Protein Phosphorylation Networks in Health and Disease

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Summary Kinases regulate normal physiological response to environmental perturbations. When dysregulated, either through aberrant expression or mutation, protein kinases have been implicated in a host of diseases, from developmental disorders to cancer. Accordingly, many of the successful targeted therapeutics for cancer and developmental diseases have been generated against aberrantly activated kinases. Unfortunately, the therapeutic efficacy of most of these agents has been largely disappointing due to the emergence of resistance caused in part by rewiring of the signaling networks and by mutations that interfere with drug binding. In many cases, mutant kinases cannot be efficiently inhibited due to our incomplete understanding of the effect that disease mutations exert on kinase activation state, downstream network compensation, and anticipated response to a drug. Understanding the normal physiological role of protein kinases and their phosphorylation networks will significantly improve our ability to selectively target disease-associated kinases and will enable the development of next-generation targeted combinatorial therapeutics with greatly increased efficacy. There are three specific objectives of the FASEB 2023 Protein Phosphorylation Networks in Health and Disease Conference. The first objective is to describe the state of the art in kinase structure, function, localization, regulation, interactions, and targeting in both normal and pathological cell states. To accomplish this goal, we have planned a series of keynote and plenary speakers from many of the leading experts in the field, multiple short talks selected from the poster abstracts, poster sessions, several focused workshops, and informal discussions. Since the challenges in this field are daunting and will require collaborative efforts to solve them, the second goal is to enhance interactions between academia, industry, and clinical science and to enhance interactions between research approaches, from biochemical-, structural-, systems-level, and computational fields related to phosphorylation. To this end, we have specifically invited speakers representing each of these topics, and are planning workshops on new techniques in the field. The third objective is to invest intellectually and financially in the future by supporting promising young trainees, with an eye towards increasing diversity in the field. The goal is to encourage trainees to be