A recent study by researchers at the University of �鶹��ý at Mānoa and Washington State University shows how fathers pass on traits influenced by their environment to their children. The research provided new data refining the mechanistic basis of paternal epigenetic inheritance.

The team was spearheaded by Monika Ward of the (JABSOM) and Wei Yan of Washington State University, whose work offers new insight into how these hereditary signals function.

, the study challenges the idea that sperm pick up this vital environmental information while maturing in a specific part of the male reproductive system called the epididymis. Instead, researchers found that mature sperm lack the specific mitochondrial DNA (genetic material for cell energy) required to facilitate this process, suggesting the information is set earlier while the sperm is still in the testes.

How testes help pass on traits

To test this, researchers fed male mice a high-fat diet. They then used a specialized fertilization technique to create offspring using both early-stage sperm from the testes and fully mature sperm. They discovered that the early sperm passed on traits from the father’s diet just as effectively as the mature sperm did.

“This work is a perfect example of how assisted reproduction technologies can be used to advance understanding of key processes in male reproduction,” said Ward, a researcher in the and professor of anatomy, biochemistry and physiology.

Related UH News story: UH researchers advance study of key male fertility gene

By using a direct injection technique with early-stage sperm, the team proved that sperm do not need to mature in the epididymis to pass on environmental information.

The study also clarified the amount of mitochondrial DNA in sperm. By testing sperm at various stages, the team confirmed that this material is progressively removed during development, leaving mature sperm almost entirely without it. They also found that small RNA, which carries genetic information, is primarily set during development in the testes.

The findings support a framework in which environmentally responsive molecular information is programmed during sperm development in the testes and later delivered to the egg by mature sperm depleted of mitochondrial DNA.

“The founder of our institute, Ryuzo Yanagimachi, was a pioneer who first developed many of the techniques used in modern IVF,” said Ward. “This study is a great example of how his legacy and our expertise continue to lead to new scientific discoveries.”

New mouse models to study a key male fertility gene, providing insights that could help scientists understand and eventually treat male infertility, were developed by researchers at the . The study, published in , builds on years of research into how this gene functions in male reproductive cells.

The work, led by Professor Monika Ward of the and the , focuses on the Y chromosome gene ZFY, which is critical for male fertility. In earlier studies, the team demonstrated that male mice lacking both copies of Zfy were completely infertile and showed widespread disruption of genes involved in sperm development and cell survival.

New tools to track ZFY proteins

In the newly accepted study, the team used CRISPR–Cas9 genome editing to add molecular “tags” to the two mouse versions of Zfy, known as Zfy1 and Zfy2. These tags make it possible to detect, isolate and study the proteins in unprecedented detail.

Related UH News story: Missing Y gene linked to male infertility

Using the tagged mouse models, the researchers were able for the first time to identify which male germ cells produce Zfy1 and Zfy2 proteins and at what levels.

“We now know which male germ cells express which Zfy proteins, and how strongly,” said Ward.

Because ZFY is thought to act as a transcription factor—switching other genes on and off—the new models could help identify which genes it regulates, offering critical insights that may one day guide diagnosis and treatment of male infertility.

“We have been after the Zfy genes for a long time! We knew how important Zfys are for male fertility for quite a while but were unable to learn how exactly they work,” Ward said. “The new mice represent a much-needed tool to continue the investigations to determine how Zfy controls spermatogenesis.”

Read more at .

From China to �鶹��ý, Hongwen (Winnie) Wu has turned a career as a board-certified obstetrician-gynecologist (OB-GYN) into groundbreaking reproductive biology research. This fall, she earned her PhD in the Developmental and Reproductive Biology graduate program at the at the University of �鶹��ý at ����ԴDz�, becoming the first Kosasa Graduate Student Assistantship recipient.

The prestigious assistantship, funded by Thomas Kosasa of Pacific IVF and a professor emeritus at JABSOM, was created to strengthen connections between the (YIBR), the OB-GYN Department, and Pacific IVF.

“Through a dynamic approach, I aspire to significantly contribute to improving individual patient health and advancing the broader landscape of women’s health research,” said Wu, who joined JABSOM’s Developmental and Reproductive Biology program from China in fall 2019.

Advancing fertility research and education

As a PhD student, Wu carried out her research in Steve Ward’s lab at YIBR, focusing on female fertility. She studied the protein EXOC5 in ovarian aging and discovered it is essential for normal egg development, with its absence leading to ovarian failure.

During her time at JABSOM, Wu co-authored five manuscripts and presented her work at seven local and four national conferences, including the Society for the Study of Reproduction and the Society for Reproductive Investigations. She received the 2024 ARCS Award in Medicine, served as a teaching assistant, volunteered at research events, and was a visiting scholar at Northwestern University.

Her long-term goal is to remain in �鶹��ý as a research physician/scientist, blending cutting-edge research with clinical expertise to advance women’s healthcare.

“Winnie’s performance as the first Kosasa Assistantship-supported DRB student has been exemplary,” said Monika Ward, interim director of YIBR. “She contributed research of relevance to all four parties: DRB, YIBR, OB-GYN and Pacific IVF.”

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Members from the University of �鶹��ý at ����ԴDz� (SOEST) and (JABSOM) were featured in the new documentary , which premiered at the 45th �鶹��ý International Film Festival (HIFF) on October 23, 2025.

Contributing to the film were several leading oceanographers from SOEST including Jeff Drazen (professor), Jamison Gove (alumni and research affiliate), Nikolai Maximenko (senior researcher), Margaret McManus (chairwoman of the Department of Oceanography and director of the Uehiro Center for the Advancement of Oceanography), and Jonathan Whitney (alumni, former postdoctoral researcher, and research affiliate); and a scientist at JABSOM’s , Rodrigo Weingrill. The �鶹��ý����ԴDz� experts joined filmmakers, professional athletes, and community partners at the festival for the premiere of KULEANA.

