Charlie Lutz, Ph.D.

Professor

Selected publications

Research statement: Natural killer (NK) lymphocytes bridge the innate and adaptive immune system. NK cells recognize aberrant cells early in infection and tumor surveillance. NK cells kill aberrant cells and secrete cytokines to orchestrate subsequent adaptive immune responses. Unlike T and B lymphocytes, relatively little is known about how NK cells recognize “nonself.”

1. NK cell recognition of squamous cell carcinoma (SCC) cells. SCCs are the major cancers of the mouth and upper aerodigestive tract and are important cancers in many other organs. Little is know about how NK cells recognize epithelial cancers in general and SCCs in particular. We have shown that SCC cells stimulate NK cells via at least two types of molecules, one or more unidentified cell surface molecules and soluble interleukin 18. Both cell surface molecules and interleukin 18 are required to stimulate NK interferon gamma secretion. In contrast, cell surface molecules alone are sufficient to stimulate NK-mediated cytolysis. A major goal of the lab is to identify the SCC molecules that stimulate NK cells and how they collaborate with interleukin 18 signals to stimulate interferon gamma secretion.

SCCs express MICA and MICB, molecules that stimulate both NK cells and T cells. A related goal of the lab is to investigate how MICA and MICB gene expression is controlled. We are particularly interested in how viruses and therapeutic agents regulate MICA and MICB and immune recognition.

2. Regulation of KIR gene expression. NK cells use killer immunoglobulin like receptors (KIR) to recognize aberrant cells. KIR bind to MHC class I molecules, which are downregulated on cancer and infected cells. Because most KIR are inhibitory receptors, they protect normal MHC class I high cells from NK attack. KIR expression is quite unusual and may reveal unique gene control mechanisms. KIR genes are expressed in a random fashion by NK cells. We showed that KIR gene expression is also allele specific; individual NK cells may express either maternal, paternal, both, or neither allele of any particular KIR gene. We also showed that allele specific KIR expression is controlled by promoter DNA methylation. Our next objective is to investigate the molecular mechanisms by which KIR gene methylation inhibits transcription. We also are investigating how KIR expression is established in NK cell maturation.

3. Effects of aging on NK cell function. Immune function declines with normal aging in humans and laboratory animals. We found that elderly individuals have more CD94 positive NK cells than do young adults. We will investigate the causes and consequences of elevated CD94 expression.