First Grant

I am pleased to report on my participation in the 17th Young Researcher's Forum for Pharma- and Bio-Business 2018, hosted by the Division of Biological Chemistry of the Pharmaceutical Society of Japan. The event was held over two days, Saturday, September 1, and Sunday, September 2, 2018, at the Oe Campus of the Faculty of Pharmacy, Kumamoto University.

This unique forum, established in 2001, features 10-minute oral presentations followed by a generous 10-minute Q&A session. It focuses on nurturing young researchers. In each session, numerous advisors are present in addition to the chairperson, encouraging critiques and questions from the diverse perspectives of professors active in various fields. This setup accelerates in-depth discussions between student presenters and the audience, aiming to improve students' Q&A skills and knowledge, and ultimately advance their research. This year, young researchers from a wide range of positions, from assistant professors to fourth-year undergraduate students, presented their work from biological science laboratories across Japan. Furthermore, for the 52 student presentations, an even greater number of 69 professors, all wishing for the students' growth, provided evaluations.

At this forum, I gave an oral presentation on the first day, September 1. Through a 10-minute discussion with distinguished professors, I received feedback from various angles on the shortcomings and strengths of my research. Researchers from private companies were also in attendance, and I was able to receive valuable opinions from an industry perspective. In addition to having a fulfilling time, I was honored to receive the Best Presentation Award. I am delighted that my research to date has been recognized, and I feel a strong desire to devote myself to the future development of my research.

This valuable experience was made possible by the support of Sato Pharmaceutical Co., Ltd., which encouraged my research. I would like to take this opportunity to express my gratitude.

(Yudai Iino / First-Year Master's Student, Graduate School of Pharmaceutical Sciences)

At the 33rd JSSX/MDO Joint International Meeting, I gave a poster presentation on the analysis of expression level changes of MDR1 and BCRP with the progression of pregnancy, using quantitative targeted proteomics with LC-MS/MS. Many of the attendees were interested in the protein analysis method used in this study, and we had a fruitful exchange of opinions on sample preparation methods and protein analysis using LC-MS/MS.

Among other researchers, an interesting presentation was "Significance of post-transcriptional regulation of drug-metabolizing enzymes: Perspective insight into future pharmacotherapy" by Dr. Miki Nakajima of the Laboratory of Drug Metabolism and Pharmacokinetics at Kanazawa University. In her lecture, she spoke about the protein expression control mechanism of CYP and UGT by non-coding RNA, which her group discovered. It was a new and very interesting finding that the amino acid sequence changes and protein expression levels are altered by RNA editing, where RNA's A becomes I, and RNA methylation, where RNA adenosine is methylated.

Many graduate students from other universities participated in this conference, and I was very inspired to see them actively serving as organizers in student-led symposia and presenting confidently as symposiasts. Although there were many presentations that were difficult to understand due to my lack of knowledge, I will study the topics that interested me further on my own, apply what I have learned and the feedback I received to my research activities, and improve the content of my research.

Finally, I would like to express my sincere gratitude to Sato Pharmaceutical Co., Ltd. for giving me this opportunity.

(Yumi Ueda / Fourth-Year Student, Doctoral Programs, Graduate School of Pharmaceutical Sciences)

I would like to express my sincere gratitude for being selected for the 1st Sato Pharmaceutical Co., Ltd. Research Encouragement Award.

I am currently researching the carcinogenic mechanism of NPM-ALK, which has been identified as a causative gene for anaplastic large cell lymphoma. NPM-ALK is localized in both the cytoplasm and the nucleus, but previous research has mainly focused on analyzing its function in the cytoplasm. To date, I have discovered that NPM-ALK localizes to the nucleolus in an activity-dependent manner, and I aim to elucidate the molecular mechanism of its nucleolar localization and its function within the nucleolus.

This time, I revealed that the nuclear protein NPM is necessary for the nucleolar localization of NPM-ALK. Additionally, I aimed to clarify the function of NPM-ALK in the nucleolus by preparing a nucleolar fraction and identifying its binding molecules. At the 91st Annual Meeting of the Japanese Biochemical Society, I gave both an oral and a poster presentation on these research findings.

By participating in the conference, I was able to exchange opinions with many researchers and learn about findings and experimental techniques related to nucleolus research. With the support I have received, I intend to devote myself even more to my research in the future.

(Shuki Uchihara / Second-Year Student, Ph.D. program, Graduate School of Pharmaceutical Sciences)

At the 77th Annual Meeting of the Japanese Cancer Association, I gave a poster presentation titled "The Tumor Suppressor microRNA-34a Suppresses Organoids Derived from Human Cholangiocarcinoma," reporting on the tumor-suppressive effect of microRNA-34a (miR-34a) in organoids derived from patients with intrahepatic cholangiocarcinoma.

