Some research questions can be answered in a few days. Others require a little more patience.
This project definitely belonged to the second category.
Our study, “Neuromedin U ‘innervation’ reprograms myeloid immunosuppression in neuroendocrine prostate cancer,” started with a simple observation: something in the immune environment of prostate cancer was changing early during tumor development, and we wanted to understand why.
The first clue came from studying prostate cancer in mice at different stages of disease. We noticed that neutrophils—immune cells that normally protect us from infection—were accumulating surprisingly early, while the tumor was still developing. At the same time, there were fewer anti-tumor T cells.
That immediately raised a question: what was attracting these neutrophils so early?
When we looked at the genes changing at this stage, one molecule stood out: Neuromedin U (NMU). NMU is a neuropeptide, a small signaling molecule traditionally associated with communication between the nervous system and other tissues. It was not an obvious candidate in prostate cancer, which made it even more interesting.
And this is probably the part of the story that best explains why I stayed with the project.
Sometimes curiosity is a better guide than a timeline
The project turned out to be much slower than most experiments I had worked on. Our mouse model develops prostate cancer over many months, so some key experiments required waiting 40 weeks or more before we could know whether our hypothesis was correct.
That is a long time to wait for an answer.
In practical terms, an experiment could be designed, mice enrolled, samples collected and analyzed—and only almost one year later would we discover whether the idea worked.
During those years, I was occasionally encouraged to put the project aside and focus on something that might move faster. That was not unreasonable advice. Five years is a long time for a project to take shape.
But I found the biology difficult to ignore.
The more we investigated NMU, the more interesting the connection became. We found that NMU could directly attract neutrophils and change their behavior, making them more capable of suppressing T cells. The tumor appeared to be using a signaling molecule to influence the immune system and create an environment less hostile to cancer.
The project also benefited from collaboration, bringing in complementary expertise and generating crucial results that helped move the story forward.
The next question was much harder: did this actually matter for tumor growth?
This was where the 40-week experiments became important.
We found that interfering with the NMU pathway could reduce tumor growth and reshape the immune environment, with fewer suppressive neutrophils and more anti-tumor T cells. Even more interestingly, targeting this pathway could make tumors more responsive to immune checkpoint therapy.
From one molecule to a bigger question
That was the point where the original observation became a much bigger story. What I find most exciting about this work is not simply that we identified NMU as a potential therapeutic target. It is the broader concept behind it.
My research interest has increasingly focused on the communication between the nervous system, the immune system and cancer.
Cancer is often studied as an isolated population of abnormal cells. But tumors are ecosystems. They communicate with immune cells, blood vessels, stromal cells and, increasingly, with the nervous system.
Neuropeptides and neurohormones are particularly interesting because they are essentially messages. They allow one type of cell or tissue to influence another. In this case, our findings suggest that NMU can act as one of those messages, helping shape the immune environment around a tumor.
This opens up many questions that we still do not know the answers to.
Which cells produce NMU at different stages of prostate cancer? Why does its expression increase as tumors become more aggressive? Does NMU affect cells beyond neutrophils? Can blocking NMU be used therapeutically? And are similar mechanisms operating in other cancers?
Those are exactly the kinds of questions I would like to continue pursuing.
The value of not knowing the answer
There is also a personal reason this project has stayed with me.
For me, the most enjoyable part of research is curiosity. Not necessarily knowing where an experiment will end, but seeing something unexpected and thinking: Why is that happening?
Sometimes that curiosity leads to a quick answer. Sometimes it leads to an experiment that takes almost a year to finish.
The latter can be frustrating, especially when you are trying to build a research program and publish results. But occasionally, slow experiments are the ones that force you to ask better questions.
Looking back, I am glad we did not abandon this project simply because it was taking too long.
The work has given us a model in which a neuropeptide can influence the immune landscape of prostate cancer and, importantly, suggests that this communication can be therapeutically manipulated. It also reinforces my interest in understanding how neural signals, immune responses and cancer biology intersect.
In the long term, I would like to build an independent research group focused on this interface—understanding how neurohormones and neuropeptides communicate with tumors and immune cells, and whether these signals can be exploited to develop new treatments.
I also hope to build on the collaborative relationships I have developed throughout my career, including with former colleagues who bring complementary expertise to these questions.
For now, though, I am mostly happy that after several years, many mouse weeks, and quite a lot of waiting, we finally got to tell the story.
And perhaps the main lesson from this project is a simple one: sometimes the interesting question is worth waiting for.