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W. Steven Ward, PhD

W. Steven Ward, PhD

Professor and Director of the IBR

Steven Ward Profile Image



  • Affiliation:
    Anatomy, Biochemistry & Physiology
    Obstetrics, Gynecology & Women's Health

  • Email: wward@hawaii.edu

  • Phone: (808)956-5189

Short Bio

Dr. Ward attended Belmont Abbey College for three years in his native North Carolina before travelling abroad to complete his B.S. in chemistry and his M.S. in biochemistry at the American University of Beirut. He continued his graduate education at Vanderbilt University where he earned his PhD in biochemistry in 1985. His dissertation focused on chromatin structure in rat liver cancer cells, and he provided the first evidence that cytokeratins can be associated with DNA. He then spent five years as an oncology fellow under the mentorship of Donald S. Coffey at Johns Hopkins University Medical School. The labs were located in the Department of Urology and Dr. Ward worked closely with academic urologists, residents and medical students and developed a strong background in clinical research. During this time, he identified the major components of tertiary sperm chromatin structure, which remains the current focus of his research. From 1990 to 2000, Dr. Ward was the Director of Urologic Research, in the Division of Urology, Department of Surgery at the Robert Wood Johnson Medical School in New Brunswick, New Jersey. He continued to develop his own research in sperm chromatin structure, and became a recognized expert in the field internationally. He also oversaw resident research projects for 20 residents, participated in faculty development, and was an important part of the development of the New Jersey Cancer Institute. In 2000 he was recruited to the University of Hawaii to help develop the new Institute for Biogenesis Research (IBR). He continued to be productive in research in both sperm chromatin structure but expanded his focus to include oogenesis and follicuologenesi. In 2005 he was named the Interim director of the IBR, and in 2008 was appointed its permanent director. Dr. Ward has been continuously funded by the NIH since 1991. From 2009 through 2025, he was awarded a Center of Biomedical Research Excellence (COBRE) grant from the NIH to support the development of ten faculty in the IBR and the center, itself. Because of his experience in clinical research and leadership, in 2014 he was appointed the Chief of the Division of Research in the Department of Obstetrics and Gynecology at the John A. Burns School of Medicine.

Graduate Faculty

DRB, CMB

Research Interests

Our lab has been interested in chromatin structure during spermiogenesis and embryogenesis. We began with understanding how DNA in the sperm cell is packaged. Sperm DNA is the most compact DNA in any biological system, including viruses, and our work lead to a model for sperm chromatin structure that is widely accepted. It is based on the organization of sperm DNA into loop domains that are probably inherited by the embryo after fertilization. We are interested in how this organization in the sperm cell leads to proper DNA replication in the embryo of the paternal genome after fertilization, and have demonstrated that loop domain organization is a key feature of this. In the course of our paternal DNA replication work, we discovered that a key protein involved in DNA origin identification, ORC4, also plays a role in chromatin expulsion during female meiosis, and in erythrocyte chromatin expulsion. In the course of the ORC4 work, we discovered that EXOC5 is required for folliculogenesis. The first wave of folliculogenesis with Exoc5 deleted in oocytes develops to the antral follicle stage, but he oocytes are compromised and all subsequent waves arrest in the pre-antral stages. Thus, our laboratory now has three foci of interests: Sperm chromatin structure, early embryonic DNA replication, and the biology of early folliculogenesis.

Selected Publications

http://www.ncbi.nlm.nih.gov/myncbi/browse/collection/40514243/?sort=date&direction=ascending

1. Ward, W. S., and Coffey, D. S. “Specific organization of genes in relation to the sperm nuclear matrix.” Biochemical and Biophysical Research Communications 173:20-25, 1990. PMID: 2175176

2. Ward, W. S. “DNA loop domain tertiary structure in mammalian spermatozoa.” Biology of Reproduction 48:1193-1201, 1993. PMID: 8318576

3. 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.” Biology of Reproduction 53;1222-1228, 1995. PMID: 8527528

