All Publications


  • Ferroptosis-like death in plant cells. Molecular & cellular oncology Conlon, M., Dixon, S. J. 2017; 4 (3): e1302906

    Abstract

    Ferroptosis is an iron-dependent, oxidative, non-apoptotic form of cell death initially described in mammalian cells. We recently reported that a ferroptosis-like cell death process can be triggered by heat shock in Arabidopsis thaliana. Thus, ferroptosis may be a form of cell death conserved between animals and plants.

    View details for DOI 10.1080/23723556.2017.1302906

    View details for PubMedID 28616580

    View details for PubMedCentralID PMC5462507

  • Systematic Quantification of Population Cell Death Kinetics in Mammalian Cells. Cell systems Forcina, G. C., Conlon, M., Wells, A., Cao, J. Y., Dixon, S. J. 2017; 4 (6): 600–610.e6

    Abstract

    Cytotoxic compounds are important drugs and research tools. Here, we introduce a method, scalable time-lapse analysis of cell death kinetics (STACK), to quantify the kinetics of compound-induced cell death in mammalian cells at the population level. STACK uses live and dead cell markers, high-throughput time-lapse imaging, and mathematical modeling to determine the kinetics of population cell death over time. We used STACK to profile the effects of over 1,800 bioactive compounds on cell death in two human cancer cell lines, resulting in a large and freely available dataset. 79 potent lethal compounds common to both cell lines caused cell death with widely divergent kinetics. 13 compounds triggered cell death within hours, including the metallophore zinc pyrithione. Mechanistic studies demonstrated that this rapid onset lethal phenotype was caused in human cancer cells by metabolic disruption and ATP depletion. These results provide the first comprehensive survey of cell death kinetics and analysis of rapid-onset lethal compounds.

    View details for DOI 10.1016/j.cels.2017.05.002

    View details for PubMedID 28601558

    View details for PubMedCentralID PMC5509363

  • Early pancreatic islet fate and maturation is controlled through RBP-J?. Scientific reports Cras-Méneur, C., Conlon, M., Zhang, Y., Pasca di Magliano, M., Bernal-Mizrachi, E. 2016; 6: 26874-?

    Abstract

    Notch signaling is known to control early pancreatic differentiation through Ngn3 repression. In later stages, downstream of Notch, the Presenilins are still required to maintain the endocrine fate allocation. Amongst their multiple targets, it remains unclear which one actually controls the maintenance of the fate of the early islets. Conditional deletions of the Notch effector RBP-Jκ with lineage tracing in Presenilin-deficient endocrine progenitors, demonstrated that this factor is central to the control of the fate through a non-canonical Notch mechanism. RBP-Jκ mice exhibit normal islet morphogenesis and function, however, a fraction of the progenitors fails to differentiate and develop into disorganized masses resembling acinar to ductal metaplasia and chronic pancreatitis. A subsequent deletion of RBP-Jκ in forming β-cells led to the transdifferentiation into the other endocrine cells types, indicating that this factor still mediates the maintenance of the fate within the endocrine lineage itself. These results highlight the dual importance of Notch signaling for the endocrine lineage. Even after Ngn3 expression, Notch activity is required to maintain both fate and maturation of the Ngn3 progenitors. In a subset of the cells, these alterations of Notch signaling halt their differentiation and leads to acinar to ductal metaplasia.

    View details for DOI 10.1038/srep26874

    View details for PubMedID 27240887

    View details for PubMedCentralID PMC4886527

  • Plasma CXCL9 elevations correlate with chronic GVHD diagnosis BLOOD Kitko, C. L., Levine, J. E., Storer, B. E., Chai, X., Fox, D. A., Braun, T. M., Couriel, D. R., Martin, P. J., Flowers, M. E., Hansen, J. A., Chang, L., Conlon, M., Fiema, B. J., Morgan, R., Pongtornpipat, P., Lamiman, K., Ferrara, J. L., Lee, S. J., Paczesny, S. 2014; 123 (5): 786-793

    Abstract

    There are no validated biomarkers for chronic GVHD (cGVHD). We used a protein microarray and subsequent sequential enzyme-linked immunosorbent assay to compare 17 patients with treatment-refractory de novo-onset cGVHD and 18 time-matched control patients without acute or chronic GVHD to identify 5 candidate proteins that distinguished cGVHD from no cGVHD: CXCL9, IL2Rα, elafin, CD13, and BAFF. We then assessed the discriminatory value of each protein individually and in composite panels in a validation cohort (n = 109). CXCL9 was found to have the highest discriminatory value with an area under the receiver operating characteristic curve of 0.83 (95% confidence interval, 0.74-0.91). CXCL9 plasma concentrations above the median were associated with a higher frequency of cGVHD even after adjustment for other factors related to developing cGVHD including age, diagnosis, donor source, and degree of HLA matching (71% vs 20%; P < .001). A separate validation cohort from a different transplant center (n = 211) confirmed that CXCL9 plasma concentrations above the median were associated with more frequent newly diagnosed cGVHD after adjusting for the aforementioned factors (84% vs 60%; P = .001). Our results confirm that CXCL9 is elevated in patients with newly diagnosed cGVHD.

    View details for DOI 10.1182/blood-2013-08-520072

    View details for Web of Science ID 000335832500032

    View details for PubMedID 24363401

    View details for PubMedCentralID PMC3907763