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INFORMATION FOR

Richard Flavell, PhD, FRS

Sterling Professor of Immunobiology; Investigator, Howard Hughes Medical Institute

Research Summary

Richard Flavell is co-discoverer of introns in cellular genes: he showed DNA methylation correlates inversely with, and prevents, gene expression. He was the first to develop reverse genetics as a postdoc with Weissmann and in his own lab continued in this field throughout his career; he is a pioneer in the use of this approach in vivo to study function. Dr. Flavell’s laboratory studies the molecular and cellular basis of the immune response. He has been instrumental in discovering the molecular basis of T-cell differentiation from precursor cells into differentiated subsets. This work led to the discovery of GATA3 as a critical regulator of the Th2 response and the first example of such a molecule in Th cell differentiation. He went on to demonstrate the first case of regulation of gene expression in trans, via ”chromosome kissing.” Moreover his laboratory has elucidated the mechanisms of immunoregulation which prevent autoimmunity and overaggressive responses to pathogens. Specifically, Dr. Flavell's laboratory has elucidated the role of TGF-β in the regulation of immune response. This work is of relevance both to the control of autoimmune disease and the evasion of immune response by tumors.

Dr. Flavell’s laboratory has discovered the role of several receptor families in the innate immune response, including the role of several Toll-like receptors and intracellular Nod-like receptor families (NLRs). This has recently led to the elucidation of function of Nod2 in inflammatory bowel diseases and Nlrp proteins in the production of IL-1. Most recently he has established a fascinating connection between inflammasomes, microbial homeostasis and chronic diseases. He showed that inflammasome dysfunction causes dysbiosis of the microbiota which, in conjunction with a susceptible diet, leads to IBD and Metabolic Syndrome, including Obesity, Fatty Liver disease and Type 2 diabetes.

Speciailzed Terms: Animal Models; Autoimmunity; Diabetes; Gene Expression; Gene Transfer; Genes; Immune System; Lyme Borreliosis Or Lyme Disease; Molecular Cellular Entities; Recombinant DNA; Transgenic Animals; Autoimmunity; Knockout Mice; Lyme Disease; T Cell Lineages; Tolerance; Transgenic Mice

Extensive Research Description

The innate immune system contains genome-encoded receptors that
provide a first line of defense to infection. Activation of innate
immunity triggers adaptive immunity. There are three classes of innate
immune receptors:

  • Toll-like receptors (TLRs), which sense agents in the extracellular/vesicular space;
  • Nod-like receptors (NLRs), which sense microorganisms that penetrate the cytoplasmic space; and
  • RIG-like receptors (RLRs), which recognize viral infection and trigger type 1 interferon production.

We identified the TLRs for double-strand RNA
(TLR3), single-stranded RNA (TLR7), flagellar protein (TLR5), and
lipoprotein (TLR1/2).
Upon penetration of the cytoplasm, NLRs trigger
NF?B activation, interleukin-1 (IL-1) production, or apoptosis. In
humans, NLR mutation correlates with inflammatory disease. Nod2 carries
a leucine-rich repeat region probably recognizing bacterial muramyl
dipeptide, a nucleotide-binding domain mediating conformational change,
thereby enabling oligomerization between CARD domains of Nod2 and
downstream receptor-interacting protein (RIP) kinase, causing
activation of NF?B and antimicrobial peptides. NOD2
is mutated in Crohn's disease (CD), an inflammatory bowel disease
(IBD). Our Nod2-deficient mice were more susceptible to infection with
pathogens delivered to the gut, because of reduced production of
antimicrobial peptides. Thus, patients with CD may be unable to develop
an effective antimicrobial response, causing enhanced infection and
severe inflammation.


The Nalp proteins comprise a second arm
of the NLR family. We study several of these, including Nalp3 (NLRP3),
which senses infection or other stress that leads to K+
efflux and activates the "inflammasome" through oligomerization with
the adaptor apoptosis-associated speck-like protein (ASC), enabling ASC
to bind to and activate caspase-1 to process pro-IL-1ß and other
substrates.

