Research Interests:

Work in the Miller lab centers on the genetics and cell biology of aging in mice, with emphasis on the immune system. Major ongoing projects include studies of:

Aging and T lymphocyte activation, with particular emphasis on protein kinases and cytoskeletal pathways in the first few minutes after encounter with antigen. Confocal microscopy is used to evaluate responses of individual T cells and T cell subsets. The most recent work involves modification of the T cell surface glycoproteins to improve function of T cells from old mice.

Genetics of aging: Several related projects are underway to learn more about the way in which inherited alleles influence T cell function, aging, and late-life disease. A gene mapping project, in collaboration with Dr. David Burke in Human Genetics, aims at identifying loci that influence aging rate, disease susceptibility, and immune parameters in segregating mouse populations. A second initiative aims to develop new mouse lines, starting from wild- trapped progenitors, that may exhibit delayed aging and increased stress resistance.

Gene expression analysis of aging. The lab uses array-based methods for analysis of gene expression to study several mouse models of decelerated aging, including studies of dwarf mice, wild-derived mouse stocks, and mice on low-methionine diets. Studies of the effects of aging on T cell gene expression in humans and baboons are also under way.

Aging and stress at the cellular level. Recent work has shown that long-lived mutant mice have stress-resistant cells, and is now focusing in on the molecular changes that mediate stress resistance and the effect of stress resistant cells in determining aging and disease risk.

Brief Biography

Dr. Miller received his MD and PhD (in Human Genetics) at Yale University in 1976-77, undertook postdoctoral training at Harvard and Sloan-Kettering, and was on the Pathology Department faculty at Boston University from 1982-1990 before he moved to the University of Michigan. Dr. Miller's research work focuses on the effects of aging on T cell subset interactions and on the ways in which aging alters the earliest phases of the T cell activation process. Newer work in the laboratory deals with the genetics of lifespan and the development of new animal models for delayed aging. Dr. Miller also serves as Associate Director for Research in the Geriatrics Center, and is a Research Scientist at the Ann Arbor VA Medical Center. He is the recipient of the 1994 AlliedSignal Award for Research in Aging and the 1997 Robert W. Kleemeier Award for Research in Aging.