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Joseph W. Sanger
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Emeritus Professor of Cell and Developmental Biology
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Department: Cell and Developmental Biology
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Contact information
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Laboratory for Cell Motility Studies
1d Room1014 BRB II/III.
34 Department of Cell and Developmental Biology
22 University of Pennsylvania
1a School of Medicine
3b 421 Curie Boulevard
Philadelphia, PA 19104-6058
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1d Room1014 BRB II/III.
34 Department of Cell and Developmental Biology
22 University of Pennsylvania
1a School of Medicine
3b 421 Curie Boulevard
Philadelphia, PA 19104-6058
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Office: 215 898-6919
32 Fax: 215 898-9871
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32 Fax: 215 898-9871
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Email:
SANGERJ@MAIL.MED.UPENN.EDU
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SANGERJ@MAIL.MED.UPENN.EDU
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Publications
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Education:
21 9 B.S. 3c (Major: Biology, Minor: Chemistry; with honors) c
38 Manhattan College, New York, NY, 1962.
21 a Ph.D. c
2d Dartmouth University, 1968.
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Permanent link21 9 B.S. 3c (Major: Biology, Minor: Chemistry; with honors) c
38 Manhattan College, New York, NY, 1962.
21 a Ph.D. c
2d Dartmouth University, 1968.
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bd Cellular analysis of the formation of myofibrils, stress fibers, and cleavage furrows in living cells, and mechanisms of movement of the infectious bacterium listeria monocytogenes.
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1f DESCRIPTION OF RESEARCH
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28d The heart is the first organ to differentiate and function in the embryo. Cardiac muscle cells synthesize sarcomeric proteins, which assemble into myofibrils. These early myofibrils are responsible for the first contractions and, later, for the continuous contractions of the growing heart with full capability of undergoing mitosis and cytokinesis. Upon cell division, myofibrils can disassemble into their component filaments and molecules, some of which are used to form the contractile cleavage furrow used in cytokinesis. The precise developmental cascade of myfibrillogenesis in both cardiac and skeletal muscle cells is poorly understood.
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2a3 As the spreading edges of the cell surface advance, the previously formed premyofibrils are left in place, which would permit other large proteins (e.g., muscle myosin II and titin) to gain access to the minisarcomeres. Premyofibrils are not, as some have suggested, breakdown products of mature myofibrils. The Z-bodies of the premyofibrils appear to fuse laterally with one another to form the Z-bands of mature myofibrils, and with increasing time, mature myofibrils and Z-bands emerge in regions where linear arrays of Z-bodies had been. A proposed three stage model of myofibril formation progresses with premyofibrils to nascent myofibrils to mature myofibrils.
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33d Premyofibrils, found at the spreading edges of the cardiomyocytes, are composed of minisarcomeres. The sarcomeric equivalent of the Z-band in the premyofibril is a Z-body; both contain the cytoskeletal protein alpha actinin. This protein is found concentrated in stress fibers, Z-bodies and Z-bands of muscles marking the boundaries of the sarcomeric units in nonmuscle stress fibers and in muscle myofibrils. Our results have demonstrated premyofibrils precede in space and time to mature myofibrils. These beaded Z-bodies are attached to the cell surface and are responsible for the attachment of the short actin filaments to the cell surfaces. Most importantly, premyofibrils contain nonmuscle myosin IIB, which is believed to be responsible for the antipolar arrangement of the actin filaments in these minisarcomeres.
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Description of Research Expertise
24 RESEARCH INTERESTS8
bd Cellular analysis of the formation of myofibrils, stress fibers, and cleavage furrows in living cells, and mechanisms of movement of the infectious bacterium listeria monocytogenes.
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1f DESCRIPTION OF RESEARCH
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28d The heart is the first organ to differentiate and function in the embryo. Cardiac muscle cells synthesize sarcomeric proteins, which assemble into myofibrils. These early myofibrils are responsible for the first contractions and, later, for the continuous contractions of the growing heart with full capability of undergoing mitosis and cytokinesis. Upon cell division, myofibrils can disassemble into their component filaments and molecules, some of which are used to form the contractile cleavage furrow used in cytokinesis. The precise developmental cascade of myfibrillogenesis in both cardiac and skeletal muscle cells is poorly understood.
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2a3 As the spreading edges of the cell surface advance, the previously formed premyofibrils are left in place, which would permit other large proteins (e.g., muscle myosin II and titin) to gain access to the minisarcomeres. Premyofibrils are not, as some have suggested, breakdown products of mature myofibrils. The Z-bodies of the premyofibrils appear to fuse laterally with one another to form the Z-bands of mature myofibrils, and with increasing time, mature myofibrils and Z-bands emerge in regions where linear arrays of Z-bodies had been. A proposed three stage model of myofibril formation progresses with premyofibrils to nascent myofibrils to mature myofibrils.
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33d Premyofibrils, found at the spreading edges of the cardiomyocytes, are composed of minisarcomeres. The sarcomeric equivalent of the Z-band in the premyofibril is a Z-body; both contain the cytoskeletal protein alpha actinin. This protein is found concentrated in stress fibers, Z-bodies and Z-bands of muscles marking the boundaries of the sarcomeric units in nonmuscle stress fibers and in muscle myofibrils. Our results have demonstrated premyofibrils precede in space and time to mature myofibrils. These beaded Z-bodies are attached to the cell surface and are responsible for the attachment of the short actin filaments to the cell surfaces. Most importantly, premyofibrils contain nonmuscle myosin IIB, which is believed to be responsible for the antipolar arrangement of the actin filaments in these minisarcomeres.