We found that multiple stimuli activate the Nalp3 inflammasome, including Listeria
infection. Jürg Tschopp (University of Lausanne) showed that this
inflammasome recognizes uric acid crystals, explaining the inflammatory
properties of uric acid in gout. We found that alum, a crystalline
immune adjuvant and the only USA-approved human adjuvant, activates the
NALP3 inflammasome, which triggers macrophage inflammatory cytokine
production and adaptive immunity in vivo.

Disruption of the pathway
eliminates alum's adjuvant capacity. Likewise, particulate
environmental pollutants, including silica and asbestos, also activate
the Nalp3 inflammasome to cause devastating chronic inflammatory
disease. Thus, inflammasomes mediate anti-infective immunity,
immunopathology to environmental pollutants, and adaptive immunity.
The immune response sometimes reacts to
self-tissues, causing autoimmunity. How can antigenic stimulation of a
lymphocyte lead to such different outcomes? During an immune response
or in autoimmunity, the lymphocytes divide and differentiate into
effector cells. However, when immune tolerance occurs, the cell is
either inactivated or dies.

How are the decisions made to proliferate,
differentiate, be tolerized, or die, and how is this controlled?


Regulatory cells producing inhibitory cytokines are critical to prevent
autoimmunity. Of these, the CD4+CD25+Foxp3+Treg
is the most studied. The functioning, generation, and maintenance of
regulatory T cells (Treg) are controlled by cytokines. Both
transforming growth factor-ß (TGFß) and IL-10-family cytokines are
important. Mice lacking TGFß develop autoimmunity to several tissues.
To elucidate upon which cells TGFß acts, we expressed a
dominant-negative TGFß receptor (dnTGFßRII) on either T cells or
antigen-presenting cells (APCs). Mice displaying the dnTGFßRII on T
cells recapitulate the diseases of TGFß-knockout mice: autoimmunity and
IBD. In addition to autoimmunity, such animals have an enhanced
anti-infective response, better resistance to infection. Finally, mice
carrying the dnTGFßRII on their T cells are resistant to tumors. Thus,
tumors use TGFß to inhibit the antitumor T cell response; but if TGFß
cannot act, immune clearance of tumors occurs.
To determine whether TGFß controls innate immunity,
we expressed dnTGFßRII using the CD11c promoter, which expresses in
dendritic (DC) and natural killer (NK) cells, both key mediators of
innate immunity. When innate immune cells cannot be inhibited by TGFß,
both NK and DC innate, as well as adaptive, immune responses are
enhanced. CD11c dnTGFßRII mice are also more susceptible to
autoimmunity, because TGFß fails to control APC function. Thus, TGFß
controls T cells, APCs, and NK cells.
We revealed additional mechanisms of TGFß function
by studying conditional-knockout mice lacking TGFßRII on T cells. TGFß
is required for Treg homeostasis and function and TGFßRII must be
present on a target cell for a Treg to be suppressed. We also found
that TGFß controls the magnitude of T helper 1 cell (Th1) response by
setting the level of CD122 ß chain of the IL-15 receptor, which
controls the pool size of Th1 cells. Many cells make TGFß. To determine
which TGFß source is important, we first eliminated TGFß on T cells,
using conditional targeting. Mice with T cells that cannot make TGFß
also developed autoimmune disease and IBD, albeit slower than mice
lacking the receptor on all T cells. Thus, T cell–produced TGFß is
important in immune response, but other sources must play a role.
Regulatory T cells that cannot produce TGFß poorly control IBD, and T
cell–produced TGFß is essential to generate Th17 cells, which mediate
disease in experimental autoimmune encephalomyelitis.
T cells are activated and differentiate into
specialized effector cells.

