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Dr Rao’s research has been focused on understanding how signaling pathways control gene expression, using T cells and other cells of the immune system as models. Her laboratory has been particularly interested in a pathway of gene expression that is regulated by calcium influx into many different types of cells: it involves a process known as store-operated calcium entry, which activates a phosphatase, calcineurin, which dephosphorylates and sends a transcription factor, NFAT, to the nucleus. NFAT turns on a large number of genes, in a manner appropriate to the cell type and mode of stimulation; in T cells, it controls both the positive transcriptional programmes of T cell activation and negative programmes known as anergy or exhaustion that attenuate T cell activation. Her laboratory is using RNA interference and CRISPR/Cas9 screens, mice with targeted gene disruption, high-throughput sequencing and other technologies to analyze how genes are regulated and how loss of function of certain proteins leads to diseases such as autoimmunity, immune deficiencies, developmental defects and cancer. A current important focus involves the TET family of 5-methylcytosine oxidases, which control cell lineage specification in many different systems. Profound TET loss-of-function is associated with aggressive cancers, both in human and in mouse model systems, and Dr Rao’s laboratory is examining the mechanisms involved.
Arjana Rao, PhD, Professor and Division Head, Division of Signaling and Gene Expression, La Jolla Institute For Allergy and Immunology