|Lawrence M. Schwartz
Professor of Biology, University of Massachusetts
Director, Pioneer Valley Life Sciences Institute(PVLSI)
Ph.D.: University of Washington
M olecular Mechanisms Controlling Programmed Cell Death
Programmed cell death is a fundamental component of development in virtually all organisms. For example, the formation of fingers during embryogenesis requires the death of parallel rows of cells in the differentiating hand. By exploiting rapid death of the intersegmental muscles of moth at the end of metamorphosis as a model system, we have cloned a number of death-associate genes. We have taken advantage of the powerful genetic tools that exist in the fruit fly Drosophila to study the function of these genes during insect development. We have also cloned the mouse and human homologs of these genes and demonstrated that they serve comparable roles in regulating cell survival and differentiation in mammals.
While we have worked on a variety of different taxa and tissues, current experiments in the laboratory predominantly focus on the differentiation of mammalian myoblasts. Following declines in available trophic support, these cells make one of several choices: 1) die; 2) activate survival programs and arrest as mitotically-competent myoblasts; or 3) activate both survival and differentiation programs and form multinucleated myotubes. Working with cell in vitro, we have found that the genes we initially identified from moth play key roles in regulating these decisions. Parallel experiments have been initiated to study the mechanisms by which these genes regulate development in vivo. In separate studies, we are examining human pathological materials to determine if the mis-regulation of these genes contribute to disease.
Schwartz, L. M., J. R. Nambu and Z. Wang (2002). "Parkinsonism proteolysis and proteasomes." Cell Death Differ 9(5): 479-82.
Schwartz, L. M. and R. L. Ruff (2002). "Changes in contractile properties of skeletal muscle during developmentally programmed atrophy and death." Am J Physiol Cell Physiol 282(6): C1270-7.
Wing, J. P., J. S. Karres, J. L. Ogdahl, L. Zhou, L. M. Schwartz and J. R. Nambu (2002). "Drosophila sickle is a novel grim-reaper cell death activator." Curr Biol 12(2): 131-5.
Wing, J. P., B. A. Schreader, T. Yokokura, Y. Wang, P. S. Andrews, N. Huseinovic, C.
K. Dong, J. L. Ogdahl, L. M. Schwartz, K. White and J. R. Nambu (2002). "Drosophila Morgue is an F box/ubiquitin conjugase domain protein important for grim-reaper mediated apoptosis." Nat Cell Biol 4(6): 451-6.
Valavanis, C., Y. Hu, Y. Yang, B. A. Osborne, S. Chouaib, L. Greene, J. D. Ashwell and L. M. Schwartz (2001). "Model cell lines for the study of apoptosis in vitro." Methods Cell Biol 66: 417-36.
Valavanis, C., S. Naber and L. M. Schwartz (2001). "In situ detection of dying cells in normal and pathological tissues." Methods Cell Biol 66: 393-415.
Shumway, L. and L. M. Schwartz (2001). "Generalized 96-well format for quantitative and qualitative monitoring of altered protein expression and posttranslational modification in cells." Biotechniques 31(5): 996, 998, 1000.
Cascone, P. J. and L. M. Schwartz (2001). "Post-transcriptional regulation of gene expression during the programmed death of insect skeletal muscle." Dev Genes Evol 211(8-9): 397-405.
Schwartz, L. M., L. Sebbag, R. B. Jennings and K. A. Reimer (2001). "Duration and reinstatement of myocardial protection against infarction by ischemic preconditioning in open chest dogs." J Mol Cell Cardiol 33(9): 1561-70.
Kuelzer, F., P. Kuah, S. T. Bishoff, L. Cheng, J. R. Nambu and L. M. Schwartz (1999).