The question of fundamental interest in my laboratory is how cells maintain their differentiated state, and how they can change in response to injury. Using muscle as a model system, we first demonstrated in tissue culture that a range of highly specialized human adult cells could be induced to express previously silent muscle genes. Recently, we have found that such changes in cell fate also occur in vivo in mouse and man. Stem cells within adult bone marrow are capable of becoming muscle stem cells and muscle fibers in response to injury. These cells also can contribute to highly specialized neurons in the brain, such as Purkinje cells that are critical to movement and balance. Our current focus is to understand the regulatory mechanisms that govern these changes and potentially harness them therapeutically. We are seeking to identify and purify the cells that constitute this "repair squad" in bone marrow. In addition, we are characterizing the signals that recruit the stem cells within adult bone marrow and the route they take to get to tissues (blood vessels). Angiogenesis, the process by which blood vessels can be generated to rescue ischemic tissues, which also can be blocked to inhibit tumor progression, is another major focus of the lab's research. The Holy Grail of our research is to be able to administer drugs to help enlist the body to treat its own disease.

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