Weingrill was selected for the film for his research on microplastics, including studies showing an accumulation of microplastics in human placentas in �鶹��ý. The film highlights that plastic pollution has become a human health concern.

A central scene follows professional surfer Kai Lenny as Weingrill’s team tests his blood, finding 33 microplastic particles in just 2 milliliters. With an average adult having about five liters of blood, Weingrill estimated that Lenny would have “around 80,000 particles in all his blood.”

Related UH News story: Rise of microplastics discovered in placentas of �鶹��ý mothers

“I think the message is to educate our communities to prevent this exposure,” Weingrill said. He suggested making small lifestyle changes such as using glass or stainless-steel containers instead of plastic, to reduce how much plastic we take in every day.

Reflecting on his experience being featured in the film, he added, “I never expected that, I never wished that, to tell you the truth. I always wanted to do good science to help people.” He credited collaborators Johann Urschitz, Men-Jean Lee, Steve Ward and the Department of OB-GYN & Women’s Health for supporting the research.

“We’re trying to do something good for everybody and that’s the everyday goal—to help our communities, to help our people, to have a healthier life, live longer and have a really happy everyday routine,” he said.

KULEANA was directed and produced by Georgia Scott and narrated by Woody Harrelson. HIFF will also screen the documentary on November 1, at and on November 9 and 15, on Maui.

“KULEANA powerfully captures how plastic pollution is infiltrating the lives of ocean animals, with �鶹��ý standing at an epicenter of this global crisis,” said Whitney, marine ecologist at NOAA, who co-led a study with Gove and McManus showing that prey-sized plastics are invading larval fish nurseries. “Our research revealed an invisible threat at the foundation of ocean food webs, and it’s an honor to collaborate with talented filmmakers who can bring these scientific stories to life for the world to see.”

Read more at and .

University of �鶹��ý at ����ԴDz� scientists have uncovered a direct link between a missing Y chromosome gene and male infertility. Their new research reveals that deleting this single gene in mice not only caused infertility but also disrupted hundreds of other genes vital for healthy sperm. The findings, published August 27 in , offer significant implications for understanding reproductive health.

The role of Zfy

The study, led by Monika Ward of UH ����ԴDz�’s and the (YIBR), focused on the Zfy gene, found on the Y chromosome in both humans and mice. In mice, there are two versions of this gene: Zfy1 and Zfy2.

Using CRISPR gene-editing, the team created mice missing one or both versions. Males without both, known as Zfy double knockouts, were completely infertile, with severely abnormal or absent sperm.

“This work really pushes forward our understanding of how this important Zfy gene works,” said Ward. “We identified pathways and other genes that are affected and we can now study how exactly Zfy regulates them.”

To continue investigations, the researchers turned to assisted reproduction techniques pioneered at UH, including intracytoplasmic sperm injection (ICSI) and round spermatid injection (ROSI). This allowed them to examine the molecular consequences of Zfy loss.

When one gene disrupts hundreds

The results revealed that without Zfy, hundreds of genes became misregulated—some too active, others too weak. Many of these genes are responsible for sperm production, DNA packaging, and cell survival.

As a result, sperm precursor cells in the testes died off early, and the sperm that did form carried fragile DNA that wasn’t properly condensed.

Student-assisted research

Ward also highlighted the contributions of students. The study’s first author, Hayden Holmlund, completed his PhD at UH and is now a postdoctoral fellow in California. Undergraduate student Benazir Yarbabaeva also played a role and has since joined the graduate program to continue her research.

The project highlights YIBR’s collaborative mission, with contributions from colleagues in France and England.

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Native Hawaiian scientist Alika Maunakea of the University of �鶹��ý at ����ԴDz� (JABSOM) has spent more than 20 years studying epigenetics–—how environment shapes health across generations. With colleague Monika Ward of JABSOM and the , they examined how maternal obesity before pregnancy may influence autism risk.

Related UH News story: UH study links maternal obesity to autism-like traits in offspring

Q: What motivated this research, and what did you discover?

We were struck by the worldwide rise in autism and by data showing that mothers who are obese face a 50–60% higher risk of having a child with autism. What wasn’t clear was when that risk takes hold—is it during pregnancy or even before? In our study, we found that maternal obesity before conception was enough to increase the likelihood of autism-related traits in offspring, at least in our mouse model. That finding points to an important window of time that hasn’t received much attention.

Q: How confident are you that these findings translate to humans?

While our work was done in mice, many of the same genetic pathways we studied are conserved in humans. What’s striking is that autism-related genes known to raise risk in people were also affected in the mouse model, not by mutations but by epigenetic changes that altered gene expression. So while it’s not proof, it strongly suggests that similar mechanisms could be at play in humans, and that gives our findings real relevance.

Q: Does obesity guarantee autism risk for a child?

No, it’s important to stress that obesity is not a determining factor. In our study, even among mice with obese mothers, about 60% developed normally. What maternal obesity does is raise the risk, which is very different from guaranteeing an outcome. That nuance matters, because it shows there’s room to intervene and reduce risks rather than assuming outcomes are fixed.

Q: What does this mean for timing—before vs, during pregnancy?

We’ve long known pregnancy is a critical period, but our study highlights that the preconception window is just as important. Health status before pregnancy can shape risks for children, not just for autism but also for other chronic conditions. This means lifestyle changes made even before planning a pregnancy, such as improving diet, exercise and overall metabolic health, may help improve outcomes for both parent and child.

Q: Is it ever too late to make lifestyle changes?

No. The message is that any step to improve health is worthwhile. Even outside the context of pregnancy, better diet and exercise lower risks for chronic disease. But when we’re talking about planning a family, those same changes may also lower risks for future children. So the preconception period is a powerful window of opportunity, but positive changes at any stage are valuable.

Q: Where does the research go from here?

