From Japan to Harvard: A Journey Dedicated to Science – Groundbreaking Discoveries in Sleep Research
Can you tell us a little about yourself?
I am Mustafa Korkutata, a research fellow at Harvard Medical School's Division of Sleep Medicine and Neurology, where I study sleep and sleep disorders.
Before that, I completed my Ph.D. at the International Institute for Integrative Sleep Medicine (WPI-IIIS) at the University of Tsukuba in Japan’s Tsukuba Science City, which holds a prestigious position in the scientific community, particularly in the field of sleep research. During my doctoral studies, I discovered a new class of sleep-inducing molecules that could be used in the treatment of insomnia.
For the past six years at Harvard, I have been leading a project aimed at developing an alternative treatment for sleep apnea.
How did you start your scientific career?
Like many students in Turkey, I went through a career selection process during my high school years. What excited me the most at that time was always scientists and their work. Attending their conferences and seminars was a great source of inspiration for me. It was during this period that I read about the nearing completion of the Human Genome Project, which steered me toward the field of genetics. When I heard Francis Crick’s words, “We are about to decipher the alphabet of God’s creation,” I felt immense curiosity and excitement.
Due to the limited scientific opportunities in Turkey, I started following scientific journals to bridge my knowledge gap. In particular, TÜBİTAK’s Science and Technology magazine was an important resource for me.
During this process, I realized that science is not just an accumulation of knowledge but also a process of creativity and production. When I reflected on Nicholas Murray Butler’s words, “There are three kinds of people in the modern world: those who produce things, those who watch things being produced, and those who are unaware of what is happening,” I understood that science is not merely something to be learned but something to be created. To be a true scientist means contributing to humanity’s body of knowledge and making discoveries that benefit people.
Moreover, science is not just an individual endeavor; it is a part of humanity’s collective memory. Science transcends time, carrying both individuals and societies forward. For humanity to progress, it is not enough to simply possess knowledge; one must also generate new ideas, develop them, and pass them on to others. That is why I see science not just as a career but as one of the most powerful ways to leave a lasting impact.
Science is like a relay race—each generation inherits the knowledge produced before them, builds upon it, and passes it on to the next. The discoveries of past scientists form the foundation of our work today. By asking new questions, conducting experiments, and making discoveries, we must carry this legacy forward for future generations. This is why science is not an individual achievement but a collective success and one of the most effective ways to shape the future.
How did you shape your academic career?
First and foremost, I decided that I wanted to establish myself in the world of science. Instead of prioritizing money, I pursued knowledge and aimed to contribute to humanity. For this reason, when choosing a university, I looked for a place where I could receive the best scientific education.
Despite my interest in genetics, my exam score was not high enough to enroll in that program, so I started studying Physics Engineering at Hacettepe University. I thought I could work on biophysics and genetic physics, but I soon realized that this was not possible at the undergraduate level. As a result, I left the program and transferred to the Molecular Biology and Genetics department in Istanbul.
There, I worked on establishing connections with scientists, attending seminars and conferences, and building a professional network. I had realized that having the right connections was crucial for advancing in the world of science.
What did you gain from your first international experience?
In the third year of my undergraduate studies, I used all my financial savings to participate in a summer internship in the United States. This experience provided me with valuable insights into the culture of scientific research. Having the opportunity to directly observe the research environments at prestigious institutions such as Harvard and MIT played a crucial role in helping me understand the differences in scientific thinking across countries.
One of the most striking differences I noticed was how scientific curiosity and a questioning approach were nurtured at the student level. In Turkey, students generally tend to accept the knowledge provided by academic authorities without much questioning. In contrast, students in the U.S. systematically develop the habit of questioning every piece of information. Particularly in classroom settings and academic conferences, I observed how students critically analyzed every data point presented to them, generating new questions—one of the fundamental aspects of scientific thinking.
This experience showed me that the key distinction between those who produce science and those who merely follow it lies in the habit of questioning and critical thinking. In Turkey’s education system, it is common for students to accept the information provided by professors as absolute. However, in the academic environment in the U.S., students engage in the process actively by identifying gaps in knowledge, conducting in-depth analyses, and developing alternative hypotheses instead of passively receiving information.
Through this experience, I realized that one of the most important ways to enhance scientific productivity is to create an academic ecosystem that encourages students to ask questions, rewards critical thinking, and nurtures their scientific curiosity.
What impressed you the most during your work at Harvard and MIT?
The research environment at Harvard and MIT was a major eye-opener for me. The biggest difference I noticed was the approach to scientific thinking. In Turkey, students generally tend to accept the information presented in lectures or conferences as it is, whereas in the U.S., students focus on extracting new questions from every presentation.
One particular observation at Harvard’s conferences stood out to me: when I paid attention to how students think, I realized a key difference. In Turkey, students often ask themselves, “Did I understand this information?” In contrast, students in the U.S. ask, “How can we improve this information?” “What is missing?” “How can I derive a new hypothesis from this?”
