Membraneless organelles, composed of RNA and RNA binding proteins, are an important interface for RNA biology research in neurodegeneration. We use live cell imaging and APEX proximity labeling, proteomics and transcriptomics to characterize membraneless organelles. We are interested in understanding the potential connection between stress granules, one type of membraneless organelles and aberrant phase separation in disease, including discovery of mechanisms for nucleation of insoluble aggregates that are present in patient brain and spinal cords.
We previously showed that microRNA malfunction is mechanistically related to ALS and discovered that RNA-binding proteins, which are mutated in ALS, disrupt the microRNA biogenesis machinery. We also explore the consequent disruption of neuronal pathways, downstream of specific miRNAs. These studies reveal the neuro-pathology involvement of small RNAs and demonstrated the involvement of motor-neuron specific miR-218 in ALS.
Collaborators: Paul Anderson, Pavel Ivanov, Nancy Kedersha (Harvard Medical School); Tamar Geiger (Tel Aviv University); John Ravits, Sam Pfaff (UC San Diego);