A Patient-Specific in silico Model of Inflammation and Healing Tested in Acute Vocal Fold Injury

The development of personalized medicine is a primary objective of the medical community and increasingly also of funding and registration agencies. Modeling is generally perceived as a key enabling tool to target this goal. Agent-Based Models (ABMs) have previously been used to simulate inflammation at various scales up to the whole-organism level. We extended this approach to the case of a novel, patient-specific ABM that we generated for vocal fold inflammation, with the ultimate goal of identifying individually optimized treatments. ABM simulations reproduced trajectories of inflammatory mediators in laryngeal secretions of individuals subjected to experimental phonotrauma up to 4 hrs post-injury, and predicted the levels of inflammatory mediators 24 hrs post-injury. Subject-specific simulations also predicted different outcomes from behavioral treatment regimens to which subjects had not been exposed. We propose that this translational application of computational modeling could be used to design patient-specific therapies for the larynx, and will serve as a paradigm for future extension to other clinical domains

Developmental biology of melanocytes

Apart from embryonic stem cells (ESCs) in the blastocyst, neural crest stem cells (NCSCs) in vertebrate embryos represent the stem cell population in our body with the broadest developmental potential, generating most of the neurons and glia of the peripheral nervous system (PNS) as well as various nonneural cell types, such as smooth muscle cells in the outflow tract of the heart, craniofacial bone, and cartilage and, in particular, melanocytes in the skin. It is assumed that a third of all congenital birth defects are due to failures in neural crest development, illustrating the significance of this stem cell population. Moreover, processes underlying melanocyte development appear to be recapitulated, at least partially, during formation of melanoma, the most aggressive skin tumor. For instance, it has recently been shown that an embryonic NCSC gene expression signature is reactivated upon tumor initiation in a zebrafish model of melanoma, suggesting a functional involvement of a NCSC program in tumors originating from neural crest derivatives. Thus, to gain insights into melanoma biology, it is important to understand the mechanisms regulating NCSC and melanocyte development, as outlined in this chapter