Shinji Miyata
Faculty of Agriculture, Tokyo University of Agriculture and Technology
I earned his Ph.D. from Nagoya University in 2006 under the mentorship of Prof. Ken Kitajima, specializing in sialic acid research. I did postdoctoral research at UCSD under direction of Prof. Victor D. Vacquier. In 2007, I initiated glycosaminoglycan research as a postdoctoral researcher under the supervision of Prof. Hiroshi Kitagawa at Kobe Pharmaceutical University. Following this, I served as an Assistant Professor at Nagoya University from 2013 to 2019. In 2019, I established my laboratory at Tokyo University of Agriculture and Technology, focusing on hyaluronan-proteoglycan complexes in the nervous system.
The 14th International Hyaluronan Conference (HA 2023) took place from June 4th to 8th, 2023, at the Hilton Hotel in Portland, Oregon, United States (Photo 1). Portland is a popular city known for its blend of natural beauty and urban vibrancy. It is also referred to as the City of Roses, and the month of June, when the conference took place, coincided with the full bloom of over 10,000 roses grown in the International Rose Test Garden in Washington Park (Photo 2).
The organizers of HA 2023 were Dr. Paul Bollyky (Stanford University) and Dr. Larry Sherman (Oregon Health & Science University) (Photo 3), with Dr. Anthony J. Day (Manchester University), Dr. Timothy Bowen (Cardiff University), Dr. Soma Meran (Cardiff University), and Dr. Melanie Simpson (North Carolina State University) serving on the organizing committee. This international conference is held every 2-3 years under the auspices of the International Society for Hyaluronan Sciences (https://ishas.org/). The previous conference, HA 2021, was held online due to the impact of the pandemic. It was a remarkable conference organized by Dr. Paul Bollyky and Dr. Larry Sherman, recognizing the continuous progress in hyaluronan research even in the midst of the pandemic. However, it was indeed challenging for the author to participate from Japan in the midnight sessions due to the time difference. This year, after a gap of 4 years since HA 2019, the conference was held on-site, and many researchers were delighted to reconnect. HA2023 attracted 142 participants from more than 15 countries and featured 53 oral and 43 poster presentations (Photo 4). The conference is unique in that it brings together a wide range of researchers, from molecular-level basic research to clinical and industrial applications. Unlike larger conferences, the open interaction among researchers is another attraction of this meeting. Additionally, there were representatives from 25 companies, reflecting the high level of industrial interest in hyaluronan research. The titles of each session were as follows:
On the first day, Dr. David Jackson (Oxford University), the recipient of the Rooster Award, gave the keynote lecture (Photo 5). His presentation explained the significant contributions of his research to the understanding of the structure and function of hyaluronan receptors. Particularly surprising was the finding that two homologous receptors, CD44 and LYVE1, interact with hyaluronan in very different ways. Afterwards, a banquet was held on the top floor of the Hilton Hotel with a spectacular view of snow-covered Mt. Hood.
The second day started with a keynote speech by Dr. Paul Kubes (University of Calgary), highlighting the importance of the interaction between CD44 and hyaluronan in the infiltration of myeloid cells into tissues. Since it is not possible to cover all the presentations from the ten sessions, I will only mention the ones that personally left an impression. Session 1 featured presentations on the metabolism and biosynthesis of hyaluronan. Dr. Yu Yamaguchi (Sanford Burnham Institute) presented his thorough investigation of TMEM2, demonstrating that TMEM2 itself is an extracellular hyaluronidase. Although there are conflicting reports, further research is expected to resolve the issue soon. Dr. Matej Simek (Contipro) utilized radiolabeled hyaluronan to show that nearly all orally ingested hyaluronan is metabolized by the gut microbiota. It was surprising to learn that hyaluronan is not absorbed at all in germ-free mice. Research on the effects of orally ingested hyaluronan on the gut microbiota and its impact on the human health is of great importance.
Session 2 continued with presentations focusing on structural biology and biophysical approaches. Dr. Jochen Zimmer (University of Virginia School of Medicine) unveiled the long-sought structure of a hyaluronan synthase, which was reported in Nature in 2022. By integrating structural and biochemical analyses, he proposed a new mechanism for controlling hyaluronan size. Dr. Jochen Zimmer's research group was awarded the ISHAS Renato Iozzo Singular Achievement Award, recognizing their significant contribution to hyaluronan research since the previous conference. Session 3 discussed the importance of hyaluronan in inflammation and immune responses. Dorothea A Erxleben (Virginia Tech and Wake Forest University) received the Mark Lauer Award for the best presentation by a young researcher for her development of a nanopore-based method to analyze the complex of hyaluronan and inter-α-trypsin inhibitor heavy chain, a marker of inflammation.
