(14):3770-9. doi: 10.1182/blood-2010-08-301119. Epub 2011 Feb 1. PMID: 21285437; PMCID: PMC3083296
- Migration of immature and mature B cells in the aged microenvironment Wols, HA; Johnson, KM; Ippolito, JA; Birjandi, SZ; Su, Y; Le, PT; Witte, PL Immunology 2010 Feb;129(2):278-90. doi: 10.1111/j.1365-2567.2009.03182.x. Epub 2009 Oct 21. PMID: 19845796; PMCID: PMC2814469
- The effects of microenvironment and internal programming on plasma cell survival Minges Wols, HA; Ippolito, JA; Yu, Z; Palmer, JL; White, FA; Le, PT; Witte, PL International Immunology 2007 Jul;19(7):837-46. doi: 10.1093/intimm/dxm051. Epub 2007 Jul 2. PMID: 17606982
- Role of stromal cells and their products in protecting young and aged B-lineage precursors from dexamethasone-induced apoptosis Pifer, J; Stephan, RP; Lill-Elghanian, DA; Le, PT; Witte, PL Mechanisms of Ageing and Development 2003 Feb;124(2):207-18. doi: 10.1016/s0047-6374(02)00141-0. PMID: 12633941
- Molecular characterization of the mouse involuted thymus: aberrations in expression of transcription regulators in thymocyte and epithelial compartments Ortman, CL; Dittmar, KA; Witte, PL; Le, PT International Immunology 2002 Jul;14(7):813-22. doi: 10.1093/intimm/dxf042. PMID: 12096041
Click below for a complete list of published works
Phong Le Publications
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