1. A highly multiplexed and sensitive RNA-seq protocol for simultaneous analysis of host and pathogen transcriptomes.

    Nature Protocols 11(8):1477 (2016) PMID 27442864

    The ability to simultaneously characterize the bacterial and host expression programs during infection would facilitate a comprehensive understanding of pathogen-host interactions. Although RNA sequencing (RNA-seq) has greatly advanced our ability to study the transcriptomes of prokaryotes and e...
  2. Pathogen Cell-to-Cell Variability Drives Heterogeneity in Host Immune Responses

    Cell 163(2):523 (2015)

  3. 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...
  4. Pharyngeal mesoderm regulatory network controls cardiac and head muscle morphogenesis.

    PNAS 109(46):18839 (2012) PMID 23112163 PMCID PMC3503185

    The search for developmental mechanisms driving vertebrate organogenesis has paved the way toward a deeper understanding of birth defects. During embryogenesis, parts of the heart and craniofacial muscles arise from pharyngeal mesoderm (PM) progenitors. Here, we reveal a hierarchical regulatory ...
  5. Context-specific microRNA analysis: identification of functional microRNAs and their mRNA targets.

    Nucleic Acids Research 40(21):10614 (2012) PMID 22977182 PMCID PMC3505984

    MicroRNAs (miRs) function primarily as post-transcriptional negative regulators of gene expression through binding to their mRNA targets. Reliable prediction of a miR's targets is a considerable bioinformatic challenge of great importance for inferring the miR's function. Sequence-based predicti...
  6. miR-10b*, a master inhibitor of the cell cycle, is down-regulated in human breast tumours.

    Embo Molecular Medicine 4(11):1214 (2012) PMID 23125021 PMCID PMC3494877

    Deregulated proliferation is a hallmark of cancer cells. Here, we show that microRNA-10b* is a master regulator of breast cancer cell proliferation and is downregulated in tumoural samples versus matched peritumoural counterparts. Two canonical CpG islands (5 kb) upstream from the precursor sequ...
  7. EGR1 and the ERK-ERF axis drive mammary cell migration in response to EGF.

    FASEB Journal 26(4):1582 (2012) PMID 22198386 PMCID PMC3316897

    The signaling pathways that commit cells to migration are incompletely understood. We employed human mammary cells and two stimuli: epidermal growth factor (EGF), which induced cellular migration, and serum factors, which stimulated cell growth. In addition to strong activation of ERK by EGF, an...
  8. A crossroad of microRNAs and immediate early genes (IEGs) encoding oncogenic transcription factors in breast cancer.

    Journal of Mammary Gland Biology and Neoplasia 17(1):3 (2012) PMID 22327345

    Signaling networks are involved in development, as well as in malignancy of the mammary gland. Distinct external stimuli activate intricate signaling cascades, which culminate in the activation of specific transcriptional programs. These signal-specific transcriptional programs are instigated by...
  9. Regulation of signalling by microRNAs.

    Biochemical Society Transactions 40(1):26 (2012) PMID 22260661 PMCID PMC3621035

    Stringent regulation of biochemical signalling pathways involves feedback and feedforward loops, which underlie robust cellular responses to external stimuli. Regulation occurs in all horizontal layers of signalling networks, primarily by proteins that mediate internalization of receptor-ligand ...
  10. Silencing of a large microRNA cluster on human chromosome 14q32 in melanoma: biological effects of mir-376a and mir-376c on insulin growth factor 1 receptor.

    Molecular Cancer 11:44 (2012) PMID 22747855 PMCID PMC3444916

    Metastatic melanoma is a devastating disease with limited therapeutic options. MicroRNAs (miRNAs) are small non coding RNA molecules with important roles in post-transcriptional gene expression regulation, whose aberrant expression has been implicated in cancer. We show that the expression of mi...
  11. Two phases of mitogenic signaling unveil roles for p53 and EGR1 in elimination of inconsistent growth signals.

    Molecular Cell 42(4):524 (2011) PMID 21596316 PMCID PMC3100487

    Normal cells require continuous exposure to growth factors in order to cross a restriction point and commit to cell-cycle progression. This can be replaced by two short, appropriately spaced pulses of growth factors, where the first pulse primes a process, which is completed by the second pulse,...
  12. Two phases of mitogenic signaling unveil roles for p53 and EGR1 in elimination of inconsistent growth signals.

