Rao Lab

Rao Lab

"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. // Professor, Division of Signaling and Gene Expression
Pfizer Endowed Chair in Cancer Immunology and Oncology

Overview

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: 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. We are 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 we are examining the mechanisms involved.

From The Lab

Dec 9, 2015

TET proteins help maintain genome integrity

Feb 12, 2015

The company you keep

Jul 1, 2013 // San Diego Union Tribune

Vitamin C may help IVF, stem cell quality, fight cancers

Jun 23, 2013 // San Diego Union Tribune

T cell trigger found

Rao Lab

Publications

Genome Biol

A probabilistic generative model for quantification of DNA mudifications enables analysis of demethylation pathways

2016-03
J Exp Med

Control of Foxp3 stability through modulation of TET activity

2016-03
J Immunol

Cutting edge: NFAT transcription factors promote the generation of follicular helper T cells in response to acute viral infection

2016-03
Martinez GJ, Hu JK, Pereira RM, Crampton JS, Togher S, Bild N, Crotty S, Rao A
Current Opinion in Cell Biology

DNA methylation and hydroxymethylation in hematologic differentiation and transformation

2015-12
Ko M, An J, Rao A
Proceedings of the National Academy of Sciences of the United States of America

TMEM110 regulates the maintenance and remodeling of mammalian ER-plasma membrane junctions competent for STIM-ORAI signaling

2015-12
Quintana A, Rajanikanth V, Farber-Katz S, Gudlur A, Zhang C, Jing J, Zhou Y, Rao A, Hogan PG
Nature Communications

Acute loss of TET function results in aggressive myeloid cancer in mice

2015-11
An J, González-Avalos E, Chawla A, Jeong M, López-Moyado IF, Li W, Goodell MA, Chavez L, Ko M, Rao A
Proceedings of the National Academy of Sciences of the United States of America

Simultaneous deletion of the methylcytosine oxidases Tet1 and Tet3 increases transcriptome variability in early embryogenesis

2015-08
Kang J, Lienhard M, Pastor WA, Chawla A, Novotny M, Tsagaratou A, Lasken RS, Thompson EC, Surani MA, Koralov SB,…
Nature Communications

Cancer-associated ASXL1 mutations may act as gain-of-function mutations of the ASXL1-BAP1 complex

2015-06
Balasubramani A, Larjo A, Bassein JA, Chang X, Hastie RB, Rogher SM, Lähdesmäki H, Rao A
Nature Cell Biology

The histone deacetylase SIRT9 controls embryonic stem cell fate via TET-mediated production of 5-hydroxymethylcytosine

2015-05
Etchegaray JP, Chavez L, Huang Y, Ross KN, Choi J, Martinez-Pastor B, Walsh RM, Sommer CA, Lienhard M, Gladden A, Kugel…
Proceedings of the National Academy of Sciences of the United States of America

RNA-binding protein hnRNPLL regulates mRNA splicing and stability during B-cell to plasma-cell differentiation

2015-04
Chang X, Li B, Rao A
Biochemical and Biophysical Research Communications

Store-operated calcium entry: mechanisms and modulation

2015-04
Hogan PG, Rao A
Molecular and Cellular Biology

A zerbrafish model of myelodysplastic syndrome Produced through tet2 genome editing

2015-03
Gjini E, Mansour MR, Sander JD, Moritz N, Nguyen AT, Kesarsing M, Gans E, He S, Chen S, Ko M, Kuang YY, Yang S, Zhou Y,…
Immunological Reviews

TET proteins and 5-methylcytosine oxidation in hematological cancers

2015-01
Ko M, An J, Pastor WA, Koralov SB, Rajewsky K, Rao A
Proceedings of the National Academy of Sciences of the United States of America

Simultaneous sequencing of oxidized methylcytosines produced by TET/JBP dioxygenases in coprinopsis cinerea

2014-12
Chavez L, Huang Y, Luong K, Agarwal S, Iyer LM, Pastor WA, Hench VK, Frazier-Bowers SA, Korol E, Liu S, Tahiliani M,…
Trends in Genetics

Connections between TET proteins and aberrant DNA modification in cancer

2014-10
Huang Y, Rao A
Immunity

In vivo RNA interference screens identify regulators of antiviral CD4(+) and CD8(+) T cell differentiation

2014-08
Chen R, Bélanger S, Frederick MA, Li B, Johnston RJ, Xiao N, Liu YC, Sharma S, Peters B, Rao A, Crotty S, Pipkin ME
Nature Communications

