Biological Research | Institute of Gerontology

Drs. Gafni and Steel's focus is on enzyme structure and function and the role of protein misfolding and aggregation into amyloid in age-associated diseases such as Alzheimers and non-insulin-dependent diabetes. Research by Dr. Gafni's laboratory focuses on the highly specific molecular interactions that lead to amyloid formation and the forces that stabilize this complex structure. Advanced biophysical methodologies such as laser spectroscopy play a critical role in their work. Work in this laboratory has included the development of laser-based spectrometer for measuring the room-temperature tryptophan phosphorescence from proteins in solution in real time. Using this measure of the state of the core of alkaline phosphatase, Drs. Steel and Gafni have studied the unfolding and refolding of alkaline phosphatase.

Research dealing with vital processes of the endoplasmic reticulum (ER), which correctly folds and modifies nascent polypeptides into functional proteins destined for secretion is being conducted by Dr. Gaut. Insulin, growth hormone, blood clotting factors and many other proteins have great health and pharmaceutical importance, but first must be correctly folded within the lumen of the ER.

Dr. Guan's research focuses on the roles of protein phosphorylation in cellular regulation. Protein phosporylation is the mechanism cells use most to regulate cell division, growth, and differentiation. One primary area of investigation by Dr. Guan is to understand the molecular mechanism of protein kinase activation. MAP kinase activity is determined using in vitro cultured cells as a model.

Drs. Miller and Burke's research is on heterogeneity among T lymphocytes, including genetic influences on lifespan, T cell function, and disease. Dr. Miller's studies have shown that aging leads to an increase in the proportion of T lymphocytes of the memory subset, and that the accumulation of memory T cells largely accounts for the age-dependent loss of IL-2 (interleukin-2) production and responsiveness to IL-2. Dr. Burke is studying the genetic basis for normal mammalian aging using the laboratory mouse as a model system. Because many genes lose normal regulated expression during mammalian aging, one research program in the laboratory seeks to understand the fundamental genetic mechanisms involved in stabilizing post-pubertal gene expression.

Work is being conducted by Dr. Keller to show the expression of a variety of genes, such as cytokines, oncogenes, etc. is either increased or decreased with aging. His team is attempting to define the mechanisms through which aging modulates gene expression. He is also examining why prostate cancer targets bone and how it promotes osteoblastic lesions.

Drs. Ashton-Miller, Goldstein, Gross, and Hunt's research characterizes how aging affects mobility, human movement and balance; bone and connective tissue fragility; the morphologic, architectural, mechanical and remodeling properties of bone. Combining molecular genetics and biomechanics, they have been able to characterize the functional contribution of a variety of extracellular matrix proteins of bone, suggesting strategies for treatment of skeletal fragility. Dr. Ashton-Miller uses biomechanical experiments and computer simulations to study the effects of aging on the human musculoskeletal system. He studies the physical and cognitive factors responsible for failure to detect and avoid hazards that can cause slips, trips and falls, especially in physically risky tasks such as walking on an icy sidewalk or rising from a chair. He is also studying the biomechanical factors that can adversely affect the ability of even healthy elderly to safely arrest a fall. Dr. Hunt is studying the physical and mechanical properties of the molecular motors that underlie biologic motility, particularly as it pertains to the movements of chromosomes during mitosis.

Drs. Brooks, Carlson, Faulkner, and Kuzon in the Muscle Mechanics Laboratory focus on the mechanical properties of whole skeletal muscles, motor units and single fibers for the determination of the mechanisms underlying atrophy and weakness in muscles of old animals. One long-term goal of this group is to reduce functional deficits, to understand the (large) age effects on magnitude of injury, rate of recovery, and plateau of recovery, and more generally, to determine the mechanisms responsible for the 20% to 30% loss in the development of maximum force in the muscles of aged animals. Studies also focus on mammalian muscle regeneration, denervation/reinnervation of muscle fibers, and mechanical dysfunction of skeletal muscle as a result of congenital anomalies, and direct muscle injury. These investigators are involved in the development of new technologies and instrumentation for research of skeletal muscle culture, contraction-induced injury and aging.