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12e Malish, H. R. N. L. Freeman, D. V. Zurawski, P. Chowrashi, J. C. Ayoob, , J. W. Sanger, and J. M. Sanger: Potential Role of the EPEC Translocated Intimin Receptor (Tir) in Host Apoptotic Events. Apoptosis 8: 179-90, Mar 2003.
f9 Du A, Sanger JM, Linask KK, Sanger JW. : Myofibrillogenesis in the first cardiomyocytes formed from isolated quail precardiac mesoderm. Dev Biol. 257(2): 382-94, May 15 2003.
132 Huang, L., Mittal, B., Sanger, J. W. and Sanger, J. M.: Host focal adhesion protein domains that bind to the translocated intimin receptor (Tir) of Enteropathogenic Escherichia coli (EPEC). Cell Motil. Cytoskeleton 52: 255-265, 2002.
12e Zajdel, R. W., J. M. Sanger, C. R. Denz, S. Lee, S. Dube, J. W. Sanger and D. K. Dube: A novel striated tropomyosin incorporated into organized myofibrils of cardiomyocytes in cell and organ cultures. FEBS Lett. 520: 35-39, 2002.
ff Chowrashi, P., B. Mittal, J. M. Sanger and Joseph W. Sanger: Amorphin is phosphorylase; phosphorylase is an alpha-actinin-binding protein. Cell Motil. Cytoskeleton 53: 125-135, 2002.
106 Sanger, J. W., P. Chowrashi, N. C.Shaner , S. Spalthoff , J. Wang , N. Freeman , and J. M. Sanger: Myofibrillogenesis in skeletal muscle cells. Clin Ortho Related Res 403S: S153-S162, 2002.
101 Shaner, N. C., J. W. Sanger and J. M. Sanger: Lowering of cellular ATP levels inhibits actin depolymerization in EPEC/EHEC pedestals and Listeria tails. Mol. Biol. Cell 13: 177a, 2002.
f3 Wang, J., B. Mittal, M. Lee, J. M. Sanger and J. W. Sanger: Spatial, temporal and dynamic studies of Z-band proteins in live muscle cells. Mol. Biol. Cell 13: 459a, 2002.
ee Du, A., J. M. Sanger and J. W. Sanger: Myofibrillogenesis in the first cardiomyocytes formed from isolated quail precardiac mesoderm. Mol. Biol. Cell 13: 459a, 2002.
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Selected Publications
10a Sanger, J. W., J. M. Sanger and C. Franzini-Armstrong: Assembly of the skeletal muscle cell. Myology, 3rd Edition. A. G. Engel and C. Franzini-Armstrong (eds.). McGraw-Hill, New York, In Press.12e Malish, H. R. N. L. Freeman, D. V. Zurawski, P. Chowrashi, J. C. Ayoob, , J. W. Sanger, and J. M. Sanger: Potential Role of the EPEC Translocated Intimin Receptor (Tir) in Host Apoptotic Events. Apoptosis 8: 179-90, Mar 2003.
f9 Du A, Sanger JM, Linask KK, Sanger JW. : Myofibrillogenesis in the first cardiomyocytes formed from isolated quail precardiac mesoderm. Dev Biol. 257(2): 382-94, May 15 2003.
132 Huang, L., Mittal, B., Sanger, J. W. and Sanger, J. M.: Host focal adhesion protein domains that bind to the translocated intimin receptor (Tir) of Enteropathogenic Escherichia coli (EPEC). Cell Motil. Cytoskeleton 52: 255-265, 2002.
12e Zajdel, R. W., J. M. Sanger, C. R. Denz, S. Lee, S. Dube, J. W. Sanger and D. K. Dube: A novel striated tropomyosin incorporated into organized myofibrils of cardiomyocytes in cell and organ cultures. FEBS Lett. 520: 35-39, 2002.
ff Chowrashi, P., B. Mittal, J. M. Sanger and Joseph W. Sanger: Amorphin is phosphorylase; phosphorylase is an alpha-actinin-binding protein. Cell Motil. Cytoskeleton 53: 125-135, 2002.
106 Sanger, J. W., P. Chowrashi, N. C.Shaner , S. Spalthoff , J. Wang , N. Freeman , and J. M. Sanger: Myofibrillogenesis in skeletal muscle cells. Clin Ortho Related Res 403S: S153-S162, 2002.
101 Shaner, N. C., J. W. Sanger and J. M. Sanger: Lowering of cellular ATP levels inhibits actin depolymerization in EPEC/EHEC pedestals and Listeria tails. Mol. Biol. Cell 13: 177a, 2002.
f3 Wang, J., B. Mittal, M. Lee, J. M. Sanger and J. W. Sanger: Spatial, temporal and dynamic studies of Z-band proteins in live muscle cells. Mol. Biol. Cell 13: 459a, 2002.
ee Du, A., J. M. Sanger and J. W. Sanger: Myofibrillogenesis in the first cardiomyocytes formed from isolated quail precardiac mesoderm. Mol. Biol. Cell 13: 459a, 2002.
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