4. Klaus, A. V., McCarrey, J. R., Farkas, A., and Ward, W. S. “Changes in DNA Loop Domain Structure During Spermatogenesis and Embryogenesis in the Syrian Golden Hamster.” Biology of Reproduction, 64:1297-1306, 2001. PMID: 11319132

5. Mohar, I., Szczygiel, M. A., Yanagimachi, R., and Ward, W. S. “Sperm Nuclear Halos Can Transform into Normal Chromosomes after Injection into Oocytes”, Molecular Reproduction and Development 63:416-420, 2002. PMID: 12112607

6. Sotolongo, B., Lino, E., and Ward, W. S. “Hamster Spermatozoa have the Ability to Digest Their Own DNA”, Biology of Reproduction 69, 2029–2035, 2003. PMID: 12930713

7. Shaman, J. A., Yamauchi, Y., and Ward, W. S. “The Sperm Nuclear Matrix is Required for Paternal DNA Replication”. Journal of Cellular Biochemistry, 102:680-688, 2007. PMID: 17415751

8. Yamauchi, Y., Shaman, J. A., Boaz, S. M., and Ward, W. S. “Paternal Pronuclear DNA Degradation is Functionally Linked to DNA Replication in Mouse Oocytes”. Biology of Reproduction, 77:407-415, 2007. PMID: 17494913

9. Yamuchi, Y., Ward, M. A., and Ward, W. S. “Asynchronous DNA Replication and Origin Licensing in the Mouse One Cell Embryo” Journal of Cellular Biochemistry, 107:214-223, 2009. PMCID: PMC2758055. PMID: 19301258

10. Ward, W. S., “Function of Sperm Chromatin Structural Elements in Fertilization and Development”. Molecular Human Reproduction, 16:30-36, 2010. PMCID: PMC2790366. PMID: 19748904

11. Ortega, M. A., Marh, J., Alarcon, V., & Ward, W. S. “Unique Pattern of ORC2 and MCM7 Localization During DNA Replication Licensing in the Mouse Zygote”. Biology of Reproduction, 87:62, 2012. PMID: 22674395; PMCID:PMC3463414. PMID: 22674395

12. Nguyen, H., Ortega, M. A., Ko, M., Marh, J., Ward, W. S. “ORC4 Surrounds Extruded Chromatin in Female Meiosis”. Journal of Cellular Biochemistry, 116:778-786, 2015. PMID: 25502171; PMCID: PMC4355034

13. Gawecka, J. E., Boaz, S., Kasperson, K., Nguyen, H., Evenson, D. P., Ward, W. S. “Luminal Fluid of Epididymis and Vas Deferens Contributes to Sperm Chromatin Fragmentation.” Human Reproduction, 30:2725-36, 2015. PMID: 26466911; PMCID: PMC4492052. PMID: 2646691

14. Nguyen, H., Wu, H., Ung, A., Yamazaki, Y., Fogelgren, B., and Ward, W. S., “Deletion of Orc4 during Oogenesis Severely Reduces Polar Body Extrusion and Blocks Zygotic DNA Replication”. Biology of Reproduction 106: 730-740, 2022. PMID: 34977916; PMCID: PMC9040667

15. Ribas-Maynou, J., Nguyen, H., Valle, R., Wu, H., Yeste, M., Ward, W. S. “Sperm degradation after vasectomy follows a sperm chromatin fragmentation dependent mechanism causing DNA breaks in the toroid linker regions”. Molecular Human Reproduction, Aug 29, 2022. PMID: 35929777, PMCID: PMC9422300

16. Hieu Nguyen, Jordi Ribas-Maynou, Hongwen Wu, Beverly Quon, Tracy Inouye, Brienne Walker, Caitlin Langaman, Thomas TF Huang Jr., and W. Steven Ward. “Low levels of mouse sperm chromatin fragmentation delay embryo development”. Biology of Reproduction, 2023, 109: 635-643, 2023. PMID: 37658763; PMCID: PMC10651064