The next step is to see whether improving health before conception can actually lower the autism risk we observed, and whether those benefits extend across multiple generations. We also found that male offspring were more affected than females, so we want to explore why that is and how long these effects last. These are unanswered questions with big implications for human health.

Q: How should the public understand this research?

Most importantly, this isn’t about blame. Obesity is shaped by many factors, like access to healthy foods, safe places to exercise, and healthcare resources. Our work shows opportunities where supportive policies, healthcare guidance, and community programs can make a difference. Beyond autism, improving metabolic health before conception is simply good practice for lifelong health, both for parents and for their children.

Q: How does Native Hawaiian knowledge influence your work?

As a Native Hawaiian epigeneticist, I draw inspiration from our ʻike kupuna (ancestral knowledge). For centuries, Hawaiians understood that pregnancy timing and environment shape a child’s health. For example, a saying advises strengthening the unborn child through diet and herbal remedies, an early recognition that what mothers do before and during pregnancy can affect future generations. Our research in epigenetics reflects that same idea: the environment can influence health outcomes long before birth.

Researchers at the University of �鶹��ý at ����ԴDz� (JABSOM) have uncovered a connection between a mother’s weight before pregnancy and autism-like behaviors in her offspring.

Published in , the study marks a significant advance in understanding how early life factors influence brain development.

Led by Professors Alika K. Maunakea and Monika Ward from JABSOM’s and the (YIBR), the research shows that maternal obesity triggers metabolic shifts that cause lasting epigenetic changes in a mother’s eggs. These changes are passed on to the developing embryo and affect genes involved in brain development, including Homer1, a protein important for regulating synaptic signaling, learning, memory and response to neural activity.

In male offspring, researchers identified increased levels of a specific Homer1 gene isoform that is known to interfere with neural connections and is associated with behaviors linked to autism spectrum disorder (ASD).

“This work highlights how a mother’s health prior to pregnancy, not just during gestation, can shape her child’s brain development in profound ways,” said Maunakea. “We were surprised to find that even without direct maternal contact after conception, these epigenetic imprints from the egg carried enough weight to alter behavior.”

Clearer understanding through IVF model

To isolate the effects of pre-pregnancy obesity from those during gestation, the researchers used an in vitro fertilization (IVF) and embryo transfer model. This approach allowed them to study early epigenetic programming more precisely.

Behavioral assessments of adolescent male mice revealed impaired social interactions and repetitive behaviors. These traits, which mirror characteristics of ASD, were linked to altered gene regulation in the brain.

“This discovery exemplifies the core mission of the YIBR,” said Ward. “By leveraging our institute’s expertise in developmental biology, reproductive science and epigenetics, we are beginning to understand how early-life programming can ripple through generations.”

With both obesity and ASD rates increasing worldwide, the findings may lead to early interventions, potentially even before conception. Future research may explore nutritional or pharmacological strategies to reverse or reduce these effects.

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The University of �鶹��ý at ����ԴDz�’�� Biomedical Sciences Building (Biomed) was heavily damaged by the October 30, 2004 flood, which hit the campus after intense, short-term downpours. The flooding destroyed years of vital medical research and contributed to an estimated $80 million in losses across campus. Over the past two decades, the university has worked to rebuild and improve, reflecting the resilience of the researchers and staff who were affected.

Impact on research, community

Biomed housed many faculty, staff and researchers from the (JABSOM) before the move to the Kakaʻako site, and the flood led to the loss of irreplaceable research samples as freezers thawed due to power failures.

“All the freezers were starting to thaw, mud was about four to five feet high, and the drywall was completely soaked,” recalled Sam Shomaker, now dean of JABSOM, who was vice dean at the time. “We brought in 20 portable generators and ran extension cords through the upper floors to power the freezers.”

It was like a hurricane raging through ����ԴDz�.
—Stefan Moisyadi

Shomaker was out to dinner when the flood hit. “A faculty member called me from his lab bench, where he was standing with his dog as the flood tore through the building. I rushed to campus, but the entrance was blocked by police. I later learned they had to rescue him and a student by raft,” he said.

Among those affected was the late Ryuzo Yanagimachi, a pioneer in cloning research, whose (IBR) labs were located on the ground floor. “It was like a hurricane raging through ����ԴDz�,” said Associate Professor Stefan Moisyadi, a member of Yanagimachi’s team. He recalled the urgency in saving Cumulina, the world’s first cloned mouse now part of the Smithsonianʻs collection, by moving her to the second floor to escape the rising floodwaters.

Related: Hamilton Library 20 years after the UH ����ԴDz� flood, October 2024

Despite the devastation, IBR was one of the first labs to recover, rebuilding within six to eight months. “We recovered nicely compared to others, but it was a shattering experience for all of us,” said Moisyadi.

Shomaker reflected on the collective efforts that followed. “What I took away from that experience was seeing how tightly knit our ʻohana at JABSOM was—and still is,” he said.

The university community worked tirelessly to preserve research and relocate displaced faculty, with new lab spaces opened at the newly completed JABSOM ʻohana site in 2005. A large generator was also brought in from the West Coast to support ongoing research.

“We had daily committee meetings to assess recovery progress. It was a remarkably complex process, but it demonstrated the resilience of our community,” Shomaker said.

Progressing from experience

Although most of Biomed has been rebuilt, the memories of the flood still serve as a reminder of the importance of preparedness. “Every time it rains, our janitors place sandbags around the building,” Moisyadi noted. He also stressed the need for regular maintenance of trees along ����ԴDz� Stream to prevent future flooding.

Currently, all research projects are located on the second floor, while the offices, library, and the lunchroom are on the first floor. “If another flood occurs, there is little we can do, but we are better prepared because of what we already went through,” Moisyadi added.

Read more about UH ����ԴDz�’s flood recovery efforts at Hamilton Library.

