Ahmed Mohamed: Listening to the whispers of the immune system 

When we think about our immune system, we often picture it as a strong defense army, ready to fight off infections and keep us healthy. But what if, instead of just watching how it reacts when illness strikes, we could metaphorically listen to the tiny molecular conversations that our immune cells are having every day?

That is what I have been investigating during my PhD while using advanced tools to decode the language of our genes and discover how the immune system changes in health, disease, and even during something as common as breathing polluted air. 

Our genes do not just hold static information; they are constantly turning on and off in patterns that reflect what our cells are doing. By studying these patterns, a field called transcriptomics, we can begin to understand not only how diseases progress, but also how everyday exposures like pollution or exercise shape our immune system. 

A New Lens for the Immune System 

The human immune system is super complex, with countless cell types communicating through intricate networks. Traditional medicine often looks at “end results,” like whether someone develops cancer or gets sick after exposure to pollution. We wanted to look earlier at the molecular signals that might predict those outcomes before they become visible. 

To approach this, we developed “StellarPath”, a new tool that combines different layers of biological data (what we call “multi-omics”) into a unified picture. Think of it like overlaying weather maps, traffic reports and GPS signals to get a more accurate forecast of what is happening in a city. StellarPath works in a similar way through connecting gene activity, pathways with patient similarity networks to comprehend the outcomes in a holistic way. 

Chronic Lymphocytic Leukemia: Finding the Hidden Regulators 

One focus of my research was Chronic Lymphocytic Leukemia (CLL), a blood cancer that progresses very differently depending on its subtype. There are two subtypes; one is associated with bad outcomes and the other with better outcomes. By analyzing transcriptomic patterns of both subtypes and comparing them to healthy patterns, we highlighted potential biomarkers (i.e. molecular signatures) that could help predict how a patient’s disease will evolve. 

Even more exciting, we identified possible mechanistic regulators, genes and pathways that may be driving the disease subtypes. These insights do not just deepen our understanding of CLL, they could one day guide personalized treatment strategies, helping doctors choose the right therapy for the right patient at the right time. 

Breathing Diesel Exhaust: The Hidden Impact on Immunity 

Beyond cancer, we explored how everyday exposures, such as air pollution, especially diesel exhaust, can shape our immune health. Cities worldwide struggle with this invisible threat, but what exactly does it do to our immune system? 

In our studies, we exposed both brain immune cells (Human induced pluripotent stem cell-derived microglia-like cells) and peripheral immune cells (blood immune cells) to diesel exhaust. The results were eye-opening: 

• Brain-like immune cells showed impaired ability to clean up cellular debris, a process called phago-lysosomal function. 

• Blood immune cells reacted with a mixed response, activating both innate and adaptive pathways and central switches for inflammation. 

• Even more fascinating, sex differences emerged where male and female immune systems did not respond in the same way to diesel exhaust exposure. 

These findings suggest that pollution does not just irritate the lungs; it has ripple effects across the entire immune system, with consequences that might differ from person to person. 

Why This Matters 

Why should anyone outside the lab care about these findings?

Because they point toward a future where we can use molecular signatures as early warning systems for health. Instead of waiting for disease to appear, we could detect immune system stress before symptoms show up.

Imagine a world where a simple blood test could tell you how your body is responding to pollution or whether your cancer is likely to progress quickly. The vision is to build a foundation for predictive, personalized and preventative medicine. 

Closing Thoughts 

The immune system is like an orchestra with countless instruments playing together in harmony, sometimes clashing, sometimes synchronizing beautifully. By studying the transcriptional signals “sheet music” of our cells, we are beginning to hear the subtle changes that signal disease, adaptation or resilience. 

My PhD was one step toward tuning in to that music, with the hope that someday, these insights will translate into better health for all of us. 

Ahmed Mohamed works as a doctoral researcher in the Neuro-Innovation PhD programme. He is doing his PhD at the Neuroinflammation research group on air pollution.