Melody Nguyen
Program: Molecular Genetics and Genomics
Current advisor: Jonathan R. Brestoff, MD, PhD, MPH
Undergraduate university: Johns Hopkins University
Research summary
My rotation project focused on uncovering the cellular mechanisms that govern mitochondrial transfer into macrophages, a process that challenges the long-held assumption that mitochondria are strictly inherited through cell division. While mitochondria are best known as energy-producing organelles, recent research reveals a surprising form of intercellular communication: the horizontal transfer of mitochondria between developmentally unrelated cells. One such route involves the ejection of free, intact mitochondria into the extracellular space, where they can be captured by immune cells such as macrophages. Despite increasing recognition of this phenomenon, the mechanisms underlying free mitochondrial uptake remain poorly understood. My project aimed to identify how macrophages internalize these extracellular mitochondria and what molecular signals determine their fate once inside the cell. I used chemical inhibitors to target specific endocytic pathways in macrophages and employed live-cell imaging and flow cytometry to track the binding and internalization of fluorescently labeled mitochondria. Through this approach, I began to dissect the cellular entry routes and early trafficking decisions that govern whether mitochondria are degraded or successfully escape into the host cytoplasm. This work provides a foundation for understanding how macrophages engage with extracellular mitochondria, a process with potential implications for immunity, inflammation, and metabolic disease.
Graduate publications