|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.
Fahrbach, S.E., Nambu, J.R. and Schwartz, L.M. 2012. Programmed cell death in insect neuromuscular systems during metamorphosis. In: Insect Molecular Biology and Biochemistry, L.I. Gilbert editor, pp 419-449.
Parelkar S.S., Cadena, J.G., Kim, C., Wang, Z., Sugal, R., Bentley, B., Moral, L., Ardley, H.C., and Schwartz, L.M. 201x. The Parkin-Like Human Homolog Of Drosophila Ariadne-1 (Hhari) Can Induce Aggresome Formation In Mammalian Cells And Is Immunologically Detectable In Lewy Bodies. Journal of Molecular Neuroscience, [Epub ahead of print] .
Chul, K., Srivastava, S. Rice, M., Godenschwege, T.A., Bentley, B., Ravi, S., Shao, S., Woodard, C.T., and Schwartz, L.M. 2011. Expression Of Human Amyloid Precursor Protein In The Skeletal Muscles Of Drosophila Results In Age- And Activity-Dependent Muscle Weakness. BMC Physiology, April 25. doi: 10.1186/1472-6793-11-7.
Shao, R., Scully, Jr., S.J., Yan, W., Bentley, B., Mueller, J., Brown, C., Bigelow, C., and Schwartz, L.M. 2011. The Novel Lupus Antigen Protein Acheron Enhances The Development Growth Of Human Breast Cancer. International Journal of Cancer, oi: 10.1002/ijc.26015. [Epub ahead of print] .
Glenn, H., Wang, Z., and Schwartz, L.M. 2010. Acheron, A Lupus Antigen Family Member, Regulates Integrin Expression, Adhesion, And Motility In Differentiating Myoblasts. American Journal of Physiology - Cell Physiology, 298: C46-55.
Hyldahl, R.D., O’Fallon, K.S., Schwartz, L.M., and Clarkson, P.M. 2010. Knockdown of metallothionein 1 and 2 does not affect atrophy or oxidant activity in cultured myotubes. Journal of Applied Physiology, 109: 1515-23.
Wang. Z., Valavanis, C., Glenn, H., Sun, D., Seth, A., Karlstrom, K., Schwartz, L.M. 2009. Acheron Is A Phylogenetically-Conserved Regulation. Mechanisms of Development, 126: 700-709.
Schwartz, L.M., Gao, Z., Brown, C., Parelkar S.S. and Glenn, H. 2009. Cell death in myoblasts and muscles. Methods Mol. Biol., 559: 313-332.
Yu, J-G., Sewright, K., Hubal, M.J., Liu, J-X., Schwartz, L.M., Hoffman, E.P., and Clarkson, P.M. 2009. An Investigation Of Gene Expression In C2C12 Myotubes Following Simvastatin Application And Mechanical Strain. Journal of Atherosclerosis and Thrombosis, 16: 21-29.
Myer, A., Mason, H.A., Smith, W., Brown, C. and Schwartz, L.M. 2009. Differential Control Of Cell Death And Gene Expression During Two Distinct Phases Of Hormonally-Regulated Muscle Death In The Tobacco Hawkmoth Manduca Sexta. Journal of Insect Physiology, 55: 314-320.
Weng, H., Kim, C., Valavanis, C., Wang, Z., and Schwartz, L.M. 2009. Acheron, a Novel La Antigen Family Member, Binds To CASK And Forms A Complex With Id Transcription Factors. Cellular and Molecular Biology Letters, 14:273-287.
Schwartz, L.M. 2008. Atrophy and programmed cell death of skeletal muscle. Cell Death and Differentiation. 15:1163-9.
Gao, Z., Deblis, R., Glenn, H., and Schwartz, L.M. 2007. Differential Role Of Hic-5 Isoforms On The Regulation Of Cell Death And Myotube Formation During Myogenesis. Experimental Cell Research, 313: 4000-14.
Bouchentouf, M., Benabdallah, B.F., Rousseau, J., Schwartz, L.M. and Tremblay, J.P. 2007. Induction of Anoikis following myoblast transplantation into SCID mouse muscles requires the Bit1 and FADD pathways. American Journal of Transplantation, 7: 1491–1505.
Valavanis, C., Wang, Z., Sun, D. Vaine, M., and Schwartz, L.M. 2007. Acheron, a novel member of the Lupus Antigen family, is induced during the programmed cell death of skeletal muscles in the moth Manduca Sexta. Gene, 393: 101–109.