Medical School Hotline

Introduction

The Institute for Biogenesis Research (IBR, www.ibr.hawaii.edu) was founded in September of 2000 to advance the study of reproductive and developmental biology. The incentive for the creation of the IBR was to propagate the legacy of the University of Hawai‘i's world renowned expertise in reproductive biology largely due to the outstanding research contributions of Dr. Ryuzo Yanagimachi. Since its inception, the IBR has grown from its first founding member to 9 full time faculty and 4 associate members. The success of the institute is measured in its worldwide recognition, its success in competing for federal grant funding, and its contributions to the university in teaching and extended research support.

Legacy of Dr. Yanagimachi

The University of Hawai‘i decided to establish the IBR primarily to institutionalize the decades long research successes of Dr. Yanagimachi. He joined the University of Hawai‘i (UH) in 1965, and has remained ever since. Before coming to Hawai‘i, Dr. Yanagimachi had already distinguished himself as a leader in reproductive biology by making a major contribution to the development of techniques that would allow mammalian sperm to fertilize eggs in vitro.¹ At UH, he again amazed the scientific world by injecting a sperm head into an egg to achieve fertilization.² These two studies, supported by numerous other publications, became the basis for the two major treatments for human infertility, in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), that result in millions of babies born to infertile couples around the world. In 1997, Ian Wilmut and colleagues cloned the first mammal, Dolly the sheep,³ but this was only one animal, and the scientific community was not fully convinced it was possible to do this procedure routinely. The next year, Yanagimachi's group demonstrated a novel method for cloning mammals. They cloned 50 mice, and five generations of cloned clones.⁴ This firmly established the discovery, and now their technique is used around the world to clone animals. Dr. Yanagimachi also developed a novel technique to create transgenic mice.⁵ For these and many other discoveries, Dr. Yanagimachi was elected to the prestigious National Academy of Sciences, USA, in 2001.

The press coverage of these latter discoveries awakened the state to Dr. Yanagimachi's contributions, and the university decided to establish the IBR with some community support. The Castle Foundation provided a $1 million grant to recruit new faculty to populate the IBR, and the university contributed $5 million to construct a new 15,000 sq ft research facility in the BioMed Tower on the UH Manoa campus.

International Recognition for Reproductive and Developmental for the Biology Faculty Members of the IBR

As with any research institute, the strength of the IBR lies in its faculty members. The IBR has a particularly cohesive group with a large diversity of scientific interests and technical expertise, coupled with the common overall theme of fertilization and early development. Figure 1 depicts our current faculty members, 8 of whom are full time IBR and 3 associate members. In the fourteen years since its inception, the IBR has grown from three to twelve faculty with diverse, but related research projects. The faculty work together in various collaborations, increasing the productivity of the entire unit.

Figure 1.

Research Focus of the IBR. The figure diagrams the stages of early fertilization and embryogenesis, and the areas of research of twelve IBR faculty.

The IBR was started in September of 2000 with three faculty members and a lab manager. Dr. Yanagimachi was the founding director. He recruited Dr. Yusuke Marikawa who focuses currently on gene pathways that direct body plan formation,^6,7 and Dr. W. Steven Ward who concentrates on sperm chromatin structure.^8,9 Dr. Stefan Moisyadi was the first lab manager of the IBR, and oversaw the construction of the main facility located at 1960 East-West Rd., in the BioMed Tower on the Manoa campus of the University of Hawai‘i. The IBR leadership quickly realized that Dr. Moisyadi was more than capable of heading his own research program, which he initiated in 2004. He developed a new molecular system to create transgenic animals and has been recognized for his major contributions to the field.^10,11

Between 2002 and 2005, the IBR welcomed three additional faculty who came as postdoctoral fellows in 2000. All have made significant contributions, not only to the school, but to their areas of research. Currently, Dr. Vernadeth Alarcon, who trained with Dr. Marikawa, focuses on the earliest cell differentiation during development, the division of cells into those that will become the embryo and those that lead to the placenta^12,13 Dr. Monika Ward, who trained with Dr. Yanagimachi, developed a highly respected program that is determining the function of the genes on the Y chromosome in fertilization.¹⁴ Her group recently demonstrated that only two genes on the Y chromosome were needed for male mice to be capable of fertilization with assisted reproduction.¹⁵ Dr. Yukiko Yamazaki, who also trained with Dr. Yanagimachi, focuses on the embryonic development of sperm and oocytes^16,17 and has recently developed new techniques to culture oocytes. In 2003, the IBR recruited Dr. Richard Allsopp who is interested in telomeres,^18,19 and in stem cell therapy. He has initiated a program to test the efficacy of stem cells as a therapy for heart injury.