How is the effector pathway triggered that
is appropriate to the class of infection?
We found the Th2 response is
activated when parasite antigen induces Notch ligand expression on
dendritic cells. This activates Notch in naïve T cells, which in turn
induces GATA3, the key Th2 transcription factor, by a Notch-responsive
promoter. Thus is a pathogenic signal converted to a signal for T cell
differentiation through Notch.

We identified cis-regulatory elements that are the targets of transcription factors, such as GATA3. In the interleukin-4 (IL-4) locus, the IL-4, IL-13, and IL-5 genes are clustered, and several DNA elements within that region are important for gene expression. IL-4 gene regulation occurs through epigenetic mechanisms that target regulatory elements distal from the IL-4
gene. One of these elements is a previously unrecognized locus control
region (LCR) that is found embedded in the introns of the RAD50
gene in the cluster. This LCR, together with these respective promoters
and other cis elements of the locus, is in a preassembled complex in
naïve T cells that serves as a hub from which epigenetic changes in
histone acetylation and DNA methylation occur and enables rapid
response of the loci.

When naïve T cells are activated, both the IL-4 locus on chromosome 11 and the interferon-? (IFN-?)
locus on chromosome 10 are expressed almost immediately, despite the
fact that following differentiation these loci are never coexpressed
but instead are alternatively expressed in the Th2 and Th1 lineages,
respectively. To investigate this rapid coexpression, we examined the
physical relationship between these two loci on the different
chromosomes. The LCR of the IL-4 locus on chromosome 11 and the IFN-?
gene region on chromosome 10 are associated in the interphase nucleus
of the precursor cells but separate upon differentiation into effector
cells. Mutation in the LCR on chromosome 11 delays expression of the IFN-?
gene on chromosome 10. We find other such associations and further
evidence for their functional roles. Thus, regulatory sequences on one
chromosome likely control "in trans" gene expression on other
chromosomes.
Our laboratory retains a long-standing interest in
the underlying mechanisms of apoptosis. The program of cell death is
triggered through the activation of cysteine proteases called caspases.
Caspase-3 and -7 cleave similar substrates. Caspase-7–knockout mice
have only a mild phenotype, but the combination with caspase-3
deficiency results in embryonic lethality. Caspase-3 and -7 are also
required for upstream mitochondrial functions in apoptosis, via a
positive-feedback loop, in addition to their roles as effector
caspases.

  • TGF-b in autoimmune diabetes
  • TGF-b in memory T cell development
  • The role of BCL2 in aging of the immune system
  • AMCase in lung inflammation
  • The role of TGF-b in the immune response to melanoma
  • Generation and analysis of mice with human immune systems
  • Developing immune therapies for Type 1 diabetes
  • Genetic approaches to immune function and tolerance

Coauthors

Research Interests

Biology; Diabetes Mellitus; DNA, Recombinant; Immune System; Immunity; Lyme Disease; Autoimmunity; Gene Expression; Gene Transfer Techniques; Mice, Knockout; Cell Lineage; Lyme Neuroborreliosis