Another major difference was the confidence in asking questions. In Turkey, students are often hesitant to ask questions for fear of saying something incorrect. However, in the U.S., students operate with the mindset, “Even if my question is wrong, there’s no harm in asking, because I’ll learn something new in the process.” Moreover, the questions didn’t have to be complex or deeply technical—sometimes even the simplest questions sparked significant scientific discussions.
At a Harvard conference, I observed something striking: participants did not attend presentations just to acquire information; instead, they listened with the perspective of “How can I generate a new question from this?” In contrast, many students in Turkey approach presentations with the mindset of “I need to memorize this.”
To advance in science, it is not enough to simply acquire knowledge—one must challenge it and question it. The inquisitive mindset of students in the U.S. makes them more productive and creative in science. I believe that in Turkey, students should be encouraged to question every piece of information, think critically, and never fear asking even the simplest questions.
How did your studies in Japan begin?
I was accepted into a good master’s program at a university in Turkey, but due to bureaucratic reasons—specifically, my language certificate not arriving on time—I was unable to complete my enrollment. At that time, I realized that application deadlines for universities in Europe and the U.S. had also passed, leaving me in a state of great uncertainty.
Just then, a friend studying in Japan reached out to me and shared insights about the country’s science policies. The Japanese government was making significant investments in science and had created special programs to support international students.
While researching, I found an Integrated Ph.D. program in Human Biology at Tsukuba University, which allowed me to pursue both my master’s and Ph.D. simultaneously. Moreover, unlike other countries, Japan did not require a language certificate at the time of enrollment. Their approach was surprising and impressive to me: “Your passion for science and your eagerness to learn are what matter most. Your language certificate is only required for graduation; you can submit it whenever you are ready.” This human-centered perspective deeply impressed me.
Tsukuba University is part of Tsukuba Science City, a true hub of scientific research. Located near Tokyo, it hosts more than 70 research institutes, and its population is predominantly composed of academics and researchers. The Japanese government allocates large budgets for scientific research, providing financial support to both research projects and students.
What were the differences in the academic system in Japan?
The academic system in Japan was entirely built on productivity. For example, while students in Turkey often study at home and prepare for exams independently, in Japan, students spent most of their time in laboratories and libraries. Home was simply a place to sleep and rest.
At first, I struggled to adapt to this system because I occasionally felt socially isolated. However, an Indian Ph.D. student gave me an important piece of advice: “If you want to succeed here, you must keep yourself busy at all times. You should never have idle time.” This was true—if you stayed idle, the feeling of loneliness could overwhelm you. So, I dedicated myself completely to lab work and scientific projects.
Another major difference was that at the master’s and Ph.D. levels, most courses did not have traditional exams. Instead, students were assessed through weekly or semester-long assignments. Attendance was also strictly enforced—if a student missed a class without an excuse more than once, their grade would be directly affected.
Can you tell us about your research in Japan?
In Japan, I focused on studying the mechanisms of sleep regulation and disorders, particularly investigating Adenosine A2A receptors. Research on these receptors has shown that they play a crucial role in sleep regulation.
In the sleep-wake cycle, the adenosine system in the brain and Adenosine A2A receptors have critical functions. These receptors are sensitive to changes in adenosine levels and can significantly influence both the depth and duration of sleep.
Adenosine A2A receptors belong to a group of receptors that play essential roles in various physiological processes, including those in the central nervous system, immune system, and cardiovascular system. Instead of using classic agonists and antagonists, the use of allosteric modulators can help reduce unwanted side effects and regulate receptor activity more selectively.
For this reason, allosteric modulation of Adenosine A2A receptors holds great potential as a new therapeutic strategy for various conditions, including neurological diseases, sleep disorders, and inflammation.
What methods did you use to measure the allosteric modulation of Adenosine A2A receptors?
In our research, we measured cAMP (cyclic adenosine monophosphate) levels to determine the activation of Adenosine A2A receptors. cAMP is a critical molecule in intracellular signaling, and its production increases when Adenosine A2A receptors are stimulated.
To measure the intracellular increase in cAMP levels caused by A2A receptor activation, we used a FRET (Fluorescence Resonance Energy Transfer)-based immunological assay method.
Which cell systems did you use in your experiments?
To understand the allosteric modulation of Adenosine A2A receptors, we used Chinese Hamster Ovary (CHO) cells. These cells were organized into two different groups: one group expressing Adenosine A2A receptors and another not expressing them. This setup allowed us to directly observe changes in cAMP levels in response to Adenosine A2A receptor activation.
What were the results of these measurements?
In our experiments, we observed that allosteric modulators of Adenosine A2A receptors either increased or decreased cAMP levels. For example, A2AR PAM-1 (a positive allosteric modulator) increased cAMP levels only in CHO cells expressing Adenosine A2A receptors, while no such increase was observed in cells without em>Adenosine A2A receptor knockout.
Additionally, we found that A2AR PAM-1 only exhibited activity in the presence of adenosine and had no effect on its own. These findings demonstrated that allosteric modulation is only effective in the presence of the natural ligand.
What were the results of your experiments in mice?
In our studies, we used genetically modified mouse models. Adenosine A2A Receptor (A2AR) knockout (A2AR-KO) mice allowed us to understand the physiological and behavioral effects of the absence of this receptor. We tested our discovered allosteric regulator molecule in both A2AR-KO mice and mice expressing A2A receptors.
