Ashlyn Widmer ’27 (left) works in the lab with Assistant Professor of Biology Rebecca Clements.
Twenty-five trillion red blood cells ferry oxygen from the environment to the tissues of your body. Ashlyn Widmer ’27 has spent her summer questioning whether they do something more: What if red blood cells are secretly part of the immune system?
Red blood cells are famously known to have one job — to carry oxygen. As a red blood cell matures, it ejects its own nucleus and nearly all its internal machinery, the tools a cell needs to read genes and build proteins. Stripped down so much, it seems impossible for red blood cells to matter to the immune system. For decades, scientists assumed that they didn’t.
Working in the lab of Assistant Professor of Biology Rebecca Clements, Widmer studies cells that haven’t stripped down yet. Called erythroid progenitors, they’re the young, unfinished version of red blood cells — nucleus intact, machinery still running. Textbooks placed them in bone marrow, but doctors kept finding them somewhere they shouldn’t be: drifting through the blood of sepsis patients, and, strangely, in the blood of fetuses and newborns.
“They found that it can be a marker of mortality,” Widmer says, describing how sepsis patients with high numbers of these cells in their blood often take a turn for the worse. Nobody knew why these young cells were escaping into the bloodstream at all, let alone what they were doing there.
That mystery is what pulled Widmer in. She grows red blood cell precursors from umbilical cord blood, then works through them one gene at a time — seven genes total, each tied to how a cell senses foreign DNA and RNA. She silences one, then watches: Does the cell still react correctly when it meets DNA in the blood? Gene by gene, she’s isolating which ones usually matter.
Around that project sit smaller ones. The cells are unusually fragile, so she’s had to work out how to crack them open without destroying them. She tracks her seven target proteins as the cells mature, watching how they shift. And she observes, tests and studies cells under the microscope, searching for any small detail that might turn out to be important.
Why fetal and newborn cells specifically? Widmer points to pregnancy’s balancing act: A fetus is technically foreign tissue, so a mother’s immune system has to learn restraint, even as the fetus prepares for a world full of germs it’s never met. Whether that transition shapes these cells, whether the effects echo in later conditions including allergies or autoimmune disease, is still an unanswered question.
“We don’t really know," Widmer admits. "That's also kind of what we're trying to figure out."
The uncertainty doesn't bother her; it's what drew her to immunology in the first place. She's weighing graduate school, though she's not committed to a path yet — for now, she's more drawn to the open question itself. "I kind of wanted to just be part of that," she says.
The work is still in progress as Widmer waits to find out whether each gene was actually silenced, but there have been small surprises. Cells she isolated one by one, expecting them to struggle alone, instead have been growing pretty well.
If Widmer's results are confirmed, they could help explain why newborns get sick so easily, and why these same young cells reappear, ominously, in the blood of critically ill adults nearing death. A cell dismissed for decades might end up mattering most at both ends of life.
This article was written by Jackie Chen ’29 as part of the Hoskins Frame Summer Science Writing Scholars program.