Jarid2 is induced by TCR signalling and controls iNKT cell maturation

2014-08
Pereira RM, Matrinez GJ, Engel I, Cruz-Guilloty F, Barboza BA, Tsagaratou A, Lio CW, Berg LJ, Lee Y, Kronenberg M,…
Nature Immunology

Epigenomic analysis of primart human T cells reveals enhancers associated with TH2 memory cell differentiation and asthma susceptibility

2014-08
Seumois G, Chavez L, Gerasimova A, Leinhard M, Omran N, Kalinke L, Vedanayagam M, Ganesan AP, Chawla A, Djukanovic R,…
Proceedings of the National Academy of Sciences of the United States of America

Dissecting the dynamic changes of 5-hydroxymethylcytosine in T-cell development and differentiation

2014-08
Tsagaratou A, Aijo T, Lio CW, Yue X, Huang Y, Jacobsen SE, Lahdesmaki H, Rao A
Journal of Immunology

Halofuginone-induced amino acid starvation regulates stat3-dependent th17 effector function and reduces established autoimmune inflammation

2014-03
Carlson TJ, Pellerin A, Djuretic IM, Trivigno C, Koralov SB, Rao A, Sundrud MS
Proceedings of the National Academy of Sciences of the United States of America

Lineage-specific expansions of TET/JBP genes and a new class of DNA transposons shape fungal genomic and epigenetic landscapes

2014-02
Iyer LM, Zhang D, de Souza RF, Pukkila PJ, Rao A, Aravind L
Proceedings of the National Academy of Sciences of the United States of America

Distinct roles of the methylcytosine oxidases Tet1 and Tet2 in mouse embryonic stem cells

2014-01
Huang Y, Chavez L, Chang X, Wang X, Pastor WA, Kang J, Zepeda-Martinez JA, Pape UJ, Jacobsen SE, Peters B, Rao A
Nature Genetics

Large conserved domains of low DNA methylation maintained by Dnmt3a

2014-01
Jeong M, Sun D, Luo M, Huang Y, Challen GA, Rodriguez B, Zhang X, Chavez L, Wang H, Hannah R, Kim SB, Yang L, Ko M,…
Proceedings of the National Academy of Sciences of the United States of America

ORAI1 calcium channel orchestrates skin homeostasis

2013-12
Vandenberghe M, Raphaël M. Lehen'ki V, Gordienko D, Hastie R, Oddos T, Rao A, Hogan PG, Skyrma R, Prevarskaya N
Proceedings of the National Academy of Sciences of the United States of America

MicroRNA-directed program of cytotoxic CD8+ T-cell differentiation

2013-11
Trifari S, Pipkin ME, Bandukwala HS, Äijö T, Bassien J, Chen R, Martinez GJ, Rao A
Journal of Immunology

T cell-derived IL-17 mediates epithelial changes in the airway and drives pulmonary neutrophilia

2013-09
Fogli LK, Sundrud MS, Goel S, Bajwa S, Jensen K, Derudder E, Sun A, Coffre M, Uyttenhove C, Van Snick J,…
Nature

Vitamin C induces tet-dependent DNA demethylation and a blastocyst-like state in ES cells

2013-08
Blaschke K, Ebata KT, Karimi MM, Zepeda-Martinez JA, Goyal P, Mahapatra S, Tam A, Laird DJ, Hirst M, Rao A, Lorincz MC,…
Science

Global epigenomic reconfiguration during mammalian brain development

2013-08
Lister R, Mukamel EA, Nery JR, Urich M, Puddifoot CA, Johnson ND, Lucero J, Huang Y, Dwork AJ, Schultz MD, Yu M,…
Nature Structural & Molecular Biology

Initial activation of STIM1, the regulator of store-operated calcium entry

2013-08
Zhou Y, Srinivasan P. Razavi S, Seymour S, Meraner P, Gudiur A. Stathopulos PB, Ikura M, Rao A, Hogan PG
Nature

An siRNA screen for NFAT activation identifies septins as coordinators of store-operated Ca2+ entry

2013-07
Sharma S, Quintana A, Findlay GM, Mettlen M, Baust B, Jain M, Nilsson R, Rao A, Hogan PG
Nature Reveiws Molecular Cell Biology

TETonic shift: biological roles of TET proteins in DNA demethylation and transcription

2013-06
Pastor WA, Aravind L, Rao A
Nature

Modulation of TET2 expression and 5-methylcytosine oxidation by the CXXC domain protein IDAX

2013-05
Ko M, Bandukwala HS, Chavez L, Aijö T, Pastor WA, Segal MF, Li H, Koh KP, Lähdesmäki H, Hogan PG, Aravind L, Rao A
Immunity

Agonist-selected T cell development requires strong T cell receptor signaling and store-operated calcium entry