Ryuzo Yanagimachi’s legacy lives on through his groundbreaking work and the personal stories shared by those who knew him best. Known as the “Father of IVF,” Yanagimachi, a pioneering scientist at the University of �鶹��ý at ����ԴDz�’s (IBR), part of the (JABSOM), died in 2023, shortly before receiving the Kyoto Prize in Biotechnology and Medical Technology.

Related UH News story: In memoriam: Ryuzu Yanagimachi, cloning pioneer

Kyoto Prize recipients give speeches at three venues: a grand ceremony in Kyoto, the University of Oxford, and University of California, San Diego (UCSD), where 200 local high school students attend. At UCSD, Steven Ward, who was recruited by Yanagimachi and has served as the IBR director since 2009, spoke on behalf of his late mentor.

“I had known the man for 28 years and worked side by side with him every day for 23. He had 50 years of science and published 400 papers,” Ward said. “I could have spent a week talking about what he did and what he contributed to the field.”

Rather than focusing on Yanagimachi’s scientific achievements, Ward shared personal stories. He remembered his mentor through an oral history, drawing from personal experiences and Life in Science articles Yanagimachi had written over the years.

“Yana was famous enough that people wanted to know his life story in written print. You don’t see this very often,” Ward said. “Those were really interesting because I got a real insight into why he was doing experiments.”

Impact beyond research

Yanagimachi’s influence extended beyond his research. Ward explained that his cloning breakthroughs likely helped save UH’s medical school from closure. In 1999, the UH Faculty Senate voted to merge the school with the School of Public Health.

“When I moved here in 2000, they were talking about closing the medical school. Then Yana’s cloning stuff came up and lit the world on fire,” Ward said.

Ward also emphasized how Yanagimachi’s mentorship encouraged innovation. “He gave his researchers freedom,” Ward said, recalling how Yanagimachi fostered new ideas, including the “Honolulu method” of cloning. “He believed in letting us experiment and explore.”

Ward’s oral history approach was well-received and sparked discussions about changing how future Kyoto Prize speeches are structured.

As JABSOM continues to mourn the loss of their pioneer, Ward intends to continue passing along the history of one of the most influential scientists at UH.

“There are certain things you’ll never get written down that you only have from these oral histories. So it’s important for people to talk to each other,” he said. “It’s important for the younger generation to talk to the older scientists in the community so that they get those things that are never written down.”

In recognition of his contributions, IBR will be renamed the “Yanagimachi Institute for Biogenesis Research,” and a symposium in his honor is planned.

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Researchers at the University of �鶹��ý at ����ԴDz�’s (JABSOM) have achieved a breakthrough in gene editing that could revolutionize the treatment of genetic diseases such as hemophilia. The new technique enables a faster, safer and more efficient delivery of healthy genes into the body, potentially addressing hundreds of genetic conditions.

This research was published in . The research team is led by Jesse Owens, along with Brian Hew, Ryuei Sato and Sabranth Gupta, from JABSOM‘s and Cell and Molecular Biology Department.

Traditional gene-editing methods, while promising, often struggle with unintended DNA damage because of difficulties in inserting large genetic material, such as whole genes. However, the research team’s method overcomes these challenges by utilizing a specially engineered “super-active integrase” (nucleic acid processing enzyme) that can insert therapeutic genes into the genome with precision and efficiency—achieving success rates of up to 96%.

“It’s like having a ‘paste’ function for the human genome,” said Owens. This advancement allows for the careful insertion of healthy genes without causing DNA breaks, offering hope for more effective and affordable treatments for genetic disorders.

“This could lead to faster and more affordable treatments for a wide range of diseases, potentially impacting hundreds of conditions with a single faulty gene,” added Owens.

Accelerating advanced medical treatment

Beyond gene therapy, this new technique has broader implications for medicine. It can significantly speed up the development of cell lines used in producing therapeutic proteins, which traditionally involves a time-consuming process of randomly inserting genes and then searching for cells that produce the desired proteins.

Owens’ method streamlines the process, delivering genes directly to the desired location in the genome, making the development of biologics and advanced therapies, such as antibodies, more efficient.

“JABSOM takes pride in nurturing talented researchers like Jesse Owens, whose work has the power to create a global impact,” said Sam Shomaker, JABSOM dean. “This research, conducted in our lab in the middle of the Pacific, has the potential to significantly improve the way we treat genetic diseases.”

The JABSOM team continues to explore how this technique can accelerate the development and manufacture of life-saving therapeutics. Owens founded , a 501c3 nonprofit aimed at supporting local research in genetic engineering in �鶹��ý.

A placenta (commonly known as the “afterbirth” or “ʻiewe” in Hawaiian) is a temporary organ which connects the mother to the fetus via the umbilical cord. Its purpose is to deliver nutrients and oxygen to the fetus while serving as a barrier to prevent infections or viruses from entering the developing fetus.

A new study by researchers at the (JABSOM) at the University of �鶹��ý at ����ԴDz� and examined placentas donated by women who delivered in �鶹��ý from 2006 to 2021, and found the presence of microplastic particles in the placenta.

Microplastics are visible to the naked eye, and examples can range from the plastic beads once found in exfoliating soaps, to particles from disintegrating plastic bags, to bits of plastic found in microwavable containers which are then inadvertently consumed by humans.

“We were shocked that these little pieces of plastic were getting across the mom’s gut and landing in the placenta,” said Men Jean Lee, an obstetrician and researcher at JABSOM and Kapiʻolani Medical Center. Lee, Rodrigo Weingrill and Johann Urschitz from UH ����ԴDz�’�� co-authored the research recently published in .

The researchers collected and studied 10 placentas in 2006, 2013 and 2021 and found the presence of microplastics grew each year.

• In 2006, 6 of the 10 placentas contained microplastics.
• In 2013, microplastics were found in 9 of the 10 placentas.
• In 2021, researchers found microplastics in all 10 placentas.

