Molecular Studies of Cellular Cytotoxicity

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

The overarching goal of this research program is the investigation of the innate immune system with a primary focus on natural killer (NK) cells and their use in the treatment of cancer. Our group has been a globally recognized leader in the study of the regulation of class I major histocompatibility complex (MHC) receptors in mouse (Ly49) and human (KIR) NK cells for many years, and we are pioneers in the identification of molecular mechanisms underlying the variegated expression of these receptors by NK cells. We have discovered many instances of genetic variation in KIR and Ly49 genes that can change the responsiveness of NK cells to MHC on target cells. In the past year, significant progress has been made in our investigation of the role of promoter competition in the variegated expression of KIR genes as well as lineage-determining transcription factors. We have demonstrated that competing promoters in the hematopoietic transcription factors GATA1 and GATA2 control cell fate determination. This discovery is expected to lead to the development of techniques to modulate cell fate determination. Our group also participates in multiple collaborative projects with intramural and extramural laboratories, as demonstrated by publications with groups at the University of Washington, Washington University at St Louis, and the NCI Center for Cancer Research in the past year.