2013-05
Oh-Hora M, Komatsu N, Pishyareh M, Feske S, Hori S, Taniguchi M, Rao A, Takayanagi H
Current Opinion in Cell Biology

DNA methylation and methylcytosine oxidation in cell fate decisions

2013-04
Koh KP, Rao A
Cell Stem Cell

Stage-specific roles for tet1 and tet2 in DNA demethylation in primordial germ cells

2013-04
Vincent JJ, Huang Y, Chen PY, Feng S, Calvopiña JH, Nee K, Lee SA, Le T, Yoon AJ, Faull K, Fan G, Rao A, Jacobsen SE,…
Nucleic Acids Research

High-resolution nucleosome mapping ot targeted regions using BAC-based enrichment

2013-04
Yigit E, Zhang Q, Xi L, Grilley D, Widom J, Wang JP, Rao A, Pipkin ME
Nature Immunology

Nurr'ishing treg cells: Nr4a transcription factors control Foxp3 expression

2013-03
Bandukwala HS, Rao A
Molecular Cell

O-GlcNAcylation and 5-methylcytosine oxidation: an unexpected association between OGT and TETs

2013-02
Balasubramani A, Rao A
Journal of Experimental Medicine

T cell activation indiuces proteasomal degradation of argonaute and rapid remodeling of the micro RNA repertoire

2013-02
Bronevetsky Y, Villarino AV, Eisley CJ, Barbeau R, Barczak AJ, Heinz GA, Kremmer E, Heissmeyer V, McManus MT, Erle DJ,…
Cell Research

PGC7, H3K9me2 and Tet3: regulators of DNA methylation in zygotes

2013-01
Kang J, Kalantry S, Rao A
Nature Structural & Molecular Biology

New functions for DNA modifications by TET-JBP

2012-11
Huang Y, Rao A
Science

Immunoloty. Cooperative transcription factor complexes in control

2012-11
Martinez GJ, Rao A
Proceedings of the National Academy of Sciences of the United States of America

Heterogeneous nuclear ribonucleoprotein L-like (hnRNPLL) and elongation factor, RNA polymerase II, 2 (ELL2) are regulators of mRNA processing in plasma cells

2012-10
Benson MJ, Aijö T, Chang X, Gagnon J, Pape UJ, Anantharaman V, Aravind L, Pursiheimo JP, Oberdoerffer S, Liu XS,…
Nature Protocols

The anti-CMS technique for genome-wide mapping of 5-hydroxymethylcytosine

2012-10
Huang Y, Pastor WA, Zepeda-Martinez JA, Rao A
Nature Protocols

The GLIB technique for genome-wide mapping of 5-hydroxymethylcytosine

2012-10
Pastor WA, Huang Y, Henderson HR, Agarwai S, Rao A
Proceedings of the National Academy of Sciences of the United States of America

Selective inhibition of CD4+ T-cell cytokine production and autoimmunity by BET protein and c-Myc inhibitors

2012-09
Bandukwala HS, Gagnon J, Togher S, Greenbaum JA, Lamperti ED, Parr NK, Molesworth AM, Smithers N, Lee K, Witherington…
Genes & Development

D-2-hydroxyglutarate produced by mutant IDH1 perturbs collagen maturation and basement membrane function

2012-09
Sasaki M, Knobbe CB, Itsumi M, Elia AJ, Harris IS, Chio II, Calms RA, McCracken S, Wakeham A, Haight J, Ten AY, Snow B,…
Analytical Chemistry

Nontargeted nucleotide analysis based on benzoylhistamine labeling-MALDI-TOF/TOF-MS

2012-04
Wang P, Fisher D, Rao A, Giese RW
Stem Cells

RNA-binding protein L1TD1 interacts with LIN28 via RNA and is required for human embryonic stem cell self-renewal and cancer cell proliferation

2012-03
Närvä E, Rahkonen N, Emani MR, Lund R, Pursiheimo JP, Nästi J, Autio R, Rasool O, Denessiouk K, Lähdesmäki H, Rao…
Nature Chemical Biology

Halofuginone and othe rfebrifugine derivatives inhibit prolyl-tRNA synthetase

2012-02
Keller TL, Zocco D, Sundrud MS, Hendrick M, Edenius M, Yum J, Kim YJ, Lee HK, Cortese JF, Wirth DF, Dignam JD, Rao A,…
Immunity

Interleukin-4 production by follicular helper T cells requires the conserved Il4 enhancer hypersensitivity site V

2012-02
Vijayanand P, Seumois G, Simpson LJ, Abdul-Wajid S, Baumjohann D, Panduro M, Huang X, Interlandi J, Djuretic IM, Brown…
Stem Cells

