Jonathan W. Boyd
Department of Orthopaedics and Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, WV, USA

Marc Birringer
Department of Oecotrophologie, Fulda University of Applied Sciences, Fulda, Hesse, Germany

Meghan Cromie
National Jewish Health, Denver, CO, USA

Patricia E. Ganey
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA

Weimin Gao
Department of Occupational and Environmental Health Sciences, West Virginia University School of Public Health, Morgantown, WV, USA

Alice Han
Chem Bio & Exposure Sci Team, Pacific Northwest National Laboratory, Richland, WA, USA

Carlo Laudanna
Department of Pathology and Diagnostics, University of Verona, Verona, Italy

Zhongwei Liu
Department of Occupational and Environmental Health Sciences, West Virginia University School of Public Health, Morgantown, WA, USA

Julie Vrana Miller
Cardno ChemRisk, Pittsburgh, PA, USA

Sean A. Misek
Department of Physiology, Michigan State University, East Lansing, MI, USA

John Morris
Resource for Biocomputing, Visualization and Informatics, University of California, San Francisco, CA, USA

Julia A. Mouch
Department of Orthopaedics, West Virginia University School of Medicine, Morgantown, WV, USA

Richard R. Neubig
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA

Robert H. Newman
Department of Biology, North Carolina A&T State University, Greensboro, NC, USA

Sakshi Pratap
Birla Institute of Technology & Science, Goa, India

Maren Prediger
Institute for Microproductions, Leibniz University, Hannover, Germany

Nicole Prince
Department of Orthopaedics, West Virginia University School of Medicine, Morgantown, WV, USA

Giovanni Scardoni
Center for Biomedical Computing, University of Verona, Verona, Italy

Song Tang
National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing, China

Gabriele Tosadori
Center for Biomedical Computing, University of Verona, Verona, Italy

Qian Wang
Department of Respiratory Medicine, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China

Jonathan Boyd is the associate director of the Musculoskeletal Laboratory and an associate professor of orthopaedics at the West Virginia University School of Medicine (WVUSOM). He holds additional joint appointments in the Department of Physiology and Pharmacology (WVUSOM) and the Department of Occupational and Environmental Health Sciences (WVU School of Public Health). Dr. Boyd also holds appointments as a guest professor at Fulda University (Germany) and a guest researcher at the Centers for Disease Control and Prevention at the National Institute for Occupational Safety and Health (CDC/NIOSH). He received his BS Biochemistry from the University of Texas at Austin in 1998 and his PhD Environmental Toxicology from Texas Tech University in 2004. His expertise is in mechanistic toxicology, mammalian signal transduction, and musculoskeletal trauma. Dr. Boyd's research uses fundamental thermodynamic principles to investigate the pharmacodynamic responses of living systems. In general, he is interested in understanding the mammalian response to both chemical and physical stressors, and specifically, he is working toward an understanding of how humans integrate (from cellular mechanisms to physiological integration) chemical and biochemical signals in response to stimuli. His research involves multiple hierarchical levels of biological samples that include mammalian cell culture, animal models, and human subjects coupled with analytical techniques that range from single‐point detectors to multidimensional imaging. The applications of his work range from toxicity screening to surgical diagnostics, and he has published over 40 papers, technical reports, and book chapters associated with his research. Finally, Jonathan is married to the love of his life, Naomi, and together they have the three best children on Earth, Jack, Lucy, and Gwen, who all fill his life with pure joy.

Richard (Rick) Neubig is professor and chair of Pharmacology & Toxicology at Michigan State University associated with the three medical colleges. Dr. Neubig received his BS in Chemistry from the University of Michigan in 1975, his MD from Harvard Medical School in the Harvard‐MIT Program in Health Sciences and Technology in 1981, and his PhD in Pharmacology from Harvard University in 1981. He trained in internal medicine at the University of Michigan Hospitals and then joined the faculty in the Departments of Pharmacology and Internal Medicine in 1984. He moved to Michigan State University in 2013 to take the position of chair of Pharmacology & Toxicology. His research has primarily focused on G‐protein‐coupled receptor (GPCR) signaling. His early work in the 1980s and 1990s primarily used ligand binding kinetics and biochemical studies to decipher receptor/G‐protein interactions. In the mid‐1990s his work took a turn to translational research and academic drug discovery. He helped establish high‐throughput screening and drug discovery centers at both the University of Michigan and Michigan State University. His current work relates to therapeutic discovery in cancer, scleroderma, and other fibrotic diseases as well as mechanisms and therapeutics of genetic epilepsies. He was president of the American Society for Pharmacology and Experimental Therapeutics (ASPET) (2012–2015), and he received the Astellas and ASPET‐Pharmacia awards for translational pharmacology from that organization. He served on the IUPHAR Receptor Nomenclature Committee from 2000 to 2015 and was GPCR co‐chair. He was named Fellow of the American Association for the Advancement of Science (AAAS) in 2015 and is currently chair of Section S, Pharmaceutical Sciences, of the AAAS. He loves nature and the outdoors, a passion that he shares with his amazing wife, Laura Liebler. They are the lucky parents of two wonderful children, Graham and Maia, who have brought them equally wonderful spouses and a totally awesome granddaughter, Enna.

