The Waddell Lab

My research interests are concerned with the molecular mechanisms of aging and in particular on a phenomenon called sarcopenia. Sacropenia is the gradual deterioration of skeletal muscle that accompanies the aging process and is a serious medical condition facing millions of elderly people. The sarcopenic muscle shows signs of atrophy as well as a reduced capacity to regenerate following damage. Muscle loss or atrophy occurs as the result of a number of different conditions including disuse, cachexia, inflammation, exposure to corticosteroids and aging. A number of studies aimed at identifying differentially expressed genes in atrophy and aging models have found a number of interesting genes, including the E3Ubiquitin Ligase, MuRF1, which is expressed predominantly in skeletal muscle and is up-regulated in virtually all atrophy models. In addition to MuRF1, HDAC4, a class II Histone Deacetylase, is rapidly and significantly up-regulated only under neuromuscular damage-induced skeletal muscle atrophy. Furthermore, a targeted disruption of the MuRF1 gene in mice leads to a resistance in muscle wasting under atrophic conditions. These observations, among others, have led to the hypothesis that these genes may play a pivotal role in regulating a suite of other genes important in general skeletal muscle physiology, including the processes of sarcopenia and cellular stress handling. With this hypothesis in mind, my research is focused on understanding the molecular and genetic controls of longevity and the role that cellular stress may play in aging. In particular, I am interested in determining if an “aging signature” of skeletal muscle may exist and how this process may progress. Several projects will be undertaken in the lab, including: 1) identifying and analyzing genes that are differentially expressed in young and old muscle, 2) determining how these differently expressed genes may be regulated and if cellular stresses play a role in these changes, and 3) studying the epigenetic events (such as chromatin remodeling and DNA methylation) that may result from cellular stresses and ultimately contribute to long-term and irreversible changes in the heritable material. My lab will be using the mouse as a model organism, as well as cell culture and an array of molecular biological techniques to address the topics mentioned above and outlined below.