Professor at University of Massachusetts-Amherst
schwartz@bio.umass.edu
Education
A.B., Northwestern University, 1976
Ph.D., U. Washington, Seattle, 1982
Postdoctoral
1982-1984 University of Washington, Seattle
1984-1987 University of North Carolina, Chapel Hill
1995-1996 Whitehead Institute for Biomedical Sciences
Research Interests
Programmed cell death is a fundamental component of development and homeostasis in virtually all organisms. Defects in the regulation of cell death serves as the basis of many human diseases, including auto-immunity, neurodegeneration and most cancers.
To define the molecular mechanisms that mediate this process, we have exploited the intersegmental muscles (ISM) of moth as a model system. These giant cells are used to propel the moth out of the pupal cuticle at the end of metamorphosis, and then they die during a 36 hour period in response to a specific hormonal trigger. The ability of the ISMs to commit suicide requires de novo gene expression and we have use a variety of molecular techniques to clone death-associated transcripts from these cells. As part of our on-going analysis of these novel genes, we have also cloned their mammalian homologs to determine their roles in myogenesis and disease.
Following declines in available trophic support, myoblasts make one of several key decisions. Some cells activate both survival and differentiation programs and fuse to form multinucleated myotubes. Others activate survival programs and arrest as mitotically-competent mononucleated satellite cells. The remainder die by apoptosis. The genes we initially isolated from the ISMs appear to play key roles in this decision making process. Not only does this work enhance our understanding of myogenesis as a developmental problem, but it may also provide powerful tools for regulating the survival of myoblasts that are used for transplantation for gene therapy.
A second line of investigation in our laboratory focuses on the regulation of skeletal muscle atrophy. Age- and disease-induced atrophy represents a major clinical problem, yet little is know about the molecular mechanisms that underlie this is regulated. We have found that some of the genes that we initially isolated from moth skeletal muscle play key regulatory roles in vertebrate atrophy, and we are pursuing this line of investigation with the hope of identifying potential therapeutic targets.
Lastly, we have begun to examine the role of the ubiquitin/proteasome system in the regulation of neuron survival in both insects and mammals. Deregulation of this pathway is responsible for several forms of familial Parkinsonism. Working with mouse and human material, we are trying to understand not only why dopaminergic neurons are endangered in these diseases, but also why other cells appear to be spared.