“We believe that the plastics may be floating around in food or being inhaled. It’s coming through our digestive fluids or lungs, and the particles are getting absorbed through the gut and traveling through the bloodstream, and then somehow collecting in the placenta during pregnancy,” Lee said. “The big question is, as it’s traveling through the placenta, can it get through the umbilical cord and then to the baby? We don’t know that right now.”

Link to global plastic production

We know that the rise in microplastics found in the placentas of �鶹��ý mothers corresponds with the skyrocketing levels of global plastic production.

According to the Journal of Hazardous Materials, more than 6,000 megatons of plastic were produced in 2020. Less than 2,000 megatons were produced in 2000.

The big question is, as it’s traveling through the placenta, can it get through the umbilical cord and then to the baby?
—Men Jean Lee

Lee believes H�鶹��ý‘s remote location creates an added dependency on plastic.

“We’re the world’s most remote population center or island chain. We’re 2,300 miles from California and 4,000 miles from Japan,” Lee said. “For daily conveniences, we commonly use plastic wrap, plastic containers, plastic bags and single use water bottles.”

She suggests �鶹��ý‘s location in the center of the Pacific Ocean, tropical climate, and lack of recycling centers can exacerbate how these plastics are disintegrating or breaking down.

“The incineration of garbage, landfills and marine pollution affect our communities. When trash is being burned, dust particles are released, and can spread into the air we breathe,” Lee said. “In fact, we are concerned about how the debris from the recent Lahaina fires may contain microplastics and other chemical toxins in the remains of the fires. Meanwhile, we already know that sunlight, heat and salt can speed up the breakdown of these everyday plastics. I’ve noticed plastic bags, even shoes, wear out quickly in �鶹��ý and turn to dust. I never experienced this when I was living back in New York.”

Can microplastics enter the fetus too?

Lee and the JABSOM researchers will continue their research, now focused on seeing if the microplastics can pierce the protection of the placenta and enter the fetus before birth.

“We’re not trying to scare people,” Lee said, but acknowledges there are other questions that still need to be answered. “What are the sources of maternal microplastics? What are the plastics doing in the mother’s body and the placenta? Are they benign, or are they crossing over to the fetal side into the umbilical cord that is connected to the baby? If they are getting to the other side, are they affecting fetal growth and what happens to the baby when he/she grows up?”

Ryuzo Yanagimachi, whose pioneering contributions to reproductive biology and cloning have impacted millions of people and allowed families to grow, died on September 27, at the age of 95, the University of �鶹��ý at ����ԴDz� announced.

The renowned researcher began at UH ����ԴDz� in 1966 as an assistant professor at JABSOM‘s Department of Anatomy and Reproductive Biology. Yanagimachi, or “Yana” as he was affectionately called, pioneered cloning and made numerous breakthroughs in mammalian fertilization and other fertilization techniques, such as intracytoplasmic sperm injection (ICSI). These techniques are used around the world in human infertility clinics.

“Dr. Yanagimachi’s research into cloning and IVF (in vitro fertilization) changed the world,” said Interim Dean Lee Buenconsejo-Lum. “Yana’s breakthroughs in cloning and IVF helped make the world a happier place for millions of families. His legacy is etched in history and at the University of �鶹��ý John A. Burns School of Medicine. We are so honored that he was part of our ʻohana for so many years.”

Cloning breakthrough

In addition to his in vitro fertilization and intracytoplasmic sperm injection achievements, in 1997, at the age of 69, Yanagimachi cloned the world’s first mouse. This groundbreaking research was published a year later in the journal Nature, detailing how he removed the nucleus from a somatic cell (any cell in a living organism, other than reproductive cells) and injected it into an egg that also had its nucleus removed. The egg, bathed in a chemical solution and cultured, developed into an embryo, which was then implanted into a surrogate and allowed to develop. It is now known as the “Honolulu Technique.”

The first mouse born through the Honolulu Technique was named Cumulina. It symbolized the incredible possibilities unlocked by Yanagimachi’s pioneering work. That mouse is now in the Smithsonian in Washington D.C.

Contributions earn researcher accolades

His 38-year tenure and 18 years as professor emeritus were marked with many global breakthroughs.

Related: Yanagimachi wins Kyoto Prize for pioneering fertilization research, June 2023

Most notably, Yanagimachi was honored this year with the Kyoto Prize, an international award presented to individuals who have made significant contributions to science and technology, as well as the arts and philosophy. Many compare it to the Nobel Prize. Yanagimachi was recognized in the Biotechnology and Medical Technology category for his significant contributions to the development of essential assisted reproductive technologies in modern society through both basic research and technological development. He was scheduled to accept the award in November 2023.

When the award was initially announced Yanagimachi humbly said, “Although I was rarely directly involved in clinical investigations, I am very happy that some of the work we did played a role in bringing joy to many infertile couples.”

Yanagimachi received numerous awards, including the 1996 International Prize for Biology, Japan’s highest scientific award, and the 1999 Carl G. Hartman Award, the Society for the Study of Reproduction’s greatest honor. He was inducted into the National Academy of Sciences in 2001.

Shaping the future of research, mentoring leaders

In 2000, Yanagimachi founded and directed UH’s (IBR). The institute, devoted to studying embryogenesis, stem cell development, and transgenesis technology, would continue to push the boundaries of science. The faculty, staff and students cloned the first male animal from adult cells. In 2004, Yanagimachi’s team used intracytoplasmic sperm injection techniques to produce pups from an infertile male mouse. These achievements were critical moments in advancing research in human infertility.

In 2005, Yanagimachi retired, but continued active research. His passion for reproductive biology and cloning never waned.

“He was an innovative scientist and a great mentor. He was an inspiration to the faculty, staff, post-doctoral fellows, and students. He will always be part of our ʻohana,” JABSOM Associate Dean for Research Mariana Gerschenson said.