RNA binding protein L1TD1 interacts with LIN28 via RNA and is required for human embryonic stem cell self-renewal and cancer cell proliferation

2011-12
Narva E, Rahkonen N, Emani MR, Lund R, Pursiheimo JP, Nasti J, Autio R, Rasool O, Denessiouk K, Lahdesmaki H, Rao A,…
Blood

Mutational spectrum analysis of chronic myelomonocytic leukemia includes genes associated with epigenetic regulation: UTX, EZH2 and DNMT3A

2011-10
Jankowska AM, Makishima H, Tiu RV, Szpurka H, Huang Y, Traina F, Visconte V, Sugimoto Y, Prince C, O'Keefe C, His ED,…
Blood

TET2: an epigenetic safeguard for HSC

2011-10
Ko M, Rao A
Proceedings of the National Academy of Sciences of the United States of America

Ten-eleven-translocation 2 (TET2) negatively regulates homeostasis and differentiation of hematopoietic stem cells in mice

2011-08
Ko M, Bandukwala HS, An J, Lamperti ED, Thompson EC, Hastie R, Tsangaratou A, Rajewsky K, Koralov SB, Rao A
Proceedings of the National Academy of Sciences of the United States of America

Dephosphorylation of the nuclear factor of activated T cells (NFAT) transcription factor is regulated by an RNA-protein scaffold complex

2011-07
Sharma S, Findlay GM, Bandukawala HS, Oberdoerffer S, Baust B, Li Z, Schmidt V, Hogan PG, Sacks DB, Rao A
Nature

Genome-wide mapping of 5-hydroxymethylcytosine in embryonic stem cells

2011-05
Pastor WA, Pape UJ, Huang Y, Henderson HR, Lister R, Ko MG, McLoughlin EM, Brudno Y, Mahapatra S, Kapranov P, Tahiliani…
Immunity

Structure of a domain-swapped FOXP3 dimer on DNA and its function in regulatory T cells

2011-04
Bandukwala H, Wu Y, Feuerer M, Chen Y, Koh KP, Ghosh S, Sundrud MS, Stroud JC, Benoist C, Mathis D, Rao A, Chen L
Trends in Cell Biology

Interaction of calcineurin with substrates and targeting proteins

2011-02
Li H, Rao A, Hogan PG
Cell Stem Cell

Tet1 and Tet2 regulate 5-hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells

2011-02
Koh KP, Yabuuchi A, Rao S, Huang Y, Cunniff K, Nardone J, Laiho A, Tahiliani M, Sommer CA, Mostoslavsky G, Lahesmaa R,…
J Immunol

Cutting edge: NFAT transcription factors promote the generation of follicular helper T cells in response to acute viral infection

2016-03
Martinez GJ, Hu JK, Pereira RM, Crampton JS, Togher S, Bild N, Crotty S, Rao A
Cold Spring Harbor Symposia on Quantitative Biology

TET proteins and 5-methylcytosine oxidation in the immune system

2016-08
Tsagaratou A, Rao A
PLoS One

Predicting cell types and genetic variations contributing to disease by combining GWAS and epigenetic data

2016-08
Gerasimova A, Chavez L, Li B, Seumois G, Greenbaum JA, Rao A, Vijayanand P, Peters B
Cell Rep

TET2 regulates mast cell differentiation and proliferation through catalytic and non-catalytic activities

2016-05
Montagner S, Leoni C, Emming S, Della Chiara G, Balestrieri C, Barozzi I, Piccolo V, Togher S, Ko M, Rao A, Natoli G,…

Principal Investigator

rao

Anjana Rao, Ph.D.

Professor, Division of Signaling and Gene Expression

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.

Lab Members

Edahi Gonzales Avalos

Graduate Student

Joyce Chen

Graduate Student

Benjamin Delatte

Postdoctoral Fellow

Romain Georges

Postdoctoral Fellow

Jad Kanbar

Graduate Student

Hyo Kim

Intern

Xiang Li

Postdoctoral Fellow

Matthias Lienhard

Visiting Scientist

Chan-Wang Lio

Postdoctoral Fellow

Isaac Lopez-Moyado

Graduate Student

James Scott-Browne

Postdoctoral Fellow

Vipul Shukla

Postdoctoral Fellow

Susan Togher

Lab manager/ Research Technician III

Sara Trifari

Visiting Scientist

Angeliki Tsangaratou

Instructor

Victor Wong

Postdoc

Lukas Chavez Wurm

Xiaojing Yue

Postdoctoral Fellow

Rao Lab

Research Projects