Michael G. Brown, PhD
NK cells and their receptors in immunity to cytomegalovirus infection
The Brown laboratory uses tools of molecular genetics, biochemistry and cellular immunology to identify and characterize genes and their protein products that regulate the functions of natural killer (NK) cells. NK cells are well known for their capacity to recognize and destroy cancer cells. Cancer cells display proteins that are not typically expressed by non-cancer cells, including MHC class I-related proteins that serve as ligands of NKG2D stimulatory receptors that are found on NK cells. However, unlike other lymphocytes, NK cells actually express a variety of receptors that either inhibit or stimulate their production and release of cytokines and their potential for killing cancer cells or virus infected cells. Thus, a major focus of this research is on understanding how NK cells actually recognize their targets at the molecular level. Previous findings of the lab include identification of the Ly49H NK cell activation receptor as a critical component of the NK cell arsenal required in direct recognition of virus infected cells and in stimulating NK cells sufficiently to kill the infected targets. Recent work in the lab has also shown that Ly49H-independent mechanisms are vital in recognition and control of acute virus infections.
The lab designed and developed a high-throughput molecular genetic screening strategy to efficiently and reliably identify genes associated with innate NK cell recognition and control of virus levels in acute virus infections. Two independent screens are underway in different genetic settings with differing contributions through NK cells to identify various NK cell proteins and other innate immune response proteins associated with host defenses in infectious diseases. Collaborations with Dr. S.M. Fu and Dr. S.T. Ju have been established to use similar molecular genetics strategies to identify genes associated with altered immune responses and autoimmune diseases in mice. Their studies have utilized the services of the hybridoma core, the FACS core, the tissue procurement core and most recently the research histology core.