Paul E. Love, M.D.,Ph.D.
Section on Hematopoiesis and Lymphocyte Biology
NIHBC 06B 2B210
Genes and Signals Regulating Mammalian Hematopoiesis
Our research focuses on the development of the mammalian hematopoietic system. Of particular interest is the characterization of signal transduction molecules and pathways that regulate T cell maturation in the thymus. Current projects include the generation of transgenic and conditional deletion mutants to evaluate the importance of T cell antigen receptor (TCR) signaling and TCR signaling subunits at specific stages of T cell development. We are also using gene profiling (RNA-seq and ChIP-seq) to identify and characterize molecules that are important for thymocyte selection, a process that promotes the survival and development of functional T cells and the death of auto-reactive T cells that could cause autoimmune disease. Further, we are analyzing the function of Themis and Fbxl12, two T cell–specific signaling proteins recently identified by our laboratory. Another area of investigation focuses on hematopoietic stem cells (HSCs). We have begun to characterize the genes that are important for the generation and maintenance of HSCs and for their differentiation into specific hematopoietic lineages. These studies have revealed a critical function for one protein (Ldb1) in controlling the self-renewal/differentiation cell-fate decision in hematopoietic stem cells and in the genesis of certain types of T cell acute lymphoblastic leukemia (T-ALL) in children.
Dr. Paul Love earned a B.S. degree in Biochemistry from Syracuse University and received an M.D. and Ph.D. in the MSTP program at the University of Rochester. He completed a residency program in Laboratory Medicine at Washington University, St. Louis and a fellowship in Human Genetics in NICHD, before conducting post-doctoral research in NICHD. He became an intramural Principal Investigator in 1993 and is now a tenured Senior Investigator and head of the Section on Hematopoiesis and Lymphocyte Biology in NICHD.
The research focus of Dr. Love’s lab is in the area of mammalian hematopoiesis. The lab has a long history of studying the process of T cell development, which begins with migration of multipotent progenitor cells, derived from hematopoietic stem cells in the bone marrow, to the thymus. Immature T cells then undergo a series of developmental steps in the thymus, including a process of selection that promotes the development of functional cells and the deletion of overtly self-reactive cells, ultimately leading to the generation of mature “self-tolerant” T lymphocytes that exit the thymus and populate the peripheral lymphoid organs. Dr. Love’s group has investigated questions relating to each of these steps in the T cell developmental pathway over the years; however, the main focus of his lab is the role and importance of signals transduced by the T cell antigen receptor (TCR) for T cell maturation. Current work includes studies aimed at understanding how TCR signaling influences susceptibility to autoimmune disease, how TCR signaling might be modified to assist in tumor immunotherapy, and investigating potential therapeutic interventions for the treatment of human hematopoietic stem cell or T cell malignancies.
Gaud G, Lesourne R, Love PE. Regulatory mechanisms in T cell receptor signalling. Nat Rev Immunol. 2018;18(8):485-497.
Hwang S, Palin AC, Li L, Song KD, Lee J, Herz J, Tubo N, Chu H, Pepper M, Lesourne R, Zvezdova E, Pinkhasov J, Jenkins MK, McGavern D, Love PE. TCR ITAM multiplicity is required for the generation of follicular helper T-cells. Nat Commun. 2015;6:6982.
Li L, Mitra A, Cui K, Zhao B, Choi S, Lee JY, Stamos DB, El-Khoury D, Warzecha C, Pfeifer K, Hardwick J, Zhao K, Venters B, Davé UP, Love PE. Ldb1 is required for Lmo2 oncogene-induced thymocyte self-renewal and T-cell acute lymphoblastic leukemia. Blood. 2020;135(25):2252-2265.
Zhao B, Yoganathan K, Li L, Lee JY, Zúñiga-Pflücker JC, Love PE. Notch and the pre-TCR coordinate thymocyte proliferation by induction of the SCF subunits Fbxl1 and Fbxl12. Nat Immunol. 2019;20(10):1381-1392.
Choi S, Warzecha C, Zvezdova E, Lee J, Argenty J, Lesourne R, Aravind L, Love PE. THEMIS enhances TCR signaling and enables positive selection by selective inhibition of the phosphatase SHP-1. Nat Immunol. 2017;18(4):433-441.
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This page was last updated on October 23rd, 2020