Selected Publications

  • 045 An EGFR ligand maintains scleroderma skin and lung fibrosisOdell I, Steach H, Gauld S, Carr T, Wetter J, Phillips L, Hinchcliff M, Flavell R. 045 An EGFR ligand maintains scleroderma skin and lung fibrosis Journal Of Investigative Dermatology 2022, 142: s8. DOI: 10.1016/j.jid.2022.05.099.
  • 660 Epigenetic regulation of Slamf6 expression in the immune response to melanomaMicevic G, Flavell R, Bosenberg M. 660 Epigenetic regulation of Slamf6 expression in the immune response to melanoma Journal Of Investigative Dermatology 2022, 142: s113. DOI: 10.1016/j.jid.2022.05.1066.
  • Human CD116 fetal liver progenitors migrate to the perinatal lung and give rise to alveolar macrophages in vivoEvren E, Ringqvist E, Doisne J, Thaller A, Sleiers N, Flavell R, Di Santo J, Willinger T. Human CD116 fetal liver progenitors migrate to the perinatal lung and give rise to alveolar macrophages in vivo 2022, 15. DOI: 10.1183/23120541.lsc-2022.15.
  • Reconstruction of Sickle Cell Disease with Circulating Sickling Red Blood Cells in Novel Humanized Cytokines and Liver Mistrg MiceSong Y, Gbyli R, Shan L, Liu W, Gao Y, Patel A, Fu X, Wang X, Xu M, Qin A, Bruscia E, Tebaldi T, Biancon G, Mamillapalli P, Urbonas D, Gonzales D, Krause D, Alderman J, Flavell R, Halene S. Reconstruction of Sickle Cell Disease with Circulating Sickling Red Blood Cells in Novel Humanized Cytokines and Liver Mistrg Mice Blood 2020, 136: 29-30. DOI: 10.1182/blood-2020-141603.
  • Abstract 3441: Transcriptional profiles of CD14+ cells in situ in melanoma reveal plasticity, localization dependent function and specific T cell interactionsMartinek J, Kim K, Lin J, Wu T, Borouchov H, Gulati A, Sun L, Wang V, George J, Henrich P, Marches F, Rongvaux A, Chiorazzi M, Chuang J, Robson P, Flavell R, Banchereau J, Palucka K. Abstract 3441: Transcriptional profiles of CD14+ cells in situ in melanoma reveal plasticity, localization dependent function and specific T cell interactions Cancer Research 2020, 80: 3441-3441. DOI: 10.1158/1538-7445.am2020-3441.
  • Abstract PR12: Paracrine orchestration of intestinal tumorigenesis at the mesenchymal-epithelial interfaceRoulis M, Kaklamanos E, Kollias G, Flavell R. Abstract PR12: Paracrine orchestration of intestinal tumorigenesis at the mesenchymal-epithelial interface Molecular Cancer Research 2020, 18: pr12-pr12. DOI: 10.1158/1557-3125.hippo19-pr12.
  • 186 Immune cell-derived growth factors drive fibrosis in scleroderma and graft-vs-host diseaseOdell I, Flavell R. 186 Immune cell-derived growth factors drive fibrosis in scleroderma and graft-vs-host disease Journal Of Investigative Dermatology 2020, 140: s22. DOI: 10.1016/j.jid.2020.03.190.
  • Bacterial Autoimmune Drug Metabolism Transforms an Immunomodulator into Structurally and Functionally Divergent AntibioticsPark H, Goddard T, Oh J, Patel J, Wei Z, Perez C, Mercado B, Wang R, Wyche T, Piizzi G, Flavell R, Crawford J. Bacterial Autoimmune Drug Metabolism Transforms an Immunomodulator into Structurally and Functionally Divergent Antibiotics Angewandte Chemie 2020, 132: 7945-7954. DOI: 10.1002/ange.201916204.