Cholangiocarcinoma, which has been on the rise in recent years, is a typical intractable cancer with an extremely poor prognosis and is said to be difficult to cure. We have successfully established and long-term cultured organoids derived from patients with intrahepatic cholangiocarcinoma. In previous research, using comprehensive DNA analysis of intrahepatic cholangiocarcinoma organoids and normal bile duct organoids, we revealed that the expression of the tumor suppressor gene miR-34a is suppressed in intrahepatic cholangiocarcinoma.

We also showed that this was caused by abnormal methylation of the CpG island of miR-34a. Forced expression of miR-34a in organoids led to a decrease in the expression of its target genes and suppression of organoid proliferation. These results suggested that miR-34a could be an important target gene in intractable cancer. Furthermore, to develop innovative personalized medicine, we created a temperature-responsive polymer encapsulating miR-34a. When organoids were exposed to it at 37°C, the expression of miR-34a's target genes decreased, suggesting the utility of this polymer.

During the poster presentation, I received questions such as (1) "Does the 37°C environment have an adverse effect on miR-34a?" and (2) "How does its effect differ from that of DNA methylation inhibitors like 5-aza?" I answered that (1) it does not affect miR-34a, and the tumor-suppressive effect is properly observed, so it is fine, and (2) that is a subject for future investigation that I would like to confirm. By reporting my research, I was able to gain new knowledge and perspectives, and to view my own research from multiple angles.

I am deeply grateful to Sato Pharmaceutical Co., Ltd. for their support, which enabled me to successfully present at the conference and learn a great deal.

(Aya Kitahara / Second-Year Master's Student, Graduate School of Pharmaceutical Sciences)

I would like to express my sincere gratitude for being selected for the Sato Pharmaceutical Co., Ltd. Research Encouragement Award. The research encouragement fund was used in its entirety to cover the participation costs for the 24th Annual Meeting of the Japanese Society for Pharmacoepidemiology from October 13 to 14, 2018.

I participated in the conference as a poster presenter for my research topic, "A Survey on the Off-Label Use of Antineoplastic Drugs in Pediatric Patients Using a Large-Scale Hospital Information Database." While I found it challenging to explain my research findings clearly to others, I realized that receiving feedback is a great help in advancing my research. By listening to other research presentations, I also felt it was an opportunity to learn about the various potential applications of the "large-scale hospital information database" beyond my own research.

In addition to presenting my own work, I had the valuable experience of attending symposia over the two days on the current state of newly introduced clinical trial methods and the latest clinical trials. The opportunity to interact with researchers from different backgrounds, such as those from pharmaceutical companies and universities, was stimulating, and I learned a great deal, including presentation techniques. I hope to apply the knowledge I gained at this conference to my future endeavors and will strive to do even better.

Finally, I would like to take this opportunity to express my deepest gratitude to everyone at Sato Pharmaceutical Co., Ltd. for their generous support.

(Mayuko Kuroda / Sixth-Year Student, Department of Pharmacy, Faculty of Pharmacy)

I participated in the 2018 International Meeting on the 22nd MDO and 33rd JSSX, held in Kanazawa City, Ishikawa Prefecture, and gave a poster presentation titled "Synthesis and biological evaluation of novel nevirapine analogs designed to avoid metabolic activation." This research focuses on the anti-HIV drug nevirapine, which is thought to exhibit toxicity due to metabolic activation, and aims to create safer drugs that avoid this activation by modifying its structure. This time, I presented on the synthesis of nevirapine analogs and the evaluation of their metabolic activation, revealing that a previously overlooked mechanism may contribute to nevirapine's metabolic activation. During the discussion, there were many questions about the evaluation methods for metabolic activation and the metabolic activation pathways of nevirapine, leading to a fulfilling discussion.

All the symposia were excellent, and I was fortunate to have the opportunity to listen to lectures by renowned academics, including Dr. Omura from Kyushu University and Dr. Halpert from the University of Connecticut. Among them, the lectures by corporate researchers, such as Mr. Obach from Pfizer, were particularly memorable. By learning about their thoughts and experiences from the front lines of drug discovery and the technologies required there, I feel I was able to grasp the broader flow of research. I also encountered many studies and technologies that were new to me, which made me realize I need to study much more.

