Research

RNA biology and biomolecular condensates

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. These studies reveal the involvement of small RNAs and particularly motor-neuron specific miR-218, in ALS neuro-pathology.

Biomolecular condensates, AKA, membraneless organelles, which are composed of RNA and RNA binding proteins, are an important interface for RNA biology / neurodegeneration research.

We use live cell imaging, APEX proximity proteomics, transcriptomics and machine learning approaches to characterize biomolecular condensates. We are interested in understanding the potential connection between stress granules and other membraneless organelles and the mechanisms for nucleation of insoluble aggregates that are present in patient brain and spinal cords.

Genetic screens and genomic studies of neurodegeneration

Non- protein coding regions, which encompass 97% of the human genome are overlooked by traditional human genetics association studies. As members of Project MinE and the NYGC ALS sequencing consortiums, we focus our efforts on developing computational methods to explore non-protein coding mechanisms, based on whole-genome sequencing data.

We use scalable base editing technologies, paired with single cell RNA sequencing readouts and deep organellar phenotyping to explain the biological consequences of thousands of genetic variants, reported in neurodegeneration. We orthogonally develop high-throughput transcriptomic-based single cell profiling and machine-learning supported microscopic phenotyping. We map the functional relationships of hundreds of neurodegeneration-associated alleles, across the entire neurodegeneration genetic landscape.

Translational research

We develop disease biomarkers by different data sets, including next-generation sequencing of cell-free RNA from patient biofluids.