Proceedings of the National Academy of Sciences of the United States of America

About the PNAS Member Editor
Name Darnell, Robert B.
Location The Rockefeller University
Primary Field Cellular and Molecular Neuroscience
Secondary Field Medical Genetics, Hematology and Oncology
 Election Citation
Darnell unraveled functions of RNA binding proteins first identified as onconeural autoantigens. He established Nova-1 as the first tissue-specific splicing regulator, devised a method for identifying RNA-protein complexes in the brain, and demonstrated that RNA-binding proteins regulate a coherent set of synaptic transcripts that underlie paraneoplastic disorders and autism.
 Research Interests
Dr. Darnell is a physician scientist who has pioneered next-generation approaches to understanding RNA genomics in human disease. He is a world's expert in the study of the paraneoplastic neurologic disorders (PNDs), diseases associated with cancer, tumor immunity and autoimmune brain disease. Much of the lab has focused on translational studies of the PNDs, proposing that they provide a basic approach to understanding brain specific functions co-opted by tumor cells, as well as the best documented example of naturally occurring human tumor immunity amenable to study. The lab's studies of disease mechanism, discovering PND antigen-specific CD8+ T cells in these patients, was foundational to the new field of immuno-oncology. He developed molecular approaches to understanding disease pathogenesis and discovering the presence of neuron-specific systems for RNA regulation in the brain, and developing HITS-CLIP, the gold-standard for studying RNA-protein interactions in vivo. The basic lab combined genetic approaches with biochemistry and new methods development to study RNA regulation in neurons. The lab discovered rules predicting brain-specific alternative splicing, showing the first evidence for biologic coherence of RNA regulation in vivo. This work developed into a general understanding of how genome-wide RNA-binding maps predict protein-RNA regulation, in which the position of binding determines the outcome of RNA regulation, first discovered with Nova and now found to be true for a host of RNA regulatory proteins (Nature 2006, 2008). The lab also developed Ago HITS-CLIP (Nature 2009), a precise means of pinpointing protein-RNA and miRNA-mRNA regulatory sites on a genome-wide basis, and hence a means to understand the interactions regulating RNA expression.

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