About the Lab

About the Lab

NK cells are critical for the control of viral infection and malignancy. In rare cases, immunodeficiency results when NK cells or specific NK cell subsets are missing. In addition, NK cells hold tremendous promise in the field of immunotherapy. Despite their clinical importance, the molecular signals that drive human NK cell development are poorly understood. The focus of research in the Mace lab is to understand the molecular signaling that drives human NK cell development and how this is dysregulated in cases of human disease. In particular, signaling from the microenvironment that can support NK cell development in tissue is difficult to interrogate but holds important clues to the lineage restriction and homeostasis of NK cells.

NK cells exert effector function through the formation of an immunological synapse, a highly organized signaling platform formed between two cells. In a lytic synapse, the target is a virally infected or tumorigenic cell, however synapses may also be formed with other accessory cells. Identifying the contacts formed between NK cells and developmentally supportive stromal cells suggests the presence of a developmental synapse that integrates signals required for development. Through the use of non-diffraction limited microscopy (particularly stimulated emission depletion microscopy, STED) and other quantitative imaging and image analysis techniques (such as confocal microscopy and imaging flow cytometry, IFC), we can gain tremendous insight into the molecular events that drive immune cell formation and function.

We gain further insight into the signals that drive human NK cell development through the identification of genetic causes of NK cell deficiency. Through our collaboration with Baylor-Hopkins Center for Mendelian Genomics and the NK Evaluation and Research (NEAR) Clinic, we strive to identify the molecular basis of disease in patients with immunodeficiency affecting NK cell development or function. This has led to the discovery of previously unknown requirements for NK cell maturation and launched both basic and translational research into proteins such as the transcription factor GATA2, a leading cause of myelodysplastic syndrome in young adults and a critical regulator of NK cell development.