Sarah Gregor Maps Ferroptosis Pathways in Inherited Blood Disorders

Sarah Gregor investigates the metabolic responses and ferroptosis pathways involved in blood disorders.

Image credit:St. Jude Children’s Research Hospital, ©iStock.com, Eoneren

Sarah Gregor is a postdoctoral researcher at St. Jude Children’s Research Hospital, where she studies how ferroptosis—an iron-dependent form of regulated cell death—contributes to inherited blood disorders such as beta-thalassemia and sickle cell disease. In this Postdoc Portrait interview, she discusses the significance of her work and the impact she hopes it will have.

Investigating Ferroptosis in Blood Disorder Models

Q | What scientific problem are you working to solve?

As a biochemist, I have long been interested in how cells detect and adapt to changes in their environment. During my graduate training, I studied metabolic pathways that help cells respond to oxidative stress, limited nutrients, and shifting energy demands. I was particularly interested in how enzymes act as metabolic sensors, redirecting nutrients through connected pathways to maintain cellular balance. In my postdoctoral work at St. Jude, I have applied that interest to ferroptosis, a form of regulated cell death driven by iron-dependent lipid damage. My research examines how ferroptosis contributes to beta-thalassemia and sickle cell disease, two inherited disorders in which red blood cells face persistent oxidative and iron-related stress. By identifying the metabolic pathways that encourage or suppress ferroptosis, I hope to explain why some cells are vulnerable while others resist it. This work could also reveal regulators and biomarkers that help prevent cellular damage and improve outcomes for patients.

Q | What drew you to cellular metabolism?

My interest in cellular metabolism grew from recognizing that metabolic pathways form a dynamic network influencing nearly every aspect of cell biology. Rather than simply supplying energy and molecular building blocks, these networks convey information about a cell’s surroundings and help coordinate its response. I was captivated by the fact that few cellular processes operate independently of metabolism. It also became clear that many human diseases involve substantial metabolic changes, creating opportunities to clarify disease mechanisms and develop new treatments. That perspective led me to study the relationship between metabolism and cellular regulation during my doctoral training and, ultimately, to investigate ferroptosis, where metabolism, iron balance, and oxidative damage intersect. Exploring those connections in beta-thalassemia and sickle cell disease continues to motivate my research.

Q | What is one unexpected lesson you have learned from your research?

Metabolism continually surprises me in the laboratory. One of my most important lessons is that diseases with similar clinical profiles do not necessarily respond in the same way at the metabolic level. Our findings show that although beta-thalassemia and sickle cell disease share features of metabolic stress and have comparable implications for red blood cell health, they can rewire their metabolism in markedly different directions. This was unexpected and reinforced the need to understand the distinct biology of each disease rather than assume that similar symptoms arise from identical mechanisms. More broadly, it has deepened my appreciation for how adaptable and context-dependent metabolism can be—and how much remains to be learned about cellular responses to disease-related stress.

Q | If your research succeeds, how could it affect science or society?

A quote from computer scientist Daphne Koller has stayed with me: “We are doing a pretty good job at manufacturing keys, but they are generally for the wrong locks.”

If my work succeeds, I hope to identify the right “lock”—a biomarker that reveals cellular vulnerabilities and helps determine whether targeting ferroptosis could be beneficial. Beta-thalassemia and sickle cell disease are complex, and even patients with similar clinical features may respond to metabolic stress in different ways. Recognizing those differences could support more precise treatment strategies rather than assuming that one therapy will work equally well for everyone. More broadly, I hope this research improves our understanding of how metabolism shapes disease and highlights the importance of finding the right biological target before developing another therapeutic “key.”

Q | What question are you most excited to answer next?

I am especially eager to determine how ferroptosis contributes to beta-thalassemia and sickle cell disease. Although ferroptosis is a relatively recently recognized form of cell death, its role in these blood disorders remains poorly understood. I want to characterize how it manifests in these conditions and how it affects red blood cell health and survival. Because ferroptosis connects iron handling, lipid metabolism, and cellular stress, studying it in these disorders may also reveal previously unrecognized links between metabolic dysfunction and disease progression. Ultimately, I hope to uncover an underappreciated mechanism of cellular damage and determine whether it could point to new ways of understanding and treating these diseases.

Responses were edited for length and clarity.

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