Research

Research

The Le Laboratory is composed of a core group of talented research scientists, postdoctoral fellows, students and research associates. Our work bridges the fields of Cancer Biology, Developmental Biology, and Stem Cell Biology that focuses on neural-crest derived tissue development, regeneration, and tumorigenesis, in particular, the biology of neurofibromatosis, a group of genetic disorders that causes tumors to form on nerve tissue.

Our broad research goals are to 1) decipher mechanisms that initiate and drive human cancer, 2) generate robust in vivo and in vitro models to delineate tumor progression and 3) develop novel therapeutic targets for human cancers. A related goal is to translate our basic scientific discoveries in the laboratory into human clinical trials. Our primary scientific interests include identifying the cell of origin of tumorigenesis and elucidating the roles of tumor microenvironment in cancer development. Our laboratory dissects these cellular and molecular mechanisms of tumorigenesis from the developmental perspective. We utilize Neurofibromatosis Type 1, a common tumor predisposition human genetic disorder, as a model to address these two fundamental questions in Cancer Biology as well as elucidating cutaneous nervous system development and regeneration.

Neurofibromatosis Type 1

A major contribution of our laboratory is the generation and exploitation of novel neurofibromatosis models to elucidate mechanisms that initiate neurofibroma, a Schwann cell tumor, development and drive their malignant transformation. Our work has identified the cells of origin for different types of neurofibroma [Cancer Cell 26(5): 695-706; Cell Stem Cell 4(5):453-63], defined developmental “window-of-opportunity” within Schwann cell lineage for neurofibroma development [Cancer Research 71(13):4686-95]; and delineated vital cancer pathways for its malignant transformation into Malignant Peripheral Nerve Sheath Tumors, which account for 10% of all soft tissue sarcomas, and are lethal cancers whose pathways of activation are poorly understood. [Cell, 152(5): 1077-1090; Cell Reports, 6(1): 81-92; Cancer Research, 74(2): 586-97]. These and current studies in our laboratory address fundamental, unanswered questions in the neurofibromatosis field. They will not only provide important insights into the molecular and cellular pathogenesis of neurofibromatosis but also could lead directly to novel and potentially effective therapies aimed at delaying or preventing tumor formation in neurofibromatosis patients, where none exist today.

Clinically, the neurofibromatosis program at UT Southwestern Medical Center is the primary neurofibromatosis clinic to provide specialized, comprehensive medical care for neurofibromatosis patients in North Texas and surrounding areas. Dr. Le serves as the co-director and attending physician of this clinic. This neurofibromatosis clinic also provides a platform for development and implementation of clinical trials, patient registry and tissue bank with the goal of developing more effective guidelines for neurofibromatosis clinical care as well as advancement of scientific research in the neurofibromatosis field.

In addition, it was this work in neurofibromatosis and mechanisms whereby neural-crest derived tissues and nerves can affect tumor development in skin and other tissues that serendipitously lead us to uncover the identity of follicular epithelial cells that directly give rise to hair and mechanisms that cause hair to turn gray [Genes & Development. 31(8): 744-756] – findings that could one day help identify possible treatments for balding and hair graying.