Throughout his illustrious career, Yanagimachi would also remember to pave the way for future scientists. Remembering his struggles breaking into the research field, Yanagimachi mentored and inspired up-and-coming researchers such as Monika Ward.

“My journey began in 1999 when I moved from Poland to �鶹��ý as a graduate student,” Ward said “I wanted to work in Dr. Yanagimachi’s lab, but he didn’t have a spot for me at the time. He encouraged me to write for fellowships and grants. After writing for four or five grants, he was impressed with my determination, and the following year, I got hired, Yana had a policy of giving his postdoctoral fellows two days a week to pursue their own ideas. This encouragement to pursue other research venues resulted in the first cloned mouse by his postdoc Teruhiko Wakayama, who used the lab’s techniques to improve on cloning.”

Related: Renowned fertility researcher celebrated at inaugural symposium, August 2018

The current director of IBR, W. Steven Ward, said that IBR has flourished because of Yanagimachi’s initial leadership and continued example of excellence over the past 23 years of its existence.

“The IBR is populated by scientists who were trained by Yana, or recruited by him to join the work,” Ward said. “It is now a well established research institute world-renowned for its work on reproductive and developmental biology. Throughout his tenure at the IBR he was a constant source of possible new projects and wealth of instant knowledge of the field.”

Ryuzo Yanagimachi, professor emeritus of the University of �鶹��ý at ����ԴDz� (JABSOM) is one of three international recipients of the prestigious . Yanagimachi is the winner in the Biotechnology and Medical Technology category for the impact he’s had on millions of families worldwide through his pioneering work on mammalian fertilization, which led to in vitro fertilization (IVF) advances, giving hope to couples who otherwise would be unable to have children.

Yanagimachi said in a statement, “When I began working as a postdoctoral fellow with Dr. M. C. Chang (the father of mammalian in vitro fertilization), I was interested in analyzing the entire processes of mammalian fertilization.” 

After becoming a faculty member of UH, he and his team worked on every step of fertilization by using various animals and techniques. 

“Microsurgery was one of the techniques we used to understand ‘hidden’ potentials of sperm and eggs. Many years later, clinicians found that microsurgical injection of a single sperm into an egg is most effective when there are male infertility issues. Although I was rarely directly involved in clinical investigations, I am very happy that some of the work we did played a role in bringing joy to many infertile couples,” he said.

Kyoto Prize officials wrote that Yanagimachi demonstrated a method for in vitro fertilization in mammals, expanded our insights into the fertilization process and further developed the microinjection technology by innovating the intracytoplasmic sperm injection (ICSI). He has made significant contributions to the development of essential assisted reproductive technologies in modern society through both basic research and technological development.

Cumulina, the first cloned mouse and the first cloned mammal in the United States developed by Yanagimachi and his team, was recently sent to her new home at the renowned Smithsonian’s National Museum of American History in Washington, D.C.

Yanagimachi joined UH in 1966. He was an anatomy and reproductive biology professor at JABSOM and founded the (IBR) in 2000. He directed the IBR until 2004. It remains one of the best places in the world to learn about ICSI. He continued teaching until becoming emeritus in 2006. In addition to the Kyoto Prize, Yanagimachi is the recipient of the 1996 International Prize for Biology, Japan’s highest scientific award, and the 1999 Carl G. Hartman Award, the Society for the Study of Reproduction’s greatest honor. He was inducted into the National Academy of Sciences in 2001.

More on the Kyoto Prize

The Kyoto Prize is an international award presented to individuals who have made significant contributions in the fields of science and technology, as well as the arts and philosophy. Each laureate is presented with a diploma, a Kyoto Prize medal and prize money of 100 million yen ($704,840 USD) per category.

Alongside Yanagimachi, mathematician Elliott Lieb from Princeton University and artist Nalini Malani from Pakistan are the other 2023 Kyoto Prize winners.

Nearly 25 years after her birth made international headlines, Cumulina, the first cloned mouse and the first cloned mammal in the United States recently made the trek to her new home in the renowned Smithsonian’s in Washington, D.C.

The most celebrated mouse in scientific history was named for the cumulus cells whose nuclei were used to clone her. Cumulina was created in a lab in 1997 using the distinctive “Honolulu Technique” developed by an international team led by Ryuzo Yanagimachi at the UH ����ԴDz� . Yanagimachi’s work helped lay the groundwork for in vitro fertilization in the early 1960s. Although Yanagimachi officially retired in 2005, he continues to be an active researcher at UH ����ԴDz� (IBR), which he founded.

“I view Cumulina as being an ambassador to the world for the biomedical research that’s done at the University of �鶹��ý. The University of �鶹��ý is a world-class Research 1 university. The discovery that a mouse could be cloned over and over again happened here before it happened anywhere else in the world,” said W. Steven Ward, director of the IBR and JABSOM professor.

Cumulina lived to a ripe age of 31 months, equivalent to age 95 in human years. She died of natural causes in 2001 and until she was donated to the museum, had been kept at the UH IBR, part of JABSOM.

“The fact that the Smithsonian Institute so eagerly accepted this gift is confirmation of the place in history that the discovery has. We are thrilled that the University of �鶹��ý will now be recognized in the nation’s flagship history museum as having made a major discovery in biomedical science,” said Ward.

Along with Cumulina, the museum also acquired a sheet of paper streaked with the mouse’s footprints, made on her second birthday, which speaks to the research team’s excitement about the mouse’s normal aging process.

“Cumulina is a wonderful addition to our collection,” said Curator Kristen Frederick-Frost. “This tiny mouse will help our audiences explore complex topics, from the science of making copies of organisms to the ethics of doing so. When Cumulina was born, people wondered what, or who, was next. We still wonder. She is a part of the past that pushes us to consider the possibilities of the future.”

