We uses a systems and mathematical modelling approach (Tanaka & Ono
2013) to elucidate the regulatory mechanisms of skin barrier homeostasis
and the pathogenesis of atopic dermatitis (AD, a common chronic skin disease)
that occurs as a result of the dynamic interplay between environmental
triggers, immune dysregulation and skin barrier defects (Domínguez-Hüttinger
et al. 2016). Our research aims to develop computational tools for a clinical
decision support system that integrates and analyses clinical data to design
personalised treatment strategies for atopic dermatitis (AD).
We developed a mechanistic model of AD pathogenesis (Domínguez-Hüttinger et al. 2016) and elucidated the “double switch” motif coherently explains the mechanisms of the onset and dynamic progression of AD. We have also proposed a mathematical method to quantify and visualise the depth-dependent barrier function by “resistance profiles” (van Logtestijn et al. 2015), obtained by integrating non-invasively obtained data on TEWL and water concentration profiles measured by confocal Raman microspectroscopy. Our mathematical method complements experiments in gaining quantitative understanding of intricate biological mechanisms, and allows us to conduct in silico simulations to predict the spatial-temporal dynamics.
We further apply control theoretical methods to design optimal treatment regimens for individual patients (Christodoulides et al. 2017), and machine learning methods to develop data-driven models to complement our mechanistic model.
E. Domínguez-Hüttinger, P. Christodoulides, K. Miyauchi, A.D. Irvine, M. Okada-Hatakeyama, M. Kubo, and R.J. Tanaka.
Journal of Allergy and Clinical Immunology, 139:6, 1861–1872, 2017
P. Christodoulides, Y. Hirata, E. Domínguez-Hüttinger, S.G. Danby, M.J. Cork, H.C. Williams, K. Aihara, R.J. Tanaka.
Philosophical Transactions of the Royal Society A 375:20160285, 2017
M. Yokouchi, T. Atsugi, M. van Logtestijn, R. J. Tanaka, M. Kajimura, M. Suematsu, M. Furuse, M. Amagai, and A. Kubo.
eLife, 5:e19593, 2016
M. D. A. van Logtestijn, P. J. Caspers, S. Kezic, D. R. Hoffman, D. W. Koenig, M. Ono, G. N. Stamatas and R. J. Tanaka.
R. J. Tanaka and M. Ono.