Following the poster preview, where each presenter had one minute to introduce their posters, Poster Session 1 took place with lively discussions accompanied by wine and beer. Since this was the first time for me to attend the international hyaluronan conference held on-site, I was able to establish friendly relationships with many researchers, including Dr. Larry Sherman. It was also an honor to have a conversation with Dr. Mary K Cowman (New York University) (Photo 6). Her long-standing research on the size of hyaluronan has been a constant source of inspiration for our method of analyzing hyaluronan in the brain. Diana Egorova, a PhD student in my lab, also presented a poster (Photo 7) and was thrilled to have the opportunity to discuss her work with researchers she had known only through their papers.
On the third day, the presentations began with a talk by Dr. Aaron Petrey (University of Utah), the recipient of the 2021 Endre Balazs and Janet Denlinger Award, who discussed the function of TSG-6 and hyaluronan complex in colitis. Sessions 4 and 5 focused on clinical applications, regenerative medicine, and biotechnology. Dr. Nadine Nagy (Stanford University) presented the results of a human clinical trial using 4-methylumbelliferone, a hyaluronan synthesis inhibitor, which showed potential applications in lung diseases, including COVID-19. Dr. Hiroyuki Yoshida (Kao) reported a study in which an N-acetylglucosamine derivative promoted the biosynthesis of epidermal hyaluronan. Other presentations aimed at controlling pathological conditions by regulating hyaluronan synthesis and metabolism. The author recognized that in the near future, regulation of hyaluronan synthesis in human individuals will be important for disease treatment and anti-aging. This was followed by Poster Session 2, where discussions continued as on the previous day.
On the fourth day, the conference started with a keynote lecture by Dr. Jonathan Sleeman (University of Calgary), where we learned about how the size difference of hyaluronan affects biological functions. Session 6 focused on research in the field of neuroscience, and I had the opportunity to present in this session. Receiving valuable feedback from many researchers will greatly contribute to my future research. Dr. Anthony J. Day presented his research on inter-α-trypsin inhibitor heavy chain in age-related macular degeneration. Heavy chain complexed with hyaluronan was discussed in several other presentations, and it will be interesting to see if this unique structure is also involved in other central nervous system diseases. Alec Peters (Oregon Health & Science University) showed interesting data that CEMIP, which is upregulated in inflammatory demyelination, inhibits myelin formation. CEMIP and TMEM2, two highly homologous hyaluronan-degradation-related molecules, will likely attract further attention in the future.
Sessions 7 and 8 reported on hyaluronan research in viral diseases and cancer. Dr. Paul Bollyky reported early on the presence of large amounts of hyaluronan in the respiratory secretions of COVID-19 patients. Understanding the role of hyaluronan in infectious diseases and establishing methods to control it will be crucial for preparedness in the next pandemic. In the evening, a dinner cruise was organized (Photo 8). The ship cruised along the Willamette River for two and a half hours, and participants enjoyed a meal while listening to live music and socializing (Photo 9).
On the final day's Session 9, the importance of hyaluronan in intracellular signaling was discussed. Dr. Harry Karmouty-Quintana (University of Texas Health Science Center) reported that the increase in hyaluronan in chronic lung diseases is regulated by selective polyadenylation of HAS2 mRNA, and it is intriguing to explore whether similar mechanisms occur in other diseases. Dr. Vincent C. Hascall (Cleveland Clinic) showed the mechanism by which heparin inhibits hyaluronan synthesis under high glucose conditions. This research is the high road of biochemical analysis. I was greatly inspired by the fact that a legend in hyaluronan research is still working on his research.
Session 10 focused on studies related to development and aging. Dr. Kathryn L. Schwertfeger (University of Minnesota) showed that fibroblasts synthesize hyaluronan during mammary gland development, and tissue-resident macrophages express LYVE1, resulting in an interaction between the two cell types. The presentation also suggested a connection between abnormal mammary hyaluronan and breast cancer. As the conference came to a close, Dr. Vivien Coulson-Thomas (University of Houston), the recipient of the 2023 Endre Balazs and Janet Denlinger Award, presented on the significance of hyaluronan in the cornea.
As a personal reflection on my first participation in the International Hyaluronan Conference, I was initially surprised by the high representation of female researchers. I believe that more than half of the participants were women, and all eight of the young researchers who received Travel Awards were women. Above all, I was impressed by the fact that this was accepted as the norm, highlighting the significant difference from the situation in Japan. In addition, despite the contributions of multiple Japanese companies as sponsors of the conference, I felt concerned about the low participation of Japanese university researchers. While Japanese researchers have made significant contributions to glycobiology research, including hyaluronan research, it is crucial for us to continue showcasing our presence through international conferences. The rapid depreciation of the yen and the global increase in prices have made dining expenses during international conferences approximately two to three times higher than in Japan, leading to hesitation in participating. Nevertheless, what I keenly felt from attending an international conference held on-site after several years is that scientific progress requires essential exchanges between researchers, which are not easily fostered through online events.
Lastly, I would like to thank the organizing committee for inviting the me to HA 2023. Some of the photos were posted with permission from ISHAS Twitter (https://twitter.com/ISHAS_org). Dr. Anna Plaas (Rush University) announced that the next International Hyaluronan Conference will be held from June 9th to 12th, 2025, in Chicago, Illinois, USA.