Smithsonian magazine spotlight

Like a celebrity, Cumulina was greeted in her new hometown with a special photoshoot courtesy of . She’ll be featured in the . In D.C., she will be preserved in the museum’s Medicine and Science Division.

“I’m happy that more people can see her than here at IBR… It’s very good for us and for Cumulina too,” said Yanagimachi.

While the museum is exploring future display opportunities, details about Cumulina will be available on the museum’s website and in the American Treasures column of the Smithsonian Magazine. Cumulina was the first mammal to be cloned more than once and for several generations. In fact, the Yanagimachi Laboratory produced more than 50 carbon-copy mice using what was thought to be a more reliable cloning technique than the one used to create Dolly the Sheep. The clear reproducibility of the Honolulu Technique for cloning mammals convinced the world that cloning was real.

This work is an example of UH ����ԴDz�’s goal of (PDF), one of four goals identified in the (PDF), updated in December 2020.

When it comes to those who have been infected with SARS-CoV-2, the virus that causes COVID-19, University of �鶹��ý at ����ԴDz� researchers are at the forefront of exploring how differences in immune health might explain why some individuals recover without serious medical complications while others do not.

A is recruiting those who have tested positive for the coronavirus within 60 days of diagnosis to donate weekly blood samples up to six times. Researchers said this baseline data will aid in designing strategies to mitigate the impacts of COVID-19 on severity and mortality, particularly among those who are more vulnerable.

Study goals

The goal of this study is to “understand the natural progression of antibodies that your body produces to fight COVID-19, so the information can help others who get infected in the future,” said principal investigator Ruben Juarez, associate professor in the ’ economics department and a research fellow in the . “As we reopen the state, we expect to see a greater strain on the healthcare system and likely new cases with severe complications.”

“Beyond the known epidemiologic risk factors that indicate who may be at a higher risk for these complications, our research will allow us to improve on this prediction by incorporating information on individual immune response, where even seemingly healthy individuals may struggle to handle the virus and may need to be hospitalized if this response is not robust enough,” added Juarez, an economist working on social and economic networks. “Study results may inform policy decisions that are more targeted at the individual level to prevent the onset of these medical complications that would also tax the healthcare system.”

The study’s other principal investigator is Alika Maunakea, an associate professor at the ’s Department of Anatomy, Biochemistry & Physiology and the Institute for Biogenesis Research.

“Another goal that we hope to achieve with this study is an enhanced understanding of the biological and socioecological interactions that enable individuals and communities to be more resilient against COVID-19,” Maunakea said.

While Native Hawaiians make up 21 percent of the state’s population, recently disaggregated data from the �鶹��ý State Department of Health indicate that 13 percent of all COVID-19 cases are among Native Hawaiians. This contrasts with Pacific Islanders who account for 14 percent of the cases while only comprising 4 percent of the population. Likewise, Filipinos account for 21 percent of the cases while comprising 16 percent of the population.

“Although there are certainly disparities in the infection rate of COVID-19 in the state with some populations disproportionately affected, this data may also indicate potential resilience within the Native Hawaiian community,” said Maunakea, an expert in epigenetics and health disparities research. “By recruiting a diverse cohort of individuals recovering from COVID-19, we will be able to understand the sociobiological mechanisms underlying this resilience, and learn from our communities how best to mitigate this crisis while averting severe health outcomes among our most vulnerable. We are reaching out to the community to help us understand this problem more comprehensively, so we can collectively identify the best ways to overcome this challenge that we all face.”

How to participate

For more information about the study or to enroll if recovering from COVID-19, contact the study coordinator by phone/text at (808) 989-2043 or email covid19hi@gmail.com. This study is supported in part by the �鶹��ý Resilience Fund at the �鶹��ý Community Foundation.

—By Lisa Shirota

The University of �鶹��ý at Mānoa has received a $5.3 million grant to continue research at the laboratory that became world-famous for producing mice and other animals that glow green under ultraviolet light. This grant will allow the John A. Burns School of Medicine (IBR) to produce transgenic mice for other researchers seeking medical cures at UH.

The mouse and its pups glowed green because jellyfish genes had been inserted into a mouse embryo to demonstrate the lab’s successful technique for inserting DNA from an unrelated organism into that of another animal. The first green mouse was born, and then she transferred the glowing gene to her pups.

“All along, we’ve been developing new technologies to make us even better,” said Steven Ward, IBR director. “With this grant, we’ll be able to build on our previous 10 years of research to provide genetically altered mice for anybody at UH. These are models that scientists can use for their research—mice with specific diseases or with a certain gene missing or with a gene present so the researchers can see what they can do with it.”

Since mice are the closest animals to humans for biological testing, Ward said, making better mouse models allows scientists to advance cures.

• Read more about the Institute for Biogenesis Research at UH News

This is the third consecutive five-year funding award the IBR has been selected to receive.

The federal funding from the National Institutes of Health’s National Institute of General Medical Sciences will support collaborations between IBR, part of the UH Mānoa , and its reproductive biology departments of and .

—By Tina Shelton

, known by colleagues as “Dr. Yana,” is an internationally-renowned fertility researcher, whose development of the “Honolulu Technique” to create the world’s first cloned mouse brought international acclaim to the . In August 1998, the achievement was featured in news articles around the world.

On August 27—20 years later and on Yanagimachi’s 90th birthday—the convened at the Sullivan Conference Center at the (JABSOM). Topics of scientific sessions, which ran throughout the day, included in vitro fertilization (IVF), genetics and genome editing.

Yanagimachi founded the UH ����ԴDz� , part of JABSOM, in 2000. Long before that, he had toiled in laboratories devising the reproductive science that led to assisted fertilization in vitro.

