Lawrence M. Schwartz, Ph.D.

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 30 hr 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. Recently, we performed a comprehensive RNA-seq transcriptomics analysis of both the mRNAs and small RNAs to identify all of the differentially expressed genes, as well as the microRNAs that regulate their stability and translatability.  We are currently expanding this analysis to examine skeletal muscle disorders in mammals.

Selected Papers:

Schwartz, L.M. (2019) Skeletal Muscles Do Not Undergo Apoptosis During Either Atrophy or Programmed Cell Death-Revisiting the Myonuclear Domain Hypothesis.  Frontiers in Physiology. 9:1887. doi: 10.3389/fphys.2018.01887

Sheel, A, Shao, R., Brown, C., Johnson, J., Hamilton, A., Oppenheimer, J., Smith, W., Visconti, P., Markstein, M., and Schwartz, L.M. (2020)Acheron/LARP6 is a Novel Survival Protein that Controls Programmed Cell Death During Development. Frontiers in Cell and Developmental Biology, 8:622   doiI=10.3389/fcell.2020.00622  

Tsuji J, Thomson T, Chan E, Brown CK, Oppenheimer J, Bigelow C, Dong X, Theurkauf WE, Weng Z, Schwartz LM. (2020) High Resolution Analysis of Differential Gene Expression During Skeletal Muscle Atrophy and Programmed Cell Death. Physiological Genomics. 52:492-511

Schwartz, L.M. (2019) Skeletal Muscles Do Not Undergo Apoptosis During Either Atrophy or Programmed Cell Death- Rejection of The Myonuclear Domain Hypothesis. Frontiers in Physiology, 9:1887. doi: 10.3389/fphys.2018.01887

Hayes, KL, Messina, L.M., Schwartz, L.M., Yan, J., and Witkowski, S (2018) Type 2 diabetes impairs the ability of skeletal muscle pericytes to augment postischemic neovascularization via impaired collateral artery enlargement and engraftment into collateral vessels in mice. American Journal of Physiology. 314:C534-C544

Ngernyuang, N., Yan, W., Schwartz, L.M., Chen, H., and and Shao, R. (2017) A Heparin Binding Motif Rich in Lysine and Arginine Is the Functional Domain of YKL-40. Neoplasia, 20:182–192. 

Kanost, MR, Arrese, EL, Cao, X. Chen Y-R., et al (2016) Multifaceted Biological Insights from a Draft Genome Sequence of the Tobacco Hornworm Moth, Manduca sexta. Insect Biochemistry and Molecular Biology, Insect Biochem Mol Biol. 76:118-47.

Schwartz, L.M., Brown, C., McLaughlin, K., Smith, W., and Bigelow, C. (2016) The Myonuclear Domain Is Not Maintained During Skeletal Muscle Atrophy or Programmed Cell Death. American Journal of Physiology- Cell Physiology, 311:C607-C615.

Shao, R., Taylor, S.L., Oh, D.S., and Schwartz, L.M. (2015) Vascular Heterogeneity: The Role of YKL-40 in Glioblastoma Vascularization. Oncotarget, 6:40507-18.

Cao, X., He, Y., Hu, Y., Wang, Y, Chen, Y-R., Bryant, B., Clem, R.J., Schwartz, L.M., Blissard, G., Jiang, H. (2015) The immune signaling pathways of Manduca sexta. Insect Biochemistry and Molecular Biology, 62:64-74.

Schwartz, LM (2013) Muscle Nuclei Remember To Cheat Death. Journal of Physiology. 6133–6134.

Hyldahl RD, Schwartz LM, Clarkson PM. (2013) NF-kB Functions in Primary Pericyte Cells in a Cell- and Non-Cell Autonomous Manner to Affect Myogenesis. Muscle and Nerve, 47:522-531.

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] .

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.

Schwartz, L.M. 2008. Atrophy and programmed cell death of skeletal muscle. Cell Death and Differentiation. 15:1163-9.

Wing J.P., Schreader, B.A., Wang, Y., Andrews, P.A., Husseinovic, N., Dong, C.K. Ogdahl, J., Schwartz, L.M., White, K., Nambu, J.R. 2002. Drosophila Morgue is a novel F box/ubiquitin conjugase domain protein important in grim-reaper mediated programmed cell death. Nature Cell Biology, 4: 451-456.

Wing, J.P., Karres, J., Ogdahl, J.A., Zhou, L., Schwartz, L.M. and Nambu, J.R. 2002. Drosophila sickle is a novel grim-reaper cell death activator. Current Biology, 12: 131–135.

Schwartz, L.M. and Ashwell, J. 2001. Editors Methods in Cell Biology Series, Apoptosis. Academic Press, volume 66, pp533.

Hu, Y., Cascone, P., Cheng, L., Sun, D., Nambu, J.R., and Schwartz, L.M. 1999. Lepidopteran DALP, And Its Mammalian Ortholog Hic-5, Function as Negative Regulators of Muscle Differentiation. Proc. Natl. Acad. Sci. USA, 96: 10218-10223.

Zhou, L., Schnitzler, A., Agapite, J., Schwartz, L.M., Steller, H., and Nambu, J.R. 1997. Cooperative functions of the reaper and head involution defective genes in the programmed cell death of Drosophila CNS midline cells. Proc. Natl. Acad. Sci. USA, 94: 5131-5136.

Schwartz, L.M. and Osborne, B.A. 1995. Editors Methods in Cell Biology Series, CELL DEATH. Academic Press, pp459.

Milligan, C.E., Prevette, D., Yaginuma, H., Homma, S., Cardwell, C., Fritz, L.C., Tomeselli, K.J., Oppenheim, R.W. and Schwartz, L.M. 1995. Peptide inhibitors of the ICE protease family arrest programmed cell death of motoneurons in vitro and in vivo. Neuron, 15: 385-393.

Liu, Z-G., Smith, S., McLaughlin, K.A., Schwartz, L.M. and Osborne B.A. 1994. Apoptotic Signals Delivered Through the T Cell Receptor Require the Immediate Early Gene Nur77. Nature, 367: 281-284.

Schwartz, L.M., Smith, S., Jones, M.E.E., and Osborne B.A. 1993. Do All Programmed Cell Deaths Occur Via Apoptosis? Proc. Natl. Acad. Sci. USA, 90: 980-984.

Schwartz, L.M., Myer, A., Kosz, L., Engelstein, M., and Maier, C. 1990. Activation of Polyubiquitin Gene Expression during Developmentally Programmed Cell Death. Neuron, 5: 411-419.

Schwartz, L.M., Kosz, L., and Kay, B.K. 1990. Gene Activation is Required for Developmentally Programmed Cell Death. Proc. Natl. Acad. Sci. USA, 87: 6594-6598.

Schwartz, L.M., McClesky, E.W. and Almers, W. 1985. Dihydropyridine Receptors in Muscle are Voltage-Dependent, But Most Are Not Functional Calcium Channels. Nature, 314: 747-751.

Schwartz, L.M. and Stühmer, W. 1984. Voltage-Dependent Sodium Channels in an Invertebrate Striated Muscle. Science, 225: 523-525.

Schwartz, L.M. and Truman, J.W. 1984. Cyclic GMP May Serve as a Second Messenger in Peptide-Induced Muscle Degeneration in an Insect. Proc. Natl. Acad. Sci. USA, 81: 6718-6722.

Schwartz, L.M. and Truman, J.W. 1982. Peptide and Steroid Regulation of Muscle degeneration in an Insect. Science, 215: 1420-1421.