Finally, I am very honored to have been selected for the Sato Pharmaceutical Research Encouragement Award. I would like to express my sincere gratitude to Sato Pharmaceutical Co., Ltd. for supporting my participation in this conference and providing me with such a valuable opportunity.

(Yasuhiro Tateishi / First-Year Student, Ph.D. program, Graduate School of Pharmaceutical Sciences)

At the Symposium on the Chemistry of Natural Products, I gave a poster presentation titled "Development of Regioselective Transformation Methods by Enzymatic and Chemical Approaches Useful for Natural Product Synthesis." The content mainly covered new methods for the efficient hydrolysis of polyphenol glycosides, including partial hydrolysis of disaccharide glycosides; regioselective deacylation and acylation catalyzed by lipase using compounds with multiple ester or hydroxy groups in the molecule as substrates; and acyl migration of acylpolyphenols under basic conditions.

I discussed these topics with researchers from university faculties of medicine, pharmacy, science, engineering, and agriculture, as well as from pharmaceutical and chemical companies. I demonstrated the utility of the reactions developed in our laboratory to the conference attendees and provided them with useful information. On the other hand, through discussions with other researchers, I deepened my understanding of my own presentation, clarifying points for improvement and future challenges. I also gained new ideas and insights by listening to presentations from other laboratories. I learned a great deal, especially from the design of efficient synthetic routes and detailed condition studies in total synthesis research of natural products, making it an invaluable experience.

Among the many presentations at the Symposium on the Chemistry of Natural Products, this one was particularly application-oriented. Therefore, in addition to its academic contribution, it has potential for industrial application. For this reason, I believe it will greatly contribute to the development of the applied field of pharmaceutical sciences.

These results were made possible by the Sato Pharmaceutical Research Encouragement Fund, and I would like to express my gratitude here.

(Riichi Hashimoto / First-Year Master's Student, Graduate School of Pharmaceutical Sciences)

I participated in the 24th Annual Meeting of the Japanese Society for Pharmacoepidemiology, held at Tohoku University's Seiryo Hall from October 13 to 14, 2018. The main theme of the meeting was "New Methodologies in Pharmacoepidemiological Research," and there were 32 general presentations (13 oral, 19 poster), one invited lecture, and six symposia, all of which sparked lively discussions.

I gave an oral presentation on "A Study of an Algorithm to Identify Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) from Electronic Health Record Data." SJS/TEN are severe and rare adverse drug reactions that cause damage to the skin and mucous membranes. In recent years, attempts have been made to use medical information databases (DBs) to detect such low-frequency side effects. However, since SJS/TEN are also easily misdiagnosed, bias can arise in the results of epidemiological studies using medical information DBs. Currently, there are no studies in Japan that have explored an algorithm to validly identify SJS/TEN from medical information DBs. Therefore, in this study, we worked on developing such an algorithm in collaboration with the Department of Dermatology, Keio University School of Medicine.

I was greatly honored that my research was highly evaluated by experts at the meeting, and I received an encouragement award. Spurred on by this award, I intend to devote myself even more to my research activities to produce results that will contribute to the advancement of pharmacoepidemiology.

Finally, I would like to express my heartfelt gratitude to Sato Pharmaceutical Co., Ltd. for subsidizing my expenses to attend the conference.

(Toshiki Fukasawa / Second-Year Master's Student, Graduate School of Pharmaceutical Sciences)

On Saturday, September 30, 2018, at the Annual Meeting of the Japanese Cancer Association, I gave a poster presentation titled "Investigation of a Novel Antitumor Mechanism of Epigenetic Therapy in Cholangiocarcinoma and Pancreatic Cancer Organoids."

This was my first opportunity to present at a conference, and it allowed me to introduce my research to researchers from a wide range of fields. Not only that, but by receiving objective opinions from them, the need to confirm pathway dependency through methods like knockdown and to examine the epigenomic state in more detail became clear, providing a guide for my future research. In addition to presenting my own research, I was also able to see and hear presentations from other researchers. By participating in the conference, I was able to acquire a broad range of knowledge that I want to apply in the future.

Furthermore, the Annual Meeting of the Japanese Cancer Association, which I attended, requires all presentation materials to be in English as part of its internationalization efforts. It was a good opportunity to learn about the difficulty of creating a poster in English and the unique English expressions used in research.

For my participation in the Annual Meeting of the Japanese Cancer Association, I received a research encouragement fund from Sato Pharmaceutical Co., Ltd. I would like to express my sincere gratitude here. I will use the experience gained from attending the conference to work even harder on my research.

(Tomoko Yamaguchi / First-Year Master's Student, Graduate School of Pharmaceutical Sciences)