"The immune system is an ideal model for studying all
sorts of biochemical processes - development, the regulation of gene
expression, alternative splicing and cellular stress responses, to mention only
a few." - Anjana Rao, Ph.D.
A member of the National Academy of Sciences, Dr. Rao
received her undergraduate and master's degrees from Osmania University in
India and her Ph.D. from Harvard University. After many years as a faculty member at the Harvard Medical
School and the Immune Disease Institute in Boston, she joined the La Jolla
Institute in 2010. She has worked
on signaling and gene transcription for many years, is a member of numerous
advisory panels, and has received several major awards.
Our research has been focused on understanding how signalling pathways control gene expression, using T cells and other cells of the immune system as models. There are several aspects to our research. We are particularly interested in a pathway of gene expression that is regulated by calcium influx into many different types of cells, including cells of the immune system, neurons, and cells in heart, muscle, bone and skin: it involves a calcium sensor in the endoplasmic reticulum, STIM, which couples to a calcium channel in the plasma membrane, ORAI. The increased calcium concentration in the cytoplasm 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. We have also used T cells to study how gene expression programmes are modulated by stress pathways and during cell differentiation. Finally, we are investigating how the TET family of 5-methylcytosine hydroxylases affects DNA methylation patterns and gene expression in embryonic and haematopoietic stem cells. TET proteins appear to be essential regulators of ES cell pluripotency, and their dysegulation is frequently associated with cancer.
We are using RNA interference screens, mice with targeted alterations of genes, 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. The hope is that the research will provide information that could lead to new therapies based on altering gene function.
TET2: an epigenetic safeguard for HSC. Blood. 2011
Mutational spectrum analysis of chronic myelomonocytic leukemia includes genes associated with epigenetic regulation: UTX, EZH2 and DNMT3A. Blood. 2011
Ten-eleven-translocation 2 (TET2) negatively regulates homeostasis and differentiation of hematopoietic stem cells in mice. Proc Natl Acad Sci USA. 2011
Dephosphorylation of the nuclear factor of activated T cells (NFAT) transcription factor is regulated by an RNA-protein scaffold complex. Proc Natl Acad Sci USA. 2011
Genome-wide mapping of 5-hydroxymethylcytosine in embryonic stem cells. Nature. 2011
Structure of a domain-swapped FOXP3 dimer on DNA and its function in regulatory T cells. Immunity. 2011
Interaction of calcineurin with substrates and targeting proteins. Trends Cell Biol. 2011
Tet1 and Tet2 regulate 5-hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells. Cell Stem Cell. 2011
Pore architecture of the ORAI1 store-operated calcium channel. Proc Natl Acad Sci USA.
STIM1 gates the store-operated calcium channel ORAI1 in vitro. Nature Structural & Molecular Biology. 2010
RNAi screening: Tips and techniques. Nature Immunol. 2009
Halofuginone inhibits TH17 cell differentiation by activating the amino acid starvation response. Science. 2009
Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science. 2009
Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs.
J Exp Med. 2009
Regulation of CD45 alternative splicing by heterogeneous ribonucleoprotein, hnRNPLL. Science. 2008
Mouse Eri1 interacts with the ribosome and catalyzes 5.8S rRNA processing. Nat Struct Mol Biol. 2008
Dual functions for the endoplasmic reticulum calcium sensors STIM1 and STIM2 in T cell activation and tolerance. Nat Immunol. 2008
Transcription factors T-bet and Runx3 cooperate to activate Ifng and silence Il4 in T helper type 1 cells.. Nature Immunol. 2007
FOXP3 controls T regulatory function through cooperation with NFAT. Cell. 2006
A genome-wide Drosophila RNAi screen identifies DYRK-family kinases as regulators of NFAT. Nature. 2006
A mutation in Orai1 causes immune deficiency by abrogating store-operated Ca2+ entry and CRAC channel function. Nature. 2006
Deletion of a conserved Il4 silencer impairs T helper type 1-mediated immunity. Nature Immunol. 2004
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