  • Abstract A103: Transcriptional profiles of CD14+ cells in situ in melanoma reveal plasticity, localization-dependent function, and specific T-cell interactionsMartinek J, in Kim K, Wu T, Boruchov H, Gulati A, Sun L, Wang V, George J, Henrich P, Marches F, Rongvaux A, Chiorazzi M, Chuang J, Robson P, Flavell R, Banchereau J, Palucka K. Abstract A103: Transcriptional profiles of CD14+ cells in situ in melanoma reveal plasticity, localization-dependent function, and specific T-cell interactions Cancer Immunology Research 2020, 8: a103-a103. DOI: 10.1158/2326-6074.tumimm19-a103.
  • Molecular Mechanisms of RNA Sensing in NLRP6 Inflammasome SignalingShen C, Li R, Negro R, Flavell R, Zhu S, Wu H. Molecular Mechanisms of RNA Sensing in NLRP6 Inflammasome Signaling Biophysical Journal 2020, 118: 202a. DOI: 10.1016/j.bpj.2019.11.1216.
  • Loss of METTL3 Mediated m6A RNA Modification Results in Double-Stranded RNA Induced Innate Immune Response and Hematopoietic FailureGao Y, Vasic R, Song Y, Teng R, Gbyli R, Biancon G, Nelakanti R, Kudo E, Liu W, Ardasheva A, Fu X, Wang X, Joshi P, Dura B, Lee V, Viero G, Iwasaki A, Fan R, Xiao A, Flavell R, Li H, Tebaldi T, Halene S. Loss of METTL3 Mediated m6A RNA Modification Results in Double-Stranded RNA Induced Innate Immune Response and Hematopoietic Failure Blood 2019, 134: 450-450. DOI: 10.1182/blood-2019-130442.
  • PARP Inhibitors Are Effective in IDH1/2 Mutant MDS and AML Resistant to Targeted IDH InhibitorsGbyli R, Song Y, Liu W, Gao Y, Chandhok N, Fu X, Wang X, Patel A, Sundaram R, Tebaldi T, Biancon G, Ardasheva A, Qin A, Sadykov M, Mamillapalli P, Flavell R, Prebet T, Bindra R, Halene S. PARP Inhibitors Are Effective in IDH1/2 Mutant MDS and AML Resistant to Targeted IDH Inhibitors Blood 2019, 134: 4222-4222. DOI: 10.1182/blood-2019-130814.
  • In Vivo reconstruction of Human Erythropoiesis with Circulating Mature Human RBCs in Humanized Liver Mistrg MiceSong Y, Shan L, Gbyli R, Liu W, Fu X, Wang X, Qin A, Patel A, Gao Y, Tebaldi T, Biancon G, Urbonas D, Alderman J, Halene S, Flavell R. In Vivo reconstruction of Human Erythropoiesis with Circulating Mature Human RBCs in Humanized Liver Mistrg Mice Blood 2019, 134: 338-338. DOI: 10.1182/blood-2019-130701.
  • Abstract 1507: Transcriptional profiles of CD14+ cells in situ in melanoma tumors reveal plasticity and localization dependent functionMartinek J, Kim K, Wu T, Wang V, Brookes H, Sun L, Gulati A, George J, Henrich P, Marches F, Rongvaux A, Chiorazzi M, Chuang J, Robson P, Flavell R, Banchereau J, Palucka K. Abstract 1507: Transcriptional profiles of CD14+ cells in situ in melanoma tumors reveal plasticity and localization dependent function 2019, 1507-1507. DOI: 10.1158/1538-7445.sabcs18-1507.
  • Abstract 1507: Transcriptional profiles of CD14+ cells in situ in melanoma tumors reveal plasticity and localization dependent functionMartinek J, Kim K, Wu T, Wang V, Brookes H, Sun L, Gulati A, George J, Henrich P, Marches F, Rongvaux A, Chiorazzi M, Chuang J, Robson P, Flavell R, Banchereau J, Palucka K. Abstract 1507: Transcriptional profiles of CD14+ cells in situ in melanoma tumors reveal plasticity and localization dependent function Cancer Research 2019, 79: 1507-1507. DOI: 10.1158/1538-7445.am2019-1507.