“All the world's a stage, and all the men and women are merely players; they have their exits and their entrances, and one man in his time plays many parts....” This famous phrase was penned by William Shakespeare in As You Like It, and he followed it with a description of what he called the seven ages, or phases, of life. While he was referring to the process of aging via a metaphor of actors playing roles in this grand production that is our existence, I often think of both the phases and roles that genes and proteins play as they enter and exit their stages of development. From an infancy represented by a group of linked nucleotides blissfully unaware of their surroundings through an awakening of transcription that is followed by the trials and tribulations of proper editing and posttranslational modifications, the next phase is a productive and functioning role in a new environment that is interacting with many other actors who are also playing their roles. However, unbeknownst to the protein, this phase of role‐playing usually begins to signal the end, when all activity will decrease and virility of function will cease. Ultimately, the once‐powerful protein loses its ability to interact with partners, and now without the capacity to sense and respond its surroundings, it is devolved via catabolism back into the elements of its infancy, again unaware of what the future might bring.

As pharmacologists and toxicologists today, we focus on the biological response of adding and removing actors, both heroes and villains, to the mixture of concurrent scenes that are happening on several different stages within the body (i.e. organ systems). Further, these actors are joining these ongoing scenes during different acts (i.e. phases), which greatly affects the role that existing genes and proteins may be playing now or in the future. Our goal is to understand how these new cast additions (or removals) might impact the overall production, and therefore we must dive into and dissect each potential role, or interaction, as it pertains to the overall structure and phases that are necessary for life. One means to achieve this is via monitoring alterations in cellular signal transduction cascades that are responsible for both functional interactions (roles) and the transitions between phases (or acts).

The pharmacodynamic response of cells to xenobiotics is primarily coordinated by signal transduction networks. Signal transduction proteins are embedded in early response networks that use positive and negative feedback to generate extremely diverse functions like amplification and perfect adaptation, reversible and irreversible switches, homeostasis, and oscillations. Irregular signal transduction activity has been associated with many major human diseases, including several forms of cancer, age‐related diseases, and diabetes, to name a few.

From a pharmacological perspective, proteins involved in signal transduction have become one of the most intensively pursued drug targets to date for several reasons, including their direct association with a wide variety of cellular functions (both proliferation and apoptosis), and previous success for the treatment of disease (chronic myeloid leukemia). Depending on the pharmacological effect, agonists/activators or antagonists/inhibitors can be used to harness the therapeutic benefits. The steroid hormone receptors, such as the estrogen receptor, androgen receptor, and glucocorticoid receptor, are among the best examples, because both the steroid receptor agonists and antagonists have been successful clinical drugs.

From a toxicological perspective, modern evaluations have evolved to consider toxicity as a perturbation of biological pathways or networks. As such, toxicity testing approaches are shifting from common endpoint evaluations to pathway‐centered approaches based on signal transduction networks, where the degree of perturbation of select networks is monitored. These new approaches are greatly increasing the information available to toxicologists, but signal transduction in toxicological research is in its infancy. Therefore, toxicologists need a resource that will guide their future study design and interpretation.

The goal of this book is to provide a comprehensive understanding of signal transduction research that is applicable to industry, academia, and government written for an audience with a background in biochemistry or cell biology. The primary aim of this book is to give the reader a solid background in signal transduction networks while supplying the tools necessary for further research in this expanding area. These tools include a discussion of experimental design, sample handling, analytical measurement techniques, data analysis, and interpretation (including novel modeling approaches). Finally, this book is organized hierarchically so that the first four chapters describe the architecture of signaling networks, from a physical basis of understanding signaling through mechanisms, physiological response, and human disease. The last half of the book is a “how‐to” for incorporating signal transduction research into your portfolio with several examples, from designing signal transduction studies to measuring and monitoring signaling responses, interpreting and transforming data into usable information, an application in a toxicological study, and finally outlining critical future needs in signal transduction research.