This book is devoted to innovative medicine, comprising the proceedings of the Uehara Memorial Foundation Symposium 2014. It remains extremely rare for the findings of basic research to be developed into clinical applications, and it takes a long time for the process to be achieved. The task of advancing the development of basic research into clinical reality lies with translational science, yet the field seems to struggle to find a way to move forward. To create innovative medical technology, many steps need to be taken: development and analysis of optimal animal models of human diseases, elucidation of genomic and epidemiological data, and establishment of “proof of concept”. There is also considerable demand for progress in drug research, new surgical procedures, and new clinical devices and equipment. While the original research target may be rare diseases, it is also important to apply those findings more broadly to common diseases. The book covers a wide range of topics and is organized into three complementary parts. The first part is basic research for innovative medicine, the second is translational research for innovative medicine, and the third is new technology for innovative medicine. This book helps to understand innovative medicine and to make progress in its realization.

This detailed book covers numerous expert methodologies to examine Hippo signaling on the structural, molecular, cellular, and organismal level. Beginning with a section on Drosophila genetics, the volume continues with parts exploring molecular and cell biological studies of the Hippo pathway, the use of structural biology and biochemistry, and a brief look at the Hippo pathway in mouse models. Written for the highly successful Methods in Molecular Biology series, chapters contain introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Comprehensive and practical, The Hippo Pathway: Methods and Protocols equips newcomers and specialists alike with key methodologies to accurately define the status of Hippo signaling in their experimental settings.

The Hippo pathway is a highly dynamic cellular signaling nexus that plays central roles in multiple cell types and regulates regeneration, metabolism, and development. The Hippo pathway integrates mechanotransduction, cell polarity, inflammation, and numerous types of paracrine signaling. If not tightly regulated, dysregulated Hippo pathway signaling drives the onset and progression of a range of diseases, including fibrosis and cancer. The molecular understanding of the Hippo pathway is rapidly evolving. This Special Issue contains ten articles contributed by established and up-and-coming Hippo pathway experts that, as a whole, provides an up-to-date overview of how dysregulated Hippo pathway activity is a common driver of specific diseases. The articles have a particular focus on the underlying molecular and cellular mechanisms that cause the Hippo pathway to go awry, and especially how this drives disease. The articles analyze disease-specific as well as common themes, which provides valuable insights into the fundamental molecular mechanisms in the dysfunctioning Hippo pathway, and thereby offer practical insights into potential future therapeutic intervention strategies.

​​The Hippo signaling pathway is rapidly gaining recognition as an important player in organ size control and tumorigenesis, and many leading scientists are showing increased interest in this growing field and it's relation to cancer. The chapters in this volume cover virtually all aspects of tumor biology, because members of the Hippo Pathway have been associated with numerous well-established cell signaling pathways, just to name a few; Ras, Wnt, TGFbeta and p53. Moreover, Hippo signaling is not solely involved in regulating “classic” tumor characteristics such as cell proliferation, survival and growth, but is also diversely involved in cell-autonomous and non-cell-autonomous differentiation, migration and organ size control. The primary audience are researchers interested in basic science in the areas of tumor suppression, cell cycle and size regulation, development and differentiation.

This volume provides the reader with an overview of the diverse functions of the RUNX family of genes. As highlighted in the introduction and several of the 29 chapters, humans and other mammals have three RUNX genes that are known to play specific roles in blood, bone and neuronal development. However, their evolutionary history has recently been traced back to unicellular organisms and their involvement in many well-known signaling pathways (Wnt, TGFb, Notch, Hippo) is indicative of a more general function in cell biology. Their documented roles in cell fate decisions include control of proliferation, differentiation, survival, senescence and autophagy. The pleiotropic effects of RUNX in development are mirrored in cancer, where RUNX genes can function as oncogenes that collaborate strongly with Myc family oncogenes or as tumour suppressor genes. In the latter role, they display hallmarks of both ‘gatekeepers’ that modulate p53 responses and ‘caretakers’ that protect the genome from DNA damage. Several chapters focus on the importance of these genes in leukemia research, where RUNX1 and CBFB are frequently affected by chromosomal translocations that generate fusion oncoproteins, while recent studies suggest wider roles for RUNX modulation in solid cancers. Moreover, RUNX genes are intimately involved in the development and regulation of the immune system, while emerging evidence suggests a role in innate immunity to infectious agents, including HIV. At the biochemical level, the RUNX family can serve as activators or repressors of transcription and as stable mediators of epigenetic memory through mitosis. Not surprisingly, RUNX activity is controlled at multiple levels, this includes miRNAs and a plethora of post-translational modifications. Several chapters highlight the interplay between the three mammalian RUNX genes, where cross-talk and partial functional redundancies are evident. Finally, structural analysis of the RUNX/CBFB interaction has led to the development of small molecule inhibitors that provide exciting new tools to decipher the roles of RUNX in development and as targets for therapy. This volume provides a compendium and reference source that will be of broad interest to cancer researchers, developmental biologists and immunologists.

Basic Science Methods for Clinical Researchers addresses the specific challenges faced by clinicians without a conventional science background. The aim of the book is to introduce the reader to core experimental methods commonly used to answer questions in basic science research and to outline their relative strengths and limitations in generating conclusive data. This book will be a vital companion for clinicians undertaking laboratory-based science. It will support clinicians in the pursuit of their academic interests and in making an original contribution to their chosen field. In doing so, it will facilitate the development of tomorrow's clinician scientists and future leaders in discovery science. - Serves as a helpful guide for clinical researchers who lack a conventional science background - Organized around research themes pertaining to key biological molecules, from genes, to proteins, cells, and model organisms - Features protocols, techniques for troubleshooting common problems, and an explanation of the advantages and limitations of a technique in generating conclusive data - Appendices provide resources for practical research methodology, including legal frameworks for using stem cells and animals in the laboratory, ethical considerations, and good laboratory practice (GLP)

1 Kevin Moses It is now 25 years since the study of the development of the compound eye in Drosophila really began with a classic paper (Ready et al. 1976). In 1864, August Weismann published a monograph on the development of Diptera and included some beautiful drawings of the developing imaginal discs (Weismann 1864). One of these is the first description of the third instar eye disc in which Weismann drew a vertical line separating a posterior domain that included a regular pattern of clustered cells from an anterior domain without such a pattern. Weismann suggested that these clusters were the precursors of the adult ommatidia and that the line marks the anterior edge of the eye. In his first suggestion he was absolutely correct - in his second he was wrong. The vertical line shown was not the anterior edge of the eye, but the anterior edge of a moving wave of patterning and cell type specification that 112 years later (1976) Ready, Hansen and Benzer would name the "morphogenetic furrow". While it is too late to hear from August Weismann, it is a particular pleasure to be able to include a chapter in this Volume from the first author of that 1976 paper: Don Ready! These past 25 years have seen an astonishing explosion in the study of the fly eye (see Fig.