    Molecular Cell 42(4):524 (2011) PMID 21596316 PMCID PMC3100487

    Normal cells require continuous exposure to growth factors in order to cross a restriction point and commit to cell-cycle progression. This can be replaced by two short, appropriately spaced pulses of growth factors, where the first pulse primes a process, which is completed by the second pulse,...
  13. Two phases of mitogenic signaling unveil roles for p53 and EGR1 in elimination of inconsistent growth signals.

    Molecular Cell 42(4):524 (2011) PMID 21596316 PMCID PMC3100487

    Normal cells require continuous exposure to growth factors in order to cross a restriction point and commit to cell-cycle progression. This can be replaced by two short, appropriately spaced pulses of growth factors, where the first pulse primes a process, which is completed by the second pulse,...
  14. Feedback regulation of EGFR signalling: decision making by early and delayed loops.

    Nature Reviews: Molecular Cell Biology 12(2):104 (2011) PMID 21252999

    Human-made information relay systems invariably incorporate central regulatory components, which are mirrored in biological systems by dense feedback and feedforward loops. This type of system control is exemplified by positive and negative feedback loops (for example, receptor endocytosis and d...
  15. Do stress responses promote leukemia progression? An animal study suggesting a role for epinephrine and prostaglandin-E2 through reduced NK activity.

    PLoS ONE 6(4):e19246 (2011) PMID 21559428 PMCID PMC3084788

    In leukemia patients, stress and anxiety were suggested to predict poorer prognosis. Oncological patients experience ample physiological and psychological stress, potentially leading to increased secretion of stress factors, including epinephrine, corticosteroids, and prostaglandins. Here we tes...
  16. Two Phases of Mitogenic Signaling Unveil Roles for p53 and EGR1 in Elimination of Inconsistent Growth Signals

    Molecular Cell 42(4):524 (2011) PMID 21596316 PMCID PMC3100487

    Normal cells require continuous exposure to growth factors in order to cross a restriction point and commit to cell-cycle progression. This can be replaced by two short, appropriately spaced pulses of growth factors, where the first pulse primes a process, which is completed by the second p...
  17. Synergism between immunostimulation and prevention of surgery-induced immune suppression: an approach to reduce post-operative tumor progression.

    Brain, Behavior, and Immunity 24(6):952 (2010) PMID 20362661 PMCID PMC2897966

    A unique opportunity to eradicate cancer is presented immediately after the excision of the primary tumor, but surgical procedures often induce the release of immunosuppressing factors that render cell mediated immunity ineffective. Here we tested the hypothesis that integration of peri-operativ...
  18. Improving survival rates in two models of spontaneous postoperative metastasis in mice by combined administration of a beta-adrenergic antagonist and a cyclooxygenase-2 inhibitor.

    Journal of Immunology 184(5):2449 (2010) PMID 20124103

    Clinical practice does not consider perioperative paracrine and neuroendocrine stress responses as risk factors for cancer recurrence, although recent animal studies provided supportive evidence. Suggested mechanisms include the effects of stress-hormones on tumor cells and on host physiology. I...
  19. EGF decreases the abundance of microRNAs that restrain oncogenic transcription factors.

    Science Signaling 3(124):ra43 (2010) PMID 20516477

    Epidermal growth factor (EGF) stimulates cells by launching gene expression programs that are frequently deregulated in cancer. MicroRNAs, which attenuate gene expression by binding complementary regions in messenger RNAs, are broadly implicated in cancer. Using genome-wide approaches, we showed...
  20. Blood transfusion promotes cancer progression: a critical role for aged erythrocytes.

    Anesthesiology 109(6):989 (2008) PMID 19034095 PMCID PMC2694914

    In cancer patients, allogeneic blood transfusion is associated with poorer prognosis, but the independent effect of the transfusion is controversial. Moreover, mediating mechanisms underlying the alleged cancer-promoting effects of blood transfusion are unknown, including the involvement of dono...