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Calamari, Elizabeth

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Calamari

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Elizabeth

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Calamari, Elizabeth
Author's Publications: search.filters.isAuthorOfPublication.f82919af-fb75-4628-afd3-c3e3432ec7a2

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    A Complex Human-Gut Microbiome Cultured in an Anaerobic Intestine-on-a-Chip
    (‎Nature Research, 2019-07) Jalili-Firoozinezhad, Sasan; Gazzaniga, Francesca; Calamari, Elizabeth; Camacho, Diogo; Fadel, Cicely; Bein, Amir; Swenor, Ben; Nestor, Bret; Cronce, Michael; Levy, Oren; Gregory, Katherine; Breault, David; Cabral, Joaquim; Novak, Richard; Kasper, Dennis; Tovaglieri, Alessio; Ingber, Donald
    The diverse bacterial populations that comprise the commensal microbiome of the human intestine play a central role in health and disease. A method that sustains complex microbial communities in direct contact with living human intestinal cells and their overlying mucus layer in vitro would thus enable the investigation of host–microbiome interactions. Here, we show the extended coculture of living human intestinal epithelium with stable communities of aerobic and anaerobic human gut microbiota, using a microfluidic intestine-on-a-chip that permits the control and real-time assessment of physiologically relevant oxygen gradients. When compared to aerobic coculture conditions, the establishment of a transluminal hypoxia gradient in the chip increased intestinal barrier function and sustained a physiologically relevant level of microbial diversity, consisting of over 200 unique operational taxonomic units from 11 different genera and an abundance of obligate anaerobic bacteria, with ratios of Firmicutes and Bacteroidetes similar to those observed in human faeces. The intestine-on-a-chip may serve as a discovery tool for the development of microbiome-related therapeutics, probiotics and nutraceuticals.
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    On-chip recapitulation of clinical bone marrow toxicities and patient-specific pathophysiology
    (Springer Science and Business Media LLC, 2020-01-27) Chou, David; Frismantas, Viktoras; Milton, Yuka; David, Rhiannon; Pop-Damkov, Petar; Ferguson, Douglas; MacDonald, Alexander; Vargel Bolukbasi, Ozge; Joyce, Cailin E.; Moreira Teixeira, Liliana S.; Rech, Arianna; Jiang, Amanda; Calamari, Elizabeth; Jalili-Firoozinezhad, Sasan; Furlong, Brooke; O’Sullivan, Lucy R.; Ng, Carlos F.; Choe, Youngjae; Marquez, Susan; Myers, Kasiani C.; Weinberg, Olga K.; Hasserjian, Robert; Novak, Richard; Levy, Oren; Prantil-Baun, Rachelle; Novina, Carl; Shimamura, Akiko; Ewart, Lorna; Ingber, Donald
    The inaccessibility of living bone marrow hampers the study of its pathophysiology under myelotoxic stress induced by drugs, radiation or genetic mutations. Here, we show that a vascularized human bone-marrow-on-a-chip supports the differentiation and maturation of multiple blood-cell lineages over 4 weeks while improving CD34+ cell maintenance, and that it recapitulates aspects of marrow injury, including myeloerythroid toxicity after clinically relevant exposures to chemotherapeutic drugs and ionizing radiation as well as marrow recovery after drug-induced myelosuppression. The chip comprises a fluidic channel filled with a fibrin gel in which CD34+ cells and bone-marrow-derived stromal cells are co-cultured, a parallel channel lined by human vascular endothelium and perfused with culture medium, and a porous membrane separating the two channels. We also show that bone-marrow chips containing cells from patients with the rare genetic disorder Shwachman–Diamond syndrome reproduced key haematopoietic defects and led to the discovery of a neutrophil-maturation abnormality. As an in vitro model of haematopoietic dysfunction, the bone-marrow-on-a-chip may serve as a human-specific alternative to animal testing for the study of bone-marrow pathophysiology.
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    Publication
    Robotic fluidic coupling and interrogation of multiple vascularized organ chips
    (Springer Science and Business Media LLC, 2020-01-27) Novak, Richard; Ingram, Miles; Marquez, Susan; Das, Debarun; Delahanty, Aaron; Herland, Anna; Maoz, Ben; Jeanty, Sauveur; Somayaji, Mahadevabharath R.; Burt, Morgan; Calamari, Elizabeth; Chalkiadaki, Angeliki; Cho, Alexander; Choe, Youngjae; Chou, David; Cronce, Michael; Dauth, Stephanie; Divic, Toni; Fernandez-Alcon, Jose; Ferrante, Thomas; Ferrier, John; FitzGerald, Edward; Fleming, Rachel; Jalili Firoozinezhad, Sasan; Grevesse, Thomas; Goss, Josue; Hamkins-Indik, Tiama; Henry, Olivier; Hinojosa, Chris; Huffstater, Tessa; Jang, Kyung-Jin; Kujala, Ville; Leng, Lian; Mannix, Robert; Milton, Yuka; Nawroth, Janna; Nestor, Bret; Ng Pitti, Carlos; O'Connor, Blakely; Park, Tae-Eun; Sanchez, Henry; Sliz, Josiah; Sontheimer-Phelps, Alexandra; Swenor, Ben; Thompson, Guy; Touloumes, George J.; Tranchemontagne, Zachary; Wen, Norman; Yedid, Moran; Bahinski, Anthony; Hamilton, Geraldine; Levner, Daniel; Levy, Oren; Przekwas, Andrzej; Prantil-Baun, Rachelle; Parker, Kevin; Ingber, Donald
    Organ chips can recapitulate organ-level (patho)physiology, yet pharmacokinetic and pharmacodynamic analyses require multi-organ systems linked by vascular perfusion. Here, we describe an ‘Interrogator’ employing liquid-handling robotics, custom software and an integrated mobile microscope for the automated culture, perfusion, medium addition, fluidic linking, sample collection and in situ microscopic imaging of up to 10 Organ Chips inside a standard tissue-culture incubator. The robotic interrogator maintained the viability and organ-specific functions of eight vascularized, two-channel organ chips (intestine, liver, kidney, heart, lung, skin, blood–brain barrier and brain) for 3 weeks in culture when intermittently fluidically coupled via a common blood substitute through their medium reservoirs and endothelium-lined vascular channels. We used the robotic interrogator and a physiological multi-compartmental reduced-order model of the experimental system to quantitatively predict the distribution of an inulin tracer perfused through the multi-organ Human-Body-on-Chips. The automated culture system allows for the imaging of cells in the organ chips, and for repeated sampling of both the vascular and interstitial compartments without compromising fluidic coupling.