Sarah Gregor is a postdoctoral researcher at St. Jude Children’s Hospital , where she investigates how ferroptosis—an iron-dependent form of cell death—contributes to the pathophysiology of inherited blood disorders, such as beta-thalassemia and sickle cell disease. In this Postdoc Portrait interview, she shares the importance of her work and what she hopes her research will accomplish.
Targeting Ferroptosis in Hematologic Disease Models
Q | What scientific problem are you trying to solve?
As a biochemist, I have long been fascinated by how cells sense and adapt to changes in their environment. Throughout my graduate training, I studied metabolic pathways that allow cells to respond to challenges such as oxidative stress, nutrient limitation, and fluctuations in energy demand. In particular, I was interested in understanding how enzymes can act as metabolic sensors, altering the flow of nutrients through interconnected pathways to help cells maintain homeostasis. During my postdoctoral training at St. Jude Children’s Hospital, I have applied this interest in cellular metabolism to study ferroptosis, an iron-dependent form of regulated cell death driven by the accumulation of lipid damage. My research focuses on understanding how ferroptosis contributes to the pathophysiology of beta-thalassemia and sickle cell disease, two inherited blood disorders in which red blood cells experience chronic oxidative and iron-related stress. By investigating the metabolic pathways that promote or suppress ferroptosis, I hope to better understand why some cells are vulnerable to this process while others are resistant. Ultimately, these studies may reveal new opportunities to prevent cellular damage by identifying potential regulators and biomarkers to improve outcomes for patients with these disorders.
Q | What drew you to studying cellular metabolism?
My fascination with cellular metabolism was ignited by the realization that metabolic pathways are a dynamic orchestra that influence nearly every aspect of cell biology. Rather than serving as simple suppliers of energy and molecular building blocks, metabolic networks actively communicate information about a cell’s environment and help coordinate its response. I was captivated by the idea that virtually no cellular process exists in isolation from metabolism. At the same time, it became increasingly clear that many human diseases are associated with profound metabolic alterations, creating opportunities to better understand disease mechanisms and develop new therapeutic strategies. This perspective drew me toward studying the intersection of metabolism and cellular regulation during my doctoral training and ultimately led me to investigate ferroptosis, where metabolism, iron homeostasis, and oxidative damage converge. The opportunity to explore these connections in blood disorders such as beta-thalassemia and sickle cell disease continues to motivate my research today.
Q | What’s one thing you learned from your research that you didn’t expect?
Metabolism has never failed to surprise while working at the bench and learning to interpret its many facets. One of the most important lessons I have learned is that just because two diseases that appear to have similar profiles do not mean they respond identically at the metabolic level. Our findings have revealed that even though beta-thalassemia and sickle cell disease have similar clinical implications for red blood cell health and share many features of metabolic stress, they can undergo metabolic rewiring in completely different directions. This was unexpected to me and reinforced how important it is to understand the unique biology underlying each disease rather than assuming that similar disease phenotypes arise from the same mechanisms. More broadly, it has made me appreciate how adaptable and context-dependent metabolism can be, and how much we still have to learn about the ways cells respond to disease-associated stress.
Q | If your research succeeds, what could it change for science or society?
There’s a quote by computer scientist Daphne Koller that resonated with me: “We are doing a pretty good job at manufacturing keys, but they are generally for the wrong locks.”
If my research succeeds, I aim to identify a lock, or in other words a biomarker, that can inform us about cellular vulnerabilities and could benefit from targeting this pathway. Beta-thalassemia and sickle cell disease are complex disorders, and even when patients share similar clinical features, their cells can respond to metabolic stress in very different ways. Identifying these differences could help us move toward more precise approaches to treatment rather than assuming that one therapeutic strategy will work equally well for every patient. More broadly, I hope this work contributes to a better understanding of how metabolism shapes disease and demonstrates the value of looking for the right biological target before developing the next therapeutic “key.”
Q | What question are you most excited to answer next?
I am most excited to uncover how ferroptosis contributes to beta-thalassemia and sickle cell disease. Ferroptosis is a relatively recently recognized form of cell death, but its role in these blood disorders remains largely unexplored. I am excited by the possibility of characterizing what ferroptosis looks like in the context of these diseases and understanding how this process contributes to the health and survival of erythrocytes. Because ferroptosis sits at the intersection of iron, lipid metabolism, and cellular stress, studying it in these disorders may also reveal unexpected connections between metabolic dysfunction and disease progression. More broadly, I am excited by the prospect of uncovering a previously underappreciated mechanism of cellular damage and determining whether it could provide a new way of thinking about these diseases.
Responses have been edited for length and clarity.
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