  • PS1439 ENHANCED SUPPORT OF MYELOFIBROSIS STEM CELLS IN NEXT GENERATION HUMANIZED MICELysenko V, Wildner N, Zimmermann K, Weller M, Schürch P, Fritz C, Calabresi L, Flavell R, Vannucchi A, Wild P, Dirnhofer S, Manz M, Theocharides A. PS1439 ENHANCED SUPPORT OF MYELOFIBROSIS STEM CELLS IN NEXT GENERATION HUMANIZED MICE HemaSphere 2019, 3: 663-664. DOI: 10.1097/01.hs9.0000564032.35865.cb.
  • To Code or Not to Code: What Is the Linc?Flavell R. To Code or Not to Code: What Is the Linc? The FASEB Journal 2019, 33: 218.1-218.1. DOI: 10.1096/fasebj.2019.33.1_supplement.218.1.
  • Mettl3 Mediated m6A Modification Is Essential in Fetal HematopoiesisGao Y, Vasic R, Tebaldi T, Song Y, Teng R, Joshi P, Viero G, Xiao A, Batista P, Li H, Flavell R, Halene S. Mettl3 Mediated m6A Modification Is Essential in Fetal Hematopoiesis Blood 2018, 132: 3825-3825. DOI: 10.1182/blood-2018-99-119699.
  • 632 - Immunoglobulin A-Coated Bacteria Represent a Unique Subset of the Microbiome in Patients with Newly Diagnosed Inflammatory Bowel DiseaseShapiro J, Clemente J, Palm N, de Zoete M, Laenen Y, Flavell R, Cho J, Bright R, Mallette M, Moniz H, Amaral K, Xu F, Hurtado-Lorenzo A, Shah S, Leleiko N, Sands B. 632 - Immunoglobulin A-Coated Bacteria Represent a Unique Subset of the Microbiome in Patients with Newly Diagnosed Inflammatory Bowel Disease Gastroenterology 2018, 154: s-132-s-133. DOI: 10.1016/s0016-5085(18)30869-2.
  • Abstract A071: Identification and characterization of long intergenic non-coding RNAs (lincRNAs) governing T cell development and functionBailis W, Harman C, Henao-Mejia J, Williams A, Goff L, Rinn J, Flavell R. Abstract A071: Identification and characterization of long intergenic non-coding RNAs (lincRNAs) governing T cell development and function Cancer Immunology Research 2016, 4: a071-a071. DOI: 10.1158/2326-6066.imm2016-a071.
  • Abstract B088: Can the pro-tumorigenic activity of Th17 cells be a therapeutic opportunity?Gagliani N, Vasely C, Xu H, Huber S, Flavell R. Abstract B088: Can the pro-tumorigenic activity of Th17 cells be a therapeutic opportunity? Cancer Immunology Research 2016, 4: b088-b088. DOI: 10.1158/2326-6074.cricimteatiaacr15-b088.
  • Efficient Engraftment and Disease Replication of Myelodysplastic Syndromes Using a Novel Humanized Mice ModelSong Y, Taylor A, Rongvaux A, Jiang T, Podoltsev N, Xu M, Neparidze N, Torres R, Barbarotta L, Balasubramanian K, Finberg K, Kluger Y, Flavell R, Halene S. Efficient Engraftment and Disease Replication of Myelodysplastic Syndromes Using a Novel Humanized Mice Model Blood 2015, 126: 4100-4100. DOI: 10.1182/blood.v126.23.4100.4100.
  • Developing a Model of Human Pluripotent to Hematopoietic Stem Cell Development in Mistrg MiceAstle J, Xiang Y, Rongvaux A, Weibel C, Elizabeth H, Halene S, Park I, Flavell R. Developing a Model of Human Pluripotent to Hematopoietic Stem Cell Development in Mistrg Mice Blood 2015, 126: 4755-4755. DOI: 10.1182/blood.v126.23.4755.4755.
