Research Interests: Molecular Mechanisms Controlling Apoptosis
One of the counter-intuitive aspects of biology is that all of our cells carry genetic programs that allow them to commit suicide. This process, known as apoptosis or programmed cell death (PCD), removes surplus or deleterious cells from our bodies. For example, the formation of fingers during embryogenesis requires the death of parallel rows of cells in the differentiating hand. Unfortunately, defects in the regulation of cell death serve as the basis for most human diseases, most notably neurodegeneration, auto-immunity, and most cancers.
We use the death of giant muscles during insect metamorphosis as a model system to define the molecular mechanisms that mediate PCD. Using a variety of molecular techniques, we demonstrated that PCD requires new gene expression and then cloned a number of these death-associated genes. Several of them encode previously characterized proteins involved in protein degradation, such as ubiquitin and proteasome subunits. Others encode novel proteins of previously unknown function.
One of the genes isolated in this screen encodes a new member of the lupus Antigen family of RNA proteins, which we have named Acheron. In addition to its role in the control of PCD in insects, Acheron is required for the normal development of muscles and neurons in vertebrates. Recently, we have found that Acheron is differentially expressed in some basal-like breast cancers in women and that Acheron may be driving angiogenesis and metastatic properties.
Center of Excellence in Apoptosis Research
Parelkar SS, Cadena JG, Kim C, Wang Z, Sugal R, Bentley B, Moral L, Ardley HC, Schwartz LM. Parkin-like human homolog of Drosophila ariadne-1 (Hhari-1) is present in lewy bodies and can induce aggresome formation in mammalian cells. J Mol Neurosci. In press (2011).
Chul K, Srivastava S, Rice M, Godenschwege TA, Bentley B, Ravi S, Shao S, Woodard CT, Schwartz LM. Expression of human amyloid precursor protein in the skeletal muscles of Drosophila results in age- and activity-dependent muscle weakness. BMC Physiol. In press (2011).
Shao R, Scully SJ Jr, Yan W, Bentley B, Mueller J, Brown C, Bigelow C, Schwartz LM. The novel lupus antigen protein acheron enhances the development growth of human breast cancer. Int J Cancer. In press (2011).
Glenn H, Wang Z, Schwartz LM. Acheron, a lupus antigen family member, regulates integrin expression, adhesion, and motility in differentiating myoblasts. Am J Physiol Cell Physiol. 2010;298(1):C46-C55.
Wang Z, Valavanis C, Glenn H, Sun D, Seth A, Karlstrom K, Schwartz LM. Regulation of muscle differentiation and survival by Acheron. Mech Dev. 2009;126(8-9):700-709.
Schwartz LM. Atrophy and programmed cell death of skeletal muscle. Cell Death Differ. 2008;15(7):1163-1169.
Fahrbach SE, Nambu JR, Schwartz LM. Programmed cell death in insect neuromuscular systems during metamorphosis. In: Gilbert LI, Latrou K, Gill SS, eds. Comprehensive Molecular Insect Science. Vol 2. Oxford, UK: Elsevier Pergamon; 2005:165-198.
Schwartz LM, Ashwell J, eds. Apoptosis. San Diego, CA: Academic Press; 2001:533. Methods in Cell Biology: vol 66.
Schwartz LM, McClesky EW, Almers W. Dihydropyridine receptors in muscle are voltage-dependent, but most are not functional calcium channels. Nature. 1985;314(6013):747-751.
Schwartz LM, Stühmer W. Voltage-dependent sodium channels in an invertebrate striated muscle. Science. 1984;225(4661):523-525.
Schwartz LM, Truman JW. Peptide and steroid regulations of muscle degeneration in an insect. Science. 1982;215:1420-1421.