Richard A. Miller, M.D., Ph.D.
Professor of Pathology
millerr@umich.edu
Campus Address:
CCGCB, Room 5316
1500 East Medical Center Drive
Ann Arbor, Michigan 48109-0940
Phone: 734/936-2122
Annual Report | Biography | Research Interests | Selected Publications
Departmental Annual Report
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 Institute of Gerontology and 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.
Research Interests
Genetics of aging and immunity in mice.
Work in my lab centers on three topics: T lymphocyte activation, age-related
changes in T cell subsets, and the genetics of aging.
T lymphocyte activation: we study the earliest phase of T cell activation, with particular emphasis on aging and on differences between subsets of helper T cells. Ongoing projects includes studies of phosphorylation of the T cell receptor zeta chain, analysis of the activation of Raf-1 and signal transduction though ras, and studies of the causes and consequences of activation of JNK and ERK. New initiatives include studies of protein kinase C and LAT translocation to the site of T cell/APC interaction using confocal microscopy, and analysis of redistribution of signal proteins in cholesterol-rich membrane microdomains.
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. We are using 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.
Selected Publications
Eisenbraun, M. D., A. Tamir, and R. A. Miller.
2000. Altered composition of the immunological synapse in an anergic,
age-dependent memory T cell subset. J. Immunology 164:6105-6112.
Flurkey, K., J. Papaconstantinou, R. A. Miller, and D. E. Harrison. 2001. Life span extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production. Proc. Natl. Acad. Sci. USA 98:6736-6741.
Miller, R. A. 2001. Biomarkers of aging: prediction of longevity using age-sensitive T cell subset determinations in a middle-aged, genetically heterogeneous mouse population. J. Gerontol. Biol. Sci. 56A:B180-B186.
Garcia, G. G., and R. A. Miller. 2001. Single-cell analyses reveal two defects in peptide-specific activation of naïve T cells from aged mice. J. Immunol. 166:3151-3157.
Dozmorov, I., A. Bartke, and R. A. Miller. 2001. Array-based expression analysis of mouse liver genes: effect of age and of the longevity mutant Prop1df. J. Gerontol. Biol. Sci., 56A: B72-B80.