1. Pathogen Cell-to-Cell Variability Drives Heterogeneity in Host Immune Responses

    Cell 163(2):523 (2015)

  2. Pathogen Cell-to-Cell Variability Drives Heterogeneity in Host Immune Responses.

    Cell 162(6):1309 (2015) PMID 26343579 PMCID PMC4578813

    Encounters between immune cells and invading bacteria ultimately determine the course of infection. These interactions are usually measured in populations of cells, masking cell-to-cell variation that may be important for infection outcome. To characterize the gene expression variation that unde...
  3. Aberrant innate immune activation following tissue injury impairs pancreatic regeneration.

    PLoS ONE 9(7):e102125 (2014) PMID 25010227 PMCID PMC4092101

    Normal tissue architecture is disrupted following injury, as resident tissue cells become damaged and immune cells are recruited to the site of injury. While injury and inflammation are critical to tissue remodeling, the inability to resolve this response can lead to the destructive complication...
  4. Production of α-galactosylceramide by a prominent member of the human gut microbiota.

    PLoS Biology 11(7):e1001610 (2013) PMID 23874157 PMCID PMC3712910

    While the human gut microbiota are suspected to produce diffusible small molecules that modulate host signaling pathways, few of these molecules have been identified. Species of Bacteroides and their relatives, which often comprise >50% of the gut community, are unusual among bacteria in that th...
  5. IL-7 receptor blockade reverses autoimmune diabetes by promoting inhibition of effector/memory T cells.

    PNAS 109(31):12668 (2012) PMID 22733744 PMCID PMC3411948

    To protect the organism against autoimmunity, self-reactive effector/memory T cells (T(E/M)) are controlled by cell-intrinsic and -extrinsic regulatory mechanisms. However, how some T(E/M) cells escape regulation and cause autoimmune disease is currently not understood. Here we show that blockin...
  6. Anti-CD3 therapy promotes tolerance by selectively depleting pathogenic cells while preserving regulatory T cells.

    Journal of Immunology 187(4):2015 (2011) PMID 21742976 PMCID PMC3150219

    Monoclonal anti-CD3 Abs have been used clinically for two decades to reverse steroid-resistant acute graft rejection. In autoimmune diabetes, short course treatment with FcR-nonbinding (FNB) anti-CD3 mAb in mice with recent onset of diabetes induces long-term disease remission. Induction of tole...
  7. Intrinsic and extrinsic control of peripheral T-cell tolerance by costimulatory molecules of the CD28/ B7 family.

    Immunological Reviews 241(1):180 (2011) PMID 21488898 PMCID PMC3077803

    Positive and negative costimulation by members of the CD28 family is critical for the development of productive immune responses against foreign pathogens and their proper termination to prevent inflammation-induced tissue damage. In addition, costimulatory signals are critical for the establish...
  8. Prevention of diabetes by FTY720-mediated stabilization of peri-islet tertiary lymphoid organs.

    Diabetes 59(6):1461 (2010) PMID 20299465 PMCID PMC2874707

    The nonobese diabetic (NOD) mouse is a well-established mouse model of spontaneous type 1 diabetes, which is characterized by an autoimmune destruction of the insulin-secreting pancreatic beta-cells. In this study, we address the role of tertiary lymphoid organs (TLOs) that form in the pancreas ...
  9. Is antigen specificity of autoreactive T cells the key to islet entry?

    Immunity 31(4):534 (2009) PMID 19833083

    It has been widely hypothesized that pancreatic islet infiltrates include both islet-antigen-specific and nonspecific T cells. In this issue of Immunity, Lennon et al. (2009) demonstrate that islet-antigen specificity is required for accumulation in the islets.
  10. Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo.

    Nature Immunology 10(9):1000 (2009) PMID 19633673 PMCID PMC2729804

    Regulatory T cells (T(reg) cells) are central to the maintenance of immune homeostasis. However, little is known about the stability of T(reg) cells in vivo. In this study, we demonstrate that a substantial percentage of cells had transient or unstable expression of the transcription factor Foxp...
  11. Central role of defective interleukin-2 production in the triggering of islet autoimmune destruction.

    Immunity 28(5):687 (2008) PMID 18468463 PMCID PMC2394854

    The dynamics of CD4(+) effector T cells (Teff cells) and CD4(+)Foxp3(+) regulatory T cells (Treg cells) during diabetes progression in nonobese diabetic mice was investigated to determine whether an imbalance of Treg cells and Teff cells contributes to the development of type 1 diabetes. Our res...
  12. Inhibition of IGF-1R and lipoxygenase by nordihydroguaiaretic acid (NDGA) analogs.

    Bioorganic & Medicinal Chemistry Letters 17(14):4026 (2007) PMID 17502145 PMCID PMC2253493

    Herein, we pursue the hypothesis that the structure of nordihydroguaiaretic acid (NDGA) can be refined for selective potency against the insulin-like growth factor 1 receptor (IGF-1R) as a potential therapeutic target for breast cancer while diminishing its action against other cellular targets....
  13. Inhibition of IGF-1R and lipoxygenase by nordihydroguaiaretic acid (NDGA) analogs

    Bioorganic & Medicinal Chemistry Letters 17(14):4026 (2007)

  14. In Vivo and In Silico Modeling the Dynamics of Autoimmune Diabetes

    Clinical Immunology 123:S70 (2007)

  15. Diarylureas are small-molecule inhibitors of insulin-like growth factor I receptor signaling and breast cancer cell growth.

    Molecular Cancer Therapeutics 5(4):1079 (2006) PMID 16648580

    In breast and certain other cancers, receptor tyrosine kinases, including the insulin-like growth factor I receptor (IGF-IR), play an important role in promoting the oncogenic process. The IGF-IR is therefore an important target for developing new anti-breast cancer therapies. An initial screeni...
  16. Parallel synthesis of diarylureas and their evaluation as inhibitors of insulin-like growth factor receptor.

    Journal of Combinatorial Chemistry 8(5):784 (2006) PMID 16961415

    Diarylurea (DAU) compounds, particularly species composed of a heteroaryl ring system conjugated through a urea linkage to a substituted arene, were previously identified by the screening of a diverse chemical library to be active against the insulin growth factor receptor (IGF-1R). DAU compound...
  17. Nordihydroguaiaretic acid (NDGA) inhibits the IGF-1 and c-erbB2/HER2/neu receptors and suppresses growth in breast cancer cells.

    Breast Cancer Research and Treatment 94(1):37 (2005) PMID 16142439

    Nordihydroguaiaretic acid (NDGA) is a phenolic compound isolated from the creosote bush Larrea divaricatta that has anti-cancer activities both in vitro and in vivo. We can now attribute certain of these anti-cancer properties in breast cancer cells to the ability of NDGA to directly inhibit the...
  18. T-bet is required for optimal production of IFN-gamma and antigen-specific T cell activation by dendritic cells.

    PNAS 100(13):7749 (2003) PMID 12802010 PMCID PMC164659

    IFN-gamma is well known as the signature cytokine of CD4+ T helper 1, CD8+, and natural killer cells, but recent studies demonstrate that antigen-presenting cells, in particular dendritic cells (DCs), are another potent source for this proinflammatory cytokine. T-bet, a transcription factor that...