The Bailis Lab studies how the immune system navigates the tension between what its cells are told to do and what their underlying biology can sustain. The immune system is our model of choice for a reason: its cells are constantly activated, forced to grow and transform at extraordinary speed, and sent circulating from the nutrient-rich blood into the harsh, depleted environments of tumors and infected tissues. That makes immune cells a uniquely powerful window onto how biosynthetic capacity and environment shape cell fate, as well as the diseases where that process breaks down.
The Bailis Lab studies how the immune system navigates the tension between what its cells are told to do and what their underlying biology can sustain.
The immune system is our model of choice for a reason: its cells are constantly activated, forced to grow and transform at extraordinary speed, and sent circulating from the nutrient-rich blood into the harsh, depleted environments of tumors and infected tissues. That makes immune cells a uniquely powerful window onto how biosynthetic capacity and environment shape cell fate, as well as the diseases where that process breaks down.
When a T or B cell recognizes a threat, it receives instructions to transform. That one cell must grow, divide many times over, and take on entirely new identity. Some of these cells are programmed to live just long enough to clear an infection, others to remember the threat and provide life-long protection. But receiving the order is not the same as being able to carry it out. A cell must physically rebuild itself into something new, and that act of building has requirements all its own. We’ve found that a cell’s capacity to execute these transitions, set by its core biosynthetic machinery, can determine whether and how completely a program actually runs: not by rewriting the instructions, but by setting whether the cell can meet the demands those instructions impose.
Remarkably, this capacity varies from cell to cell, even among cells receiving the very same signal. We discovered that single-cell differences in metabolism, established within hours of activation and before a cell ever divides, can predict how fast it proliferates, which functions it acquires, and even whether it persists into long-term memory weeks later. Part of a cell’s fate, in other words, is written not only in which genes are switched on (the strategic plan), but in whether the cell has the biosynthetic capacity to see the instruction through (logistics). We are working out the machinery behind this, including how compartmentalized metabolites like mitochondrial NAD serve as the cell’s way of “reading” just how strong a signal really is. We are taking the lessons from this work and applying them to build better adoptive cell therapies to treat cancer, as well as how diet and nutrients influence vaccine and autoimmunity.
Immune cells live in a moving target. The immune system is a liquid organ, and its cells routinely pass from the nutrient-rich bloodstream into tissues where oxygen and nutrients can be scarce: a tumor, a site of infection, an inflamed organ. In that moment, the demands placed on a cell can suddenly outstrip the supply it has to meet them. How a cell manages that gap, between the anabolic load it is carrying and the biosynthetic capacity it can muster, shapes whether it stays resilient and functional or slides toward dysfunction, exhaustion, or death.
We think of this as a cell’s “biosynthetic headroom”: the room it has to absorb new demand before its program begins to fail. Cells with ample headroom buffer stress and hold their state; cells running close to their limit are far more easily pushed into higher-stress, less stable fates. We’ve found that immune cells have a built-in ability to expand this capacity, reprogramming their biosynthetic machinery through stress-adaptation pathways such as the integrated stress response. Modulating this capacity can make T cells markedly more or less durable in hostile environments like tumors. This reframes T cell states like exhaustion not as a fixed genetic fate, but as what happens when demand outruns capacity, and it points toward new ways to make immunotherapies more resilient.
This same logic scales up from the single cell to the whole body. Nearly a billion people live with restricted access to food, and those numbers have been on the rise. Infection in the setting of malnutrition remains a leading cause of death worldwide, particularly in children. Yet we still understand remarkably little about why undernourished people are so vulnerable to infection and respond so poorly to vaccines.
Working with models of chronic malnutrition, we’ve found that even after animals fully recover their weight and immune cell numbers, they remain vulnerable to infection for months, as if the immune system “remembers” the period of scarcity. This suggests that poverty and food access are underappreciated variables in a person’s health history, written into the capacity of their immune system in ways that outlast recovery itself. We are working to define the mechanisms behind this durable reprogramming, with the goal of identifying dietary components and supplements that could help rebuild immune capacity in vulnerable populations. More broadly, we are investigating how key immune cell populations both detect dietary changes and help coordinate the body’s response to them, revealing levers that could be used to tune systemic metabolism and inflammation across diseases.