In 2013, the IBR recruited four additional faculty as part of an application for a NIH center grant to support the program. Dr. Alika Maunakea was newly recruited to the Department of Native Hawaiian Health. His research interest is on how epigenetic modifications affect human disease.^20,21 He is collaborating with Dr. M. Ward to test assisted reproductive techniques that might contribute to the development of epigenetic diseases such as autism. Dr. Lana Garmire is a new recruit to the University of Hawai‘i's Cancer Center whose focus is bioinformatic analysis of genomewide sequences in cancer.²² Her focus in the IBR will be the relationship between obesity during pregnancy and the generation of epigenetic mutations that lead to cancer.²³ Dr. Benjamin Fogelgren is a member of the same Department of Anatomy, Biochemistry and Physiology. He was invited to join the IBR when it became apparent that his research on cavity formation during kidney development^24,25 had direct implications for blastocyst formation during early embryogenesis. Finally, Dr. Johann Urschitz who trained with Dr. Moisyadi,^26,27 is working to use the transgenic methods developed in Dr. Moisyadi's lab as gene therapy to address the problems of fetuses of obese mothers.

Success of Grant Funding

A measure of success of any research institute is its ability to compete for grant funding to support its work. In this, the IBR is following a predictable timeline in which the funding has increased over time (Figure 2). In the first four years IBR funding averaged about $1 million per year. This reflects both the small number of principal investigators in the early years, and the early development of the younger faculty. By 2008, the IBR faculty had developed a reputation that the team could successfully compete for a large NIH center grant to support its research. This brought in $10.5 million over the next six years. It also allowed the establishment of Hawai‘i's first Transgenic Mouse facility, and the techniques for making transgenically modified mice in the IBR established important mouse models for Hawai‘i's researchers. The infrastructure of this grant established strengthened applications of IBR researchers for subsequent grant proposals. In July, 2014, the IBR was awarded a second phase of the center grant for an additional $11 million to support the IBR for the next five years. Individual faculty have also been productive in obtaining grant support for their respective research programs. In fiscal year 2013, the IBR had one fourth of all the NIH R01s in the medical school. These are the most competitive individual grants for principle investigators from the federal government, a hallmark of successful biomedical researchers.

Figure 2.

Total Grant Funding per Year in the IBR. This graph depicts all the extramural funding for which the faculty of the IBR successfully competed. The data are accurate as of August 8, 2014, and does not include additional grants that have not yet been awarded after 2014.

To date, the IBR has brought in $38.6 million in extramural grant funding. It is significant that most of this federal funding enters directly into the Hawai‘i state economy. This is illustrated in Table 1 that details the expenditure of the IBR's largest extramural award. About half of these funds will pay for salaries of employees that not only creates jobs, but contributes money into the economy. Another 30% is paid directly to the University of Hawai‘i to pay for the infrastructure that supports research. Eighty percent of the federal dollars that the IBR brings to the university goes directly into the state's economy.

Table 1.

Budget for the IBR-COBRE Phase 2 (2014–2019)

Grant Portion	Amount	Percent
Total Grant Award	$10,840,520	100%
Salary	$5,269,460	49%
Indirect	$3,390,520	31%
Direct to Hawai‘i Economy	$8,659,980	80%

The Graduate Program in Developmental and Reproductive Biology

In addition to having established a world class biomedical research unit at UH and having contributed significantly to Hawai‘i's economy, the IBR also plays a strong role in teaching. As a Research 1 university, the University of Hawai‘i at Manoa provides graduate training for Hawai‘i's citizens giving them opportunities to develop skills for high-paying, technically advanced careers. The IBR is recognized world wide for its skills in micromanipulation and mouse genetics. With the success in grant funding, the IBR decided to develop a new graduate program to train local students. In 2008, with the success of the first center grant, a unique opportunity came about to do just this. The chair of the department, Dr. Scott Lozanoff, asked the IBR to propose a reorganization of the Graduate Program in Physiology. Drs. S. Ward and Allsopp made a proposal to change the name to, “Graduate Program in Developmental and Reproductive Biology (DRB; http://www3.jabsom.hawaii.edu)”. The program has been successful in training MS and PhD. students. These graduate students are supported by teaching assistanceships that support undergraduate education at University of Hawai‘i at Manoa.

Conclusions

In the fourteen years since its inception, the IBR has become a world renowned center for biomedical research in the field of reproductive and developmental biology. The IBR also supports the educational missions of UHM and JABSOM, as well as contributing to other research endeavors throughout the state. By all measures, the institute can be counted as one of Hawai‘i's success stories.

Conflict of Interest

None of the authors identify a conflict of interest.