Welcome to the Medical and MolecularW Physiology Graduate ProgramW
at the

Institute for Biogenesis Research
Research Description


W. Steven Ward, Ph.D.

Phone:  (808) 956-5189
Fax:  (808) 956-7316 
Email: wward@hawaii.edu

Biomedical Tower, IBR Building
Manoa Campus

Ph.D. Biochemistry, Vanderbilt University 1985

Reproductive Biology

The Structure and Function of Sperm DNA

Our laboratory has focused on the three dimensional structure of DNA in the cell, using sperm as a model system.  Sperm chromatin is packaged in a unique way to protect the DNA from damage during fertilization.  We have shown that some aspects of sperm DNA packaging are surprisingly similar to that of all other cell types, revealing some of the foundation principles for DNA packaging.  We have also shown that some aspects are very different, in which parts of the sperm DNA is packaged like a crystal.  Recently, we have also made the surprising discovery that even though sperm DNA is very highly packaged, it has a self-destruct mechanism that enables it to chew up all its DNA before fertilization.  We believe this is an evolutionary mechanism to prevent the passage of damaged DNA to the new embryo.  Our current work is focused on identifying this activity and how it relates to the packaging principles we previously discovered.  Finally, we have recently become interested in SINE repeats in the human and mouse genomes.  We have demonstrated that virtually every Alu and B1 repeat is a single copy sequence.  We are currently testing whether SINES are expressed in cell-specific manners.

1. Comparison of somatic and sperm Chormatin packaging

2. Visualization of DNA loop domains shown in Figure 1E and J

3. Model for the interaction of sperm Topoismerase II and a nuclease to degrade sperm DNA


Selected Publications

  1. Ward, W.S., Schmidt, W.N., Schmidt, C.A. and Hnilica, L.S.:  Association of cytokeratin p39 with DNA in intact Novikoff hepatoma cells.  Proc. Natl. Acad. Sci. USA  81:419-423, 1984. .pdf
  2. Wedrychowski, A., Ward, W.S., Schmidt, W.N. and Hnilica, L.S.  Chromium induced crosslinking of nuclear proteins and DNA.  J. Biol. Chem.  260: 7150-7155, 1985. .pdf
  3. Ward, W.S., Schmidt, W.N., Schmidt, C.A. and Hnilica, L.S.:  Crosslinking of the Novikoff ascites hepatoma cytokeratin Filaments.  Biochem.  24:4429-4434, 1985.
  4. Ward, W.S., Partin, A.W., and Coffey, D.S.:  DNA loop domains in mammalian spermatozoa.  Chromos.  98:153-159, 1989.
  5. Ward, W.S. and Coffey, D.S.:  Identification of a sperm nuclear annulus:  a sperm DNA anchor.  Biol. Reprod.  41:361-370, 1989. .pdf
  6. Ward, W.S., and Coffey, D.S.:  Specific organization of genes in relation to the sperm nuclear matrix.  Biochem. Biophys. Res. Comm.  173:20-25, 1990.
  7. Ward, W.S., and Coffey. D.S.:  DNA packaging and organization in mammalian spermatozoa: comparison with somatic cells.  Biol. Reprod.  44:569-574, 1991. .pdf
  8. Ward, W. S.:  DNA loop domain tertiary structure in mammalian spermatozoa.  Biol. Reprod.  48:1193-1201, 1993. .pdf
  9. Ward, W. S.:  The structure of the sleeping genome:  implications of sperm DNA organization for somatic cells.  J. Cell. Biochem.  55:77-82 1994. .pdf
  10. Nadel, B., de Lara, J., Finkernagel, S. W., and Ward, W. S.:  Cell specific organization of the 5S rRNA gene cluster DNA loop domains in spermatozoa and somatic cells.  Biol. Reprod. 53;1222-1228, 1995. .pdf
  11. Ward, W. S., McNeil, J., de Lara, J,, Lawrence, J. “Localization of three genes in the hook-shaped hamster sperm nucleus by fluorescent in situ hybridization.”  Biol. Reprod. 54(6):1271-1278, 1996. .pdf
  12. Ward, W. S., and Zalensky, A.  "The Unique, Complex Organization of the Transcriptionally Silent Sperm Chromatin".  Critical Reviews in Eukaryotic Gene Expression, 6:139-148, 1996.
  13. W. Steven Ward,  “Chromosome Organization in Mammalian Sperm Nuclei”.  In: Genetics of Human Male Fertility. Eds: Barratt, C., De Jonge, C., Mortimer, D., and Parinaud, J., Editions E.D.K., Paris.  pp. 147-163, 1997.
  14. Ward, W. S., Kimura, Y., Yanagimachi, R., “An Intact Sperm Nuclear Matrix May be Necessary for the Paternal Genome to Participate in Embryonic Development”. Biology of Reproduction, 60:702-706, 1999. .pdf
  15. Ward, W. S., Kishikawa, H., Akutsu, H., Yanagimach, H., and Yanagimach, R.  “Further Evidence that Sperm Nuclear Proteins are Necessary for Embryogenesis”.   Zygote, 8:51-56, 2000. .pdf
  16. McCarthy, S., and Ward, W. S.  “Interaction of Exogenous DNA with the Nuclear Matrix of Live Spermatozoa”.  Molecular Reproduction and Development, 56:235-7, 2000. .pdf
  17. Barone, J.G., Christiano, A. P., and Ward, W. S.  “DNA Organization in Patients with a History of Cryptorchidism”. Urology 56(6):1-3, 2000. .pdf
  18. Barbara Sotolongo and W. Steven Ward. “DNA Loop Domain Organization: The Three Dimensional Genomic Code” Journal of Cellular Biochemistry, 35:23-26, 2001. .pdf
  19. Angela V. Klaus, John R. McCarrey, Andrew Farkas, and W. Steven Ward.  “Changes in DNA Loop Domain Structure During Spermatogenesis and Embryogenesis in the Syrian Golden Hamster”.  Biology of Reproduction, 64:1297-1306,  2001. .pdf
  20. W. Steven Ward. “Building a Road to Defeat Prostate Cance