In mice expressing A2A receptors, we observed that our allosteric regulator, in combination with endogenous adenosine, increased slow-wave sleep (SWS) and made sleep deeper. This finding confirmed that the sleep-enhancing effect of our allosteric regulator in the central nervous system was entirely dependent on A2A receptors.
What were the biggest challenges you faced during your research in Japan?
The academic system in Japan was quite different from my first international experience in the U.S.. In Japan, the research process was more individualistic. At Harvard, the research environment was more interactive, and everyone could freely share their ideas. However, in Japan, I observed that students and researchers worked more independently and with greater discipline.
Additionally, scientists in Japan spent extremely long hours in the laboratory. Over time, I adapted to the Japanese work culture and made my research more productive by spending most of my time in labs and libraries.
Another major challenge was the language barrier. Although English was the primary academic language, I occasionally encountered Japanese terms and literature in the lab, which was difficult at first. However, overcoming these challenges gave me valuable experience in understanding a new culture and adapting to different research methodologies.
What is the focus of your research at Harvard?
In my research at the Harvard Medical School, Division of Sleep Medicine and Neurology, I focus on studying the connections of Calca/CGRP-expressing neurons in the parabrachial complex of the brainstem, which serves as one of the key relay stations for emergency signals from the body to the central nervous system.
These neurons play a critical role in responding to threatening stimuli such as pain, hypercapnia (carbon dioxide buildup), and nausea. However, the exact mechanisms by which inputs to these neurons are regulated remain largely unknown.
Our study aims to map the brain regions that directly influence these neurons and detail their synaptic connections
What are the most important findings of your research?
The Calca/CGRP-expressing neurons in the parabrachial nucleus (PB) receive strong projections from various brain regions, primarily the amygdala and the bed nucleus of the stria terminalis (BST).
In our studies, we observed that signals related to pain and hypercapnia are processed by these neurons. Excitatory (stimulatory) inputs originate from regions such as the insular cortex, infralimbic cortex, and hypothalamus.
We identified that GABAergic inhibitory inputs come from areas like the central amygdala (CeA), bed nucleus of the stria terminalis, and periaqueductal gray (PAG). Our optogenetic experiments revealed that GABAergic projections from the amygdala directly inhibit Calca/CGRP neurons in the PB.
We hope that these findings will lead to significant advancements in the treatment of sleep apnea, pain management, and respiratory disorders.
Finally, what advice would you give to young people who want to pursue a career in science?
I would advise them never to lose their curiosity for science. Science is not only learned in laboratories—it is everywhere. The most important thing is to develop a habit of questioning. In Turkey, students often go through a memorization-based education system and may not receive enough encouragement to nurture their scientific curiosity. However, for a young scientist, the most valuable trait is keeping their curiosity alive at all times.
One of the key aspects of progressing in science is learning how to effectively manage experiments and keep detailed records. A scientist should be able to look at their notes 60 years later and replicate an experiment exactly as it was conducted. A scientist is not just someone who conducts experiments, but also someone who systematically analyzes and documents them. Many groundbreaking discoveries happen when a small, overlooked detail in an experiment is later noticed. That’s why developing the habit of taking thorough notes improves the efficiency of scientific work and minimizes errors.
For example, one of the most important lessons I learned from my work at Harvard and in Japan was the importance of systematically documenting experimental processes and results. A well-maintained laboratory notebook helps you understand which hypotheses worked and what factors influenced your results. Furthermore, being able to review past experiments, identify mistakes, and generate new questions is one of the fundamental pillars of scientific progress.
For students looking to gain international research experience, I recommend considering alternative countries like Japan. Science is advancing not only in the West but also in the East. What matters most is to continue questioning, producing, and learning—wherever you are. The process of creation and contribution is more important than the final destination. A researcher with limited resources but an active scientific output is far more valuable than one who has access to top facilities but lacks productivity.
Moreover, scientific progress is often a team effort. If you are part of an active and collaborative research team, that experience is invaluable for your career and scientific growth—regardless of where you are.
To succeed in science, you must keep your mind engaged with your interests, nurture it through creativity, and continuously develop yourself. It is also important to distance yourself from negative people, environments, and thoughts that may hinder your progress. A scientist is not just a consumer of knowledge, but someone who questions, produces, and shares it.
Thank you for this wonderful interview and for taking the time to speak with me.
I hope this conversation provides valuable insights and inspiration to your readers. I truly appreciate the opportunity to be featured on your blog. Thank you again!
References:
1. Korkutata, M., Agrawal, L., & Lazarus, M. (2022). Allosteric modulation of adenosine A2A receptors as a new therapeutic avenue. International Journal of Molecular Sciences, 23(4), 2101.
2. Korkutata, M., De Luca, R., Fitzgerald, B., Khanday, M. A., Arrigoni, E., & Scammell, T. E. (2025). Afferent Projections to the Calca/CGRP‐Expressing Parabrachial Neurons in Mice. Journal of Comparative Neurology, 533(1), e70018.