I have always been curious about nature, about the wonder of life, since I was a boy.
—Ryuzo Yanagimachi

In the early 1960’s, as a post-doctoral fellow in the laboratory of the world-renowned M.C. Chang of the Worcester Foundation of Experimental Biology, Massachusetts, Yanagimachi put rodent eggs and sperm in a petri dish under the lenses of a microscope and watched the sperm enter into the egg. It was the first time that had been done with rodents.

This IVF was the beginning of his and other scientists’ analytical studies of fertilization in mammals, eventually including humans.

What inspired him then? “I have always been curious about nature, about the wonder of life, since I was a boy,” Yanagimachi said recently.

For more on this story, see the .

—By Tina Shelton

The proprietary Cardax astaxanthin compound CDX-085 developed by the University of �鶹��ý at ����ԴDz� (JABSOM) and �鶹��ý based life sciences company . was selected by the for its anti-aging Interventions Testing Program. The institute is part of the National Institutes of Health (NIH).

“Getting into the Interventions Testing Program with the National Institute on Aging is a game-changer,” said Bradley Willcox, professor and director of research at JABSOM’s . “It puts CDX-085, Cardax’s proprietary astaxanthin compound, into a very elite club of compounds that have the potential to become true anti-aging therapies.” Willcox is principal investigator of the NIH-funded Kuakini �鶹��ý LIFESPAN and HEALTHSPAN Studies and Cardax Scientific Advisory Board member.

In March of this year, JABSOM and Cardax jointly announced that CDX-085 showed the ability to significantly activate the FOXO3 gene in mice, which plays a proven role in longevity.

“Out of all the compounds they could have chosen, they chose ours,” said David G. Watumull, Cardax CEO. “It’s an important validation of the work that we’ve done here in �鶹��ý.”

The National Institute on Aging ranked the proposal submitted by Willcox and Richard Allsopp, associate professor at JABSOM’s , a “high priority,” its highest ranking.

“The information we get from the ITP is going to be quite significant and should greatly enhance our knowledge of how astaxanthin/CDX-085 affects aging,” said Allsopp.

The National Institute on Aging funds the rigorous and extensive studies included in the ITP, which are conducted at several labs across the country.

The ITP will build upon the research by JABSOM and Cardax demonstrating the ability of CDX-085 to activate the important anti-aging gene FOXO3 in mice. CDX-085, like the company’s first generation dietary supplement, ZanthoSyn™, delivers astaxanthin to the bloodstream with optimal absorption and purity.

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—By Tina Shelton

Promising anti-aging results have been shown by a study of the compound Astaxanthin by researchers at the University of �鶹��ý in partnership with the life sciences company .

The Astaxanthin compound CDX-085, developed by Cardax, showed the ability to significantly increase the expression of the FOXO3 gene, which plays a proven role in longevity.

“All of us have the FOXO3 gene, which protects against aging in humans,” said Bradley Willcox, professor and director of research at the , JABSOM, and principal investigator of the National Institutes of Health-funded Kuakini �鶹��ý Lifespan and Healthspan Studies. “But about one in three persons carry a version of the FOXO3 gene that is associated with longevity. By activating the FOXO3 gene common in all humans, we can make it act like the ‘longevity’ version. Through this research, we have shown that Astaxanthin ‘activates’ the FOXO3 gene,” said Willcox.

“This preliminary study was the first of its kind to test the potential of Astaxanthin to activate the FOXO3 gene in mammals,” said Richard Allsopp, associate professor, and researcher with the JABSOM .

In the study, mice were fed either normal food or food containing a low or high dose of the Astaxanthin compound CDX-085 provided by Cardax. The animals that were fed the higher amount of the Astaxanthin compound experienced a significant increase in the activation of the FOXO3 gene in their heart tissue.

“We found a nearly 90 percent increase in the activation of the FOXO3 ‘Longevity Gene’ in the mice fed the higher dose of the Astaxanthin compound CDX-085,” said Allsopp.

“This groundbreaking University of �鶹��ý research further supports the critical role of Astaxanthin in health and why the healthcare community is embracing its use,” said David G. Watumull, Cardax CEO. “We look forward to further confirmation in human clinical trials of Astaxanthin’s role in aging.”

“We are extremely proud of our collaborative efforts with Cardax on this very promising research that may help mitigate the effects of aging in humans,” said UH Vice President of Research Vassilis L. Syrmos. “This is a great example of what the �鶹��ý Innovation Initiative is all about—when the private sector and government join forces to build a thriving innovation, research, education and job training enterprise to help diversify the state’s economy.”

Read more about the .

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—By Tina Shelton

Researchers at the at the University of �鶹��ý (JABSOM) hope that patients with hemophilia could one day be treated with gene therapy delivered by tiny bubbles.

The microbubbles are made of lipid molecules that won’t dissolve in water. The bubbles are made with DNA that expresses therapeutic genes, and are then injected into the bloodstream. As the bubbles pass through the liver, a beam of ultrasound pops them, and the DNA is deposited in the liver cells, where it makes the missing clotting factor. Hemophilia is an attractive target for gene replacement therapy because the disease results from a single gene mutation, and low levels of the normal protein can restore clotting function.

“Hemophilia is a chronic debilitating disease. If we can treat it simply, cheaply and noninvasively with gene therapy we will have helped to fulfill the promise of the modern medical era,” said Professor and center Director .

The technique could provide an alternative to current treatments for hemophilia, which require frequent injections of a protein (Factor VIII or Factor IX), which is expensive and inconvenient.

“We were able to improve clotting in mice for months after a single treatment,” said Shohet.

Hemophilia affects about 20,000 men and boys in the United States and perhaps 400,000 worldwide. Most affected individuals have a severe form of the disease and suffer from frequent and spontaneous bleeding episodes that can result in serious complications.

The study was led by JABSOM researchers Cindy Anderson and Chad Walton. Other investigators included JABSOM’s Abigail Avelar and Stefan Moisyadi of the .

The findings were published in the scientific journal .

—By Tina Shelton