Sezen Meydan, Ph.D.

Cellular surveillance by ribosomes & neuronal translation & translation-related diseases

Research Keywords: ribosome, translation elongation, ribosome stalling, ribosome collisions, disome-mediated signaling, neuronal translation, translation stress

Research Specialty: Ribosome collision biology and translational stress signaling

Research Description: Ribosomes play an essential role in the cell by translating messenger RNAs (mRNAs) into proteins. However, translation is not always a smooth process. Ribosomes can stall due to intrinsic features of mRNAs, limitations in cellular resources, or exposure to environmental stress. When this occurs, trailing ribosomes can collide with stalled ribosomes, forming ribosome collision complexes, also known as disomes.

Cells actively sense these ribosome collisions and use them as molecular signals to initiate stress response pathways that reprogram gene expression and determine cell fate. Thus, ribosomes function not only as protein synthesis machines but also as dynamic sensors of cellular stress.

The Meydan Lab studies the mechanisms of protein synthesis and how perturbations in translation elongation influence cellular physiology and disease. Our research focuses on understanding how ribosome collisions form, how cells detect these events through signaling pathways, and how translational regulation contributes to cellular health. We are particularly interested in how translation is regulated across different cellular contexts, including neurons, and how defects in these processes contribute to human diseases.

Current projects in the lab include:

1. Identifying determinants of ribosome collision formation and signaling during basal and stress conditions
2. The effect of cellular context in the formation and signaling of ribosome collisions
3. The role of ribosome collisions in disease-associated translational stress
4. Consequences of mitochondrial translation inhibition by mitoribosome inhibitors and diseases

We use a combination of biochemical, genomic, and computational approaches. Our laboratory employs sequencing-based methods to study translation genome-wide, including ribosome profiling (Ribo-seq), disome profiling (Disome-seq), and mitoribosome profiling. These approaches are integrated with RNA-seq, molecular biology, and cell biology techniques. Our work utilizes multiple model systems, including Saccharomyces cerevisiae (budding yeast), immortalized human cell lines, and neurons differentiated from induced pluripotent stem cells (iPSCs), allowing us to investigate translation mechanisms across diverse biological contexts. The lab is part of the Vanderbilt Brain Institute and Cancer Cell Biology Program within the Vanderbilt-Ingram Cancer Center.

Significance: Protein synthesis is fundamental to all cellular processes, yet it is highly sensitive to perturbations. Ribosome collisions represent a central point where translational disruptions are detected and converted into signaling events that shape cellular responses. Understanding how ribosome collisions form and how cells use them as signaling platforms will provide insight into mechanisms of gene regulation and may reveal new opportunities for therapeutic intervention in diseases associated with translational stress.

PubMed Link to Dr. Meydan’s Publications