    r:  A Dedication to Donald S. Coffey”, in:  Prostate Cancer, eds. Leland W. K. Chung, William B. Isaacs, and Jonathan W. Simons, Human Press, Totowa, N.J.  2001. .pdf
  21. Isaac Mohar, Monika A. Szczygiel, Ryuzo Yanagimachi, and W. Steven Ward.  “Sperm Nuclear Halos Can Transform into Normal Chromosomes after Injection into Oocytes”, Molecular Reproduction and Development, 63:416-420, 2002. .pdf
  22. Ankem MK, Mayer E, Ward WS, Cummings KB, Barone JG.  “Novel assay for determining DNA organization in human spermatozoa: implications for male factor infertility.   Urology 59:575-8, 2002 .pdf
  23. Monika A. Szczygiel and W. Steven Ward.  “Combination of DTT and detergent treatment of spermatozoa causes paternal chromosomal damage”,  Biology of Reproduction, 67, 1532–1537, 2002. .pdf
  24. Monika A. Szczygiel, Stefan Moisyadi, W. Steven Ward.  “Expression of foreign DNA is associated with paternal chromosome degradation in ICSI-mediated transgenesis in the mouse.”  Biology of Reproduction, 68:1903-1910, 2003. .pdf
  25. Barbara Sotolongo, Elisabete Lino, and W. Steven Ward.  “Hamster Spermatozoa have the Ability to Digest Their Own DNA”, Biology of Reproduction, 69, 2029–2035, 2003. .pdf
  26. Monika A. Ward and W. Steven Ward.  “Functional Aspects of Mammalian Sperm Chromatin Structure”, Fertility, Reproduction and Development, Vol. 16 (5): 547-554, 2004. .pdf
  27. Barbara Sotolongo, Thomas T. F. Huang, Elisabete Isenberger, and W. Steven Ward. “An Endogenous Nuclease in Hamster, Mouse and Human Spermatozoa Cleaves DNA into Loop-Sized Fragments”.   Journal of Andrology 26:272-280, 2005. .pdf
  28. Jeffrey A. Shaman, and W. Steven Ward. “Sperm DNA Stability”, in, The Sperm Cell: Production, Maturation, Fertilization, Regeneration Editors: Christopher De Jonge & Christopher L.R. Barratt.  Cambridge University Press, 2006. .pdf
  29. Jeffery A. Shaman, Renata Prisztoka, and W. Steven Ward.  Topoisomerase IIB and an Extracellular Nuclease Interact to Digest Sperm DNA in an Apoptotic-Like Manner.  Biology of Reproduction, 75:741-748, 2006. .pdf 
  30. Boris Umylny, Gernot Presting, Jimmy T. Efird, Boris I. Klimovitsky, and W. Steven Ward.  “Most human Alu and murine B1 repeats are unique.”  Journal of Cellular Biochemistry, 102:110-121, 2007. .pdf
  31. Jeffrey A. Shaman, Yasuhiro Yamauchi, and W. Steven Ward. “Sperm DNA Fragmentation: Awakening the Sleeping Genome.”  Biochemical Society Transactions, 35:626-628, 2007. .pdf
  32. Yasuhiro Yamauchi, Jeffrey A. Shaman, and W. Steven Ward.  “Topoisomerase II Mediated Breaks in Spermatozoa Cause the Specific Degradation of Paternal DNA in Fertilized Oocytes”.  Biology of Reproduction, 76:666-672, 2007. .pdf
  33. Jeffrey A. Shaman, Yasuhiro Yamauchi, and W. Steven Ward.  “The Sperm Nuclear Matrix is Required for Paternal DNA Replication”.  Journal of Cellular Biochemistry, 102:680-688, 2007. .pdf
  34. Jeffrey A. Shaman, Yasuhiro Yamauchi, and W. Steven Ward. ”Function of the Sperm Nuclear Matrix”.  Archives of Andrology, 53:135-140, 2007. .pdf
  35. Boris Umylny, Gernot Presting, and W. Steven Ward.  “Evidence of Alu and B1 expression in dbEST”  Archives of Andrology, 53:207-218, 2007. .pdf
  36. Yasuhiro Yamauchi, Jeffrey A. Shaman, Segal M. Boaz, and W. Steven Ward.  “Paternal Pronuclear DNA Degradation is Functionally Linked to DNA Replication in Mouse Oocytes”.  Biology of Reproduction, 77:407-415, 2007. .pdf
  37. Segal M. Boaz, Kenneth Dominguez, Jeffrey A. Shaman, and W. Steven Ward.  “Mouse Spermatozoa Contain a Nuclease that Is Activated by Pretreatment with EGTA and Subsequent Calcium Incubation.”  Journal of Cellular Biochemistry, 103:1636-1645, 2008. .pdf
  38. Yasuhiro Yamauchi, Monika A. Ward, and W. Steven Ward. “Asynchronous DNA Replication and Origin Licensing in the Mouse One Cell Embryo Journal of Cellular Biochemistry, in press, 2009. .pdf