  • Niche-Dependent Growth of Malignant and Pre-Neoplastic Plasma Cells in Humanized MiceDas R, Strowig T, Verma R, Koduru S, Hafemann A, Hopf S, Kocoglu M, Borsotti C, Zhang L, Branagan A, Eynon E, Manz M, Flavell R, Dhodapkar M. Niche-Dependent Growth of Malignant and Pre-Neoplastic Plasma Cells in Humanized Mice Blood 2015, 126: 120-120. DOI: 10.1182/blood.v126.23.120.120.
  • Humanized Mouse Model of Myeloma Reveals Clinically Occult Genomic Changes in Primary Tumor CellsVerma R, Strowig T, Das R, Koduru S, Hafemann A, Hopf S, Kocoglu M, Borsotti C, Zhang L, Branagan A, Eynon E, Manz M, Flavell R, Dhodapkar M. Humanized Mouse Model of Myeloma Reveals Clinically Occult Genomic Changes in Primary Tumor Cells Blood 2015, 126: 22-22. DOI: 10.1182/blood.v126.23.22.22.
  • Abstract 19446: Role of miR-181 Family in the Heart: A Tale of Two Intracellular CompartmentsDas S, Kohr M, Dunkerly B, Bedja D, Kent O, Leung A, Henao-Mejia J, Flavell R, Steenbergen C. Abstract 19446: Role of miR-181 Family in the Heart: A Tale of Two Intracellular Compartments Circulation 2015, 132 DOI: 10.1161/circ.132.suppl_3.19446.
  • 26 HUMANIZED MICE AFFORD EFFICIENT ENGRAFTMENT AND DISEASE REPLICATION OF MYELODYSPLASTIC SYNDROMESSong Y, Rongvaux A, Taylor A, Podoltsev N, Xu M, Neparidze N, Torres R, Barbarotta L, Balasubramanian K, Finberg K, Flavell R, Halene S. 26 HUMANIZED MICE AFFORD EFFICIENT ENGRAFTMENT AND DISEASE REPLICATION OF MYELODYSPLASTIC SYNDROMES Leukemia Research 2015, 39: s11-s12. DOI: 10.1016/s0145-2126(15)30027-8.
  • ΜΙSΤRG Mice Support Good-Risk AML EngraftmentEllegast J, Saito Y, Flavell R, Manz M. ΜΙSΤRG Mice Support Good-Risk AML Engraftment Blood 2014, 124: 3808-3808. DOI: 10.1182/blood.v124.21.3808.3808.
  • Antivirulence Properties of an Antifreeze ProteinHeisig M, Abraham N, Liu L, Neelakanta G, Mattessich S, Sultana H, Shang Z, Ansari J, Killiam C, Walker W, Cooley L, Flavell R, Agaisse H, Fikrig E. Antivirulence Properties of an Antifreeze Protein Cell Reports 2014, 9: 2344. DOI: 10.1016/j.celrep.2014.12.003.
  • Erratum: Corrigendum: TH2, allergy and group 2 innate lymphoid cellsLicona-Limón P, Kim L, Palm N, Flavell R. Erratum: Corrigendum: TH2, allergy and group 2 innate lymphoid cells Nature Immunology 2013, 15: 109-109. DOI: 10.1038/ni0114-109d.
  • Inflammasomes and Mucosal Immune ResponseElinav E, Henao-Mejia J, Flavell R. Inflammasomes and Mucosal Immune Response 2013, 4: 48-52. DOI: 10.1159/000346510.
  • Microbiota Keep the Intestinal Clock TickingHenao-Mejia J, Strowig T, Flavell R. Microbiota Keep the Intestinal Clock Ticking Cell 2013, 153: 1612. DOI: 10.1016/j.cell.2013.05.045.
  • P-225 Modeling of myelodysplasia in a humanized immunodeficient mouse modelHalene S, Rongvaux A, Podoltsev N, Kahlon K, Manz M, Flavell R. P-225 Modeling of myelodysplasia in a humanized immunodeficient mouse model Leukemia Research 2013, 37: s124-s125. DOI: 10.1016/s0145-2126(13)70272-8.
  • DNA synthesis by isolated mitochondria III. Characterization of D-loop DNA, a novel intermediate in mtDNA synthesisSchegget J, Flavell R, Borst P. DNA synthesis by isolated mitochondria III. Characterization of D-loop DNA, a novel intermediate in mtDNA synthesis Biochimica Et Biophysica Acta (BBA) - Nucleic Acids And Protein Synthesis 1971, 254: 1-14. DOI: 10.1016/0005-2787(71)90109-2.