We asked the two students who were selected for the 2024 Integrated Research Project about various aspects of the project. Please take a look!
【Researcher Name】Sawamura Jun (Graduate School of Pharmaceutical Sciences Department of Medicinal Sciences)
Tan Bryan Cassidy (Graduate School of Medical Sciences Department of Medicine)
【Integrated Research Title】Development and in vivo characterization of a novel blood-brain barrier (BBB) penetrating lysophosphatidylcholine (LPC)-conjugated serotonin compound
【Abstract】
The blood-brain barrier (BBB) strictly controls the movement of chemicals between the bloodstream and brain tissue, often hindering drug development for the central nervous system. To overcome this challenge, researchers continue to explore various strategies for delivering drugs across the BBB. In this research project, we focused on the lipid transporter MFSD2A.
MFSD2A is a transporter localized at the BBB that facilitates the transport of a phospholipid called LPC (lysophosphatidylcholine) from the bloodstream to the brain, supplying essential lipid nutrients to the central nervous system. We hypothesized that conjugating non-BBB-permeable compounds to LPC could enable their delivery to the central nervous system, leading us to initiate this project.
Q1. What prompted you to start this joint research?
It was Mr. Tan’s suggestion on Slack to explore research on Drug-LPC conjugates that sparked this idea. Initially, we were considering using the anticancer drug cisplatin as the payload, but the compound to be synthesized was too specialized. Therefore, for this research, we decided to use the neurotransmitter serotonin as the payload molecule.
Q2. How did you feel about being selected for the Integrated Research Project?
(Sawamura) I felt a strong sense of responsibility to approach it with dedication.
(Tan) I felt extremely honored and decided to do my best to bring this joint project to fruition.
Q3. What is the current progress of your joint research?
The synthesis of the initial target compound has been completed. Additionally, a slightly modified metabolically stable compound is also prepared. Currently we are preparing cells for in vitro experiments to evaluate the compound’s transportation activity.
Q4. What new “insights” have you gained while conducting joint research?
(Sawamura) It is often said that synthesis of compounds is the rate-limiting step in drug discovery research, and I
was able to experience that firsthand in this study.
(Tan) Selecting and designing a drug conjugate with the right “linker” is important to make sure that our drug-of-interest gets cleaved after entering the BBB. I got to experience this firsthand while discussing and planning the compound synthesis with Mr. Sawamura.
Q5. What are some of the difficulties of joint research that you did not think of when you wereplanning (applying for) this project?
(Sawamura) We can’t precisely tell whether a synthesis of new compounds is possible or not unless we try. However we can’t do anything if we prioritize certainty too much. Therefore, I felt it is challenging but important to set the appropriate boundaries of what I can accomplish on my own.
(Tan) It was difficult to predict whether we can actually be able to synthesize the chemical structure that we wanted. Moreover, it was difficult to estimate the synthesis efficiency as well as the purity and quantity of the final compound.
Q6. What is the reaction of your academic advisors and the members around you in the lab?
(Sawamura) I regularly report on this topic during progress meetings within the lab, and during these times, I receive feedback from the staff and professors regarding the design of the compounds and their behavior in the body.
(Tan) I have discussed this extensively with my supervisors in the lab, they were very interested in this potentially novel method of drug delivery across the BBB, as it could lead to anti-cancer drugs being conjugated to the LPC backbone in the future.
Q7. How do you actually conduct this joint research?
Mr. Sawamura conducts synthetic experiments in the laboratory of Professor Ohshima, and cell-based experiment is to be done by Mr. Tan in both Professor Nakamura’s lab and Professor Ohshima’s lab. Progress updates on the synthesis and necessary information exchange are carried out via Slack.
Q8. How did you spend your research budget of 500,000 yen? What could you do/what would you like to do if you had another 500,000 yen?
We are currently using the budget for purchasing the reagent and solvent for synthesis. We want to explore more detailed structure-activity relationship and conduct pharmacokinetic study of the compound if we have another 500,000 yen.
Q9. Do you think there is a good chance of presenting this joint research at a conference or writing a paper? What percentage do you think there is?
It depends on the result of the activity evaluation of the compound, and we expect it is 80%.
Q10. What are your future prospects and aspirations for this joint research?
Even today, drug delivery across the blood-brain barrier remains a significant challenge in drug discovery. We hope this research will serve as a new approach to drug delivery to the central nervous system and be of some use in the future work. Additionally, we also hope that this research is applicable to other kind of payload molecules such as anti-tumor drug cisplatin.
Q11. What are your dreams for the future and what kind of person do you both aspire to be?
(Sawamura) I am about to begin a job at company that develops reagents for scientific research. I aspire to become a highly-trained synthetic chemist that can contribute to the creation of new products that benefit people.
(Tan) I aim to work in an academic lab as a postdoc after I graduate, and eventually aspire to become a professor in the field of biomedical research in the future.
Q12. Please leave a message for the program students who follow to take on the challenge of the Integrated Research Project and joint research.
(Sawamura) This could be a great opportunity to explore a research area that you haven’t encountered before. I think it would be worthwhile to take on the challenge while balancing with your own doctoral dissertation research.
(Tan) I think that this is a good opportunity to gain experience in other research fields which will add to your knowledge and skillset as a researcher. It enables one to “think outside the box” and approach solving problems from different angles which will lead to novel discoveries.
【Added on February 10, 2025】
Click here to see the report of their research results
