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Janna Nawroth - Mechanobiology
Our research focuses on the development of organ-on-chip systems, i.e. human organotypic microtissues cultured in a mechanically active microenvironment that mimics physiological cues and forces, such as fluid shear stresses, confinements, and strain. Organ-on-chip systems also support tissue interfaces, such as between epithelia, endothelia, and connective tissues, as well as integration of immune cell components, such as neutrophils and macrophages. These mechanical and biological components, which are missing in traditional tissue models, have been shown to significantly alter cellular biology and are thought to play important roles in differentiation, regeneration, and disease processes, including immunity and cancer. We have recently shown the application of a multi-cell type liver chip model to studying complex pathological processes in alcohol-associated liver disease, a common precursor to liver cancer. We currently focus on developing two vascularized human airway chip models that, in structure, cellular composition, and barrier function, more accurately mimic the trachea-bronchial and the small-airway regions of the lung than traditional model systems. We then aim to challenge this complex model with inflammatory conditions and carcinogenic agents, including cigarette smoke extract, to better understand the mal-adaptive responses of the airways underlying chronic disease. To assess responses of the tissues, we develop and adapt quantitative imaging methods to measure structural and mechanical changes at multiple spatial and temporal scales and combine these with molecular and genetic assays, such as ELISA and qPCR, respectively. In the future, patient-specific organ-on-chip models could be used to study personalized treatment options in specific patient cohorts, including cancer treatments and gene therapy.
Our main research projects are:
- Development of organotypic human airway chip models with physiological barrier function and immune responses.
- Integration of chip models in cancer discovery and treatment pipelines, linking controlled biological responses with advanced observation techniques.
- Further development of physics-based computational models for understanding the role of mechanobiological processes in function and dysfunction.
Janna Nawroth received her PhD in Biology at the California Institute of Technology, where she studied the structure-function relationships of jellyfish propulsion and used these insights to engineer muscle powered pumps for biomedical research. For her postdoctoral training, she was awarded the Technology Development Fellowship at the Harvard University Wyss Institute. She developed Organ-Chips and advanced imaging technologies with Don Ingber and Kit Parker to study the mechanics of human heart, lung and liver tissues, before continuing this work at the Organ-Chip company Emulate and later at the University of Southern California. In 2020, Dr. Nawroth received an ERC Starting grant for studying the role of mechanical forces and defective mucociliary clearance in chronic airway disease. In 2021, Dr. Nawroth joined the Helmholtz Pioneer Campus.
Nawroth, J.C., Petropolis, D.B., Manatakis, D.V., Maulana, T.I., Burchett, G., Schlünder, K., Witt, A., Shukla, A., Kodella, K., Ronxhi, J., Kulkarni, G., Hamilton, G.A., Seki, E., Lu, S., Karalis, K.C. (2021). Modeling alcohol-associated liver disease in a human Liver-Chip. Cell Rep 36, 109393.
Nawroth, J.C., Lucchesi, C., Cheng, D., Shukla, A., Ngyuen, J., Shroff, T., Varone, A., Karalis, K., Lee, H.-H., Alves, S., Hamilton G.A., Salmon M., Villenave R. (2020). A Microengineered Airway Lung Chip Models Key Features of Viral-induced Exacerbation of Asthma. Am J Respir Cell Mol Biol 63, 591–600
Nawroth, J.C., van der Does, A.M., Ryan (Firth), A., and Kanso, E. (2020). Multiscale mechanics of mucociliary clearance in the lung. Philosophical Transactions of the Royal Society B: Biological Sciences 375, 20190160.
Parekh, K.R., Nawroth, J.C., Pai, A., Busch, S.M., Senger, C.N., and Ryan, A.L. (2020). Stem cells and lung regeneration. American Journal of Physiology-Cell Physiology 319, C675–C693.
Nawroth, J.C., Barrile, R., Conegliano, D., van Riet, S., Hiemstra, P.S., and Villenave, R. (2018). Stem cell-based Lung-on-Chips: The best of both worlds? Adv. Drug Deliv. Rev.
Nawroth, J.C., Scudder, L.L., Halvorson, R.T., Tresback, J., Ferrier, J.P., Sheehy, S.P., Cho, A., Kannan, S., Sunyovszki, I., Goss, J.A., Parker, K.K. (2018). Automated fabrication of photopatterned gelatin hydrogels for organ-on-chips applications. Biofabrication 10, 025004.
Nawroth, J.C., Guo, H., Koch, E., Heath-Heckman, E.A.C., Hermanson, J.C., Ruby, E.G., Dabiri, J.O., Kanso, E., and McFall-Ngai, M. (2017). Motile cilia create fluid-mechanical microhabitats for the active recruitment of the host microbiome. PNAS 114, 9510–9516.
Benam, K.H., Novak, R., Nawroth, J.C., Hirano-Kobayashi, M., Ferrante, T.C., Choe, Y., Prantil-Baun, R., Weaver, J.C., Bahinski, A., Parker, K.K., Ingber, D.E. (2016). Matched-Comparative Modeling of Normal and Diseased Human Airway Responses Using a Microengineered Breathing Lung Chip. Cell Systems 3, 456-466.e4.
Nawroth, J.C., Lee, H., Feinberg, A.W., Ripplinger, C.M., McCain, M.L., Grosberg, A., Dabiri, J.O., and Parker, K.K. (2012). A tissue-engineered jellyfish with biomimetic propulsion. Nature Biotechnology 30, 792–797.