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Lucchesi, Carolina

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Lucchesi

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Carolina

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Lucchesi, Carolina

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2013 - 20152

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Author's Publications: search.filters.isAuthorOfPublication.96f7f73a-14f8-4098-85ba-e120f4416b85

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    On the design of clone-based haplotyping
    (BioMed Central, 2013) Lo, Christine; Liu, Rui; Lee, Jehyuk; Robasky, Kimberly; Byrne, Susan M; Lucchesi, Carolina; Aach, John; Church, George; Bafna, Vineet; Zhang, Kun
    Background: Haplotypes are important for assessing genealogy and disease susceptibility of individual genomes, but are difficult to obtain with routine sequencing approaches. Experimental haplotype reconstruction based on assembling fragments of individual chromosomes is promising, but with variable yields due to incompletely understood parameter choices. Results: We parameterize the clone-based haplotyping problem in order to provide theoretical and empirical assessments of the impact of different parameters on haplotype assembly. We confirm the intuition that long clones help link together heterozygous variants and thus improve haplotype length. Furthermore, given the length of the clones, we address how to choose the other parameters, including number of pools, clone coverage and sequencing coverage, so as to maximize haplotype length. We model the problem theoretically and show empirically the benefits of using larger clones with moderate number of pools and sequencing coverage. In particular, using 140 kb BAC clones, we construct haplotypes for a personal genome and assemble haplotypes with N50 values greater than 2.6 Mb. These assembled haplotypes are longer and at least as accurate as haplotypes of existing clone-based strategies, whether in vivo or in vitro. Conclusions: Our results provide practical guidelines for the development and design of clone-based methods to achieve long range, high-resolution and accurate haplotypes.
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    Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro
    (Nature Publishing Group, 2015) Benam, Kambez H; Villenave, Remi; Lucchesi, Carolina; Varone, Antonio; Hubeau, Cedric; Lee, Hyun-Hee; Alves, Stephen E; Salmon, Michael; Ferrante, Thomas; Weaver, James; Bahinski, Anthony; Hamilton, Geraldine A; Ingber, Donald
    Here we describe development of a human ‘lung small airway-on-a-chip’ containing a differentiated, mucociliary, bronchiolar epithelium and an underlying microvascular endothelium that experiences fluid flow, which enables analysis of organ-level lung pathophysiology in vitro. Exposure of the epithelium to IL-13 reconstitutes the goblet cell hyperplasia, cytokine hypersecretion and decreased ciliary function of asthmatics. Small airway chips lined by epithelial cells from chronic obstructive pulmonary disease patients recapitulate features of the disease including selective cytokine hypersecretion, increased neutrophil recruitment, and clinical exacerbations by exposure to viral and bacterial infections. Using this robust in vitro method for modeling human lung inflammatory disorders, it is possible to detect synergistic effects of lung endothelium and epithelium on cytokine secretion, identify new biomarkers of disease exacerbation, and measure therapeutic responses to anti-inflammatory compounds that inhibit cytokine-induced recruitment of circulating neutrophils under flow.