Lawrence M. Schwartz

Research Interests: 

Programmed Cell Death

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 remainders die by apoptosis. The genes we initially isolated from the ISMs appear to play key roles in this decision making process. For example, Acheron acts early in myogenesis to determine if myoblasts should remain as lineage-restricted stem cells or instead differentiate or die. Thus, not only does this work enhance our understanding of myogenesis as a developmental process, but it may also provide powerful tools for regulating the survival of myoblasts that are used for regenerative medicine and gene therapy.