Pharmacology Of The Wnt Signaling System

This book reflects the state of the art of our understanding of the WNT signaling system, which comprises a network of signaling pathways initiated by the secreted WNT lipoglycoproteins, which are crucial for embryonal development, stem cell regulation, tissue homeostasis and repair. Dysfunction of this evolutionarily conserved signaling system leads to many diseases including developmental disorders, diverse forms of cancer, fibrosis, neurodegenerative disease and many more. The WNT signaling system is built upon 19 mammalian, secreted WNT lipoglycoproteins that interact with a plethora of distinct receptors, such as the G protein-coupled receptors called Frizzleds (FZD1-10), LDL receptor-like proteins (LRP5/6), receptor tyrosine kinases (ROR1, 2, RYK and PTK7). In addition, WNT pathways are tightly regulated by many secreted and cell-intrinsic negative regulators, such as soluble FZD-related proteins (SFRPs), Dickkopfs (DKKs), WNT-inhibitory proteins, TIKI, RNF43 and more. Understanding the basic mechanism in terms of receptor-ligand interaction, receptor selectivity, signal initiation and desensitization remain poorly understood, even though substantial advances have been made the recent years. Due to the involvement of the WNT signaling system in human disease, it appears obvious to target diverse branches pharmacologically and therapeutically. However, given the complexity of the system and its importance for stem cell regulation and tissue maintenance, therapy comes with obvious risks for severe side effects. The field is addressing the challenge to identify suitable targets and selective compounds for therapy allowing disease-selective therapeutic effects and balancing unwanted side effects. This book summarizes the current understanding of the basic and applied pharmacology in the WNT signaling system and bridges disciplines such as pharmacology, physiology, neurosciences, oncology and drug development.

The organizer area plays a central role in the formation of the embryonic axis and the central nervous system of all vertebrates including the human fetus. In The Vertebrate Organizer outstanding molecular development biologists and embryologists report their latest approaches in this fascinating research area using different vertebrate model organisms. The presented data are of central importance for the understanding of early human embryogenesis.

Macrophages are the sentinels of the immune system whose role has evolved beyond providing aseptic conditions to homeostasis, immune regulation, development, and behaviour. These cells have varied ontogenetic origins which reflects in their phenotypic and functional heterogeneity. Macrophage functions are fine-tuned by exogenous and endogenous signals and once tweaked, the information is included in their genetic makeup, albeit not indefinitely. Subversion of the macrophage functions is the hallmark of many pathogenic organisms and modulation of macrophage activity is pivotal to many therapeutic strategies. Fascinating and rapid developments in this field have necessitated the maintenance of currency of knowledge. This book provides a current account of information on varied topics in macrophage biology. Literature surveys have been presented in a captivating and lucid language. The contributing authors have also provided brief accounts of their own research. Every chapter provides a future perspective of what more could be achieved in the context of the current knowledge. The book will be of interest to students and researchers in microbiology, immunobiology, translational research, pathology, and related fields.

Wnt genes code for a family of secreted glycoproteins which fulfil important functions during the development of vertebrates and invertebrates. Wnts regulate as different aspects as differentiation, proliferation, cell migration, and cell polarity. Wnt proteins are able to activate different intracellular signaling cascades. This book describes different aspects of Wnt signaling during development of different species like the mouse, Xenopus, chicken, C. elegans or Drosophila and in different cellular contexts like heart formation or limb bud patterning. By doing such, this book provides, for the first time in printed form, an overview of the function of Wnt proteins during development. This book will be of interest to all professionals in the field of Wnt signaling, signal transduction or animal development.

There have been tremendous recent advances in the pharmacotherapy, dose regimens, and combinations used to treat cancer and for the treatment or prevention of the spread of disease. As a direct result of these advances, there are an increasing number of cancer survivors, although research dealing with chemotherapy-induced pain is still in its early

The greatest mystery of life is how a single fertilized egg develops into a fully functioning, sometimes conscious multicellular organism. Embryogenesis Explained offers a new theory of how embryos build themselves, and combines simple physics with the most recent biochemical and genetic breakthroughs, based on the authors' prediction and then discovery of differentiation waves. They explain their ideas in a form accessible to the lay person and a broad spectrum of scientists and engineers. The diverse subjects of development, genetics and evolution, and their physics, are brought together to explain this major, previously unanswered scientific question of our time. As a follow up on The Hierarchical Genome, this book is a shorter but conceptually expanded work for the reader who is interested in science. It is useful as a starting point for the curious layman or the scientist or professional encountering the problem of embryogenesis without the formal biology background. There is also material useful for the seasoned biologist caught up in the new rush of information about the role of mechanics in developmental biology and cellular level mechanics in medicine.

Most people have some interest in embryos; this probably results, in part, from their interest in understanding the biological origins of themselves and their offspring and, increasingly, concerns about how environmental change such as pollution might affect human development. Obviously, et- cal considerations preclude experimental studies of human embryos and, c- sequently, the developmental biologist has turned to other species to examine this process. Fortunately, the most significant conclusion to be drawn from the experimental embryology of the last two decades is the manner in which orthologous or closely related molecules are deployed to mediate similar - velopmental processes in both vertebrates and invertebrates. The molecular mechanisms regulating processes fundamental to most animals, such as axial patterning or axon guidance, are frequently conserved during evolution. (It is now widely believed that the differences between phyla and classes are the result of new genes, arising mostly by duplication and divergence of extant sequences, regulating the appearance of derived characters. ) Other vertebrates are obviously most likely to use the same devel- mental mechanisms as humans and, within the vertebrate subphylum, the - parent degree of conservation of developmental mechanism is considerable. It has long been recognized that particular vertebrate species offer either d- tinct advantages in investigating particular stages of development or are - pecially amenable to particular manipulations. No single animal can provide all the answers because not all types of experiments can be carried out on a single species.

Bridging the gap between basic scientific advances and the understanding of liver disease — the extensively revised new edition of the premier text in the field. The latest edition of The Liver: Biology and Pathobiology remains a definitive volume in the field of hepatology, relating advances in biomedical sciences and engineering to understanding of liver structure, function, and disease pathology and treatment. Contributions from leading researchers examine the cell biology of the liver, the pathobiology of liver disease, the liver’s growth, regeneration, metabolic functions, and more. Now in its sixth edition, this classic text has been exhaustively revised to reflect new discoveries in biology and their influence on diagnosing, managing, and preventing liver disease. Seventy new chapters — including substantial original sections on liver cancer and groundbreaking advances that will have significant impact on hepatology — provide comprehensive, fully up-to-date coverage of both the current state and future direction of hepatology. Topics include liver RNA structure and function, gene editing, single-cell and single-molecule genomic analyses, the molecular biology of hepatitis, drug interactions and engineered drug design, and liver disease mechanisms and therapies. Edited by globally-recognized experts in the field, this authoritative volume: Relates molecular physiology to understanding disease pathology and treatment Links the science and pathology of the liver to practical clinical applications Features 16 new “Horizons” chapters that explore new and emerging science and technology Includes plentiful full-color illustrations and figures The Liver: Biology and Pathobiology, Sixth Edition is an indispensable resource for practicing and trainee hepatologists, gastroenterologists, hepatobiliary and liver transplant surgeons, and researchers and scientists in areas including hepatology, cell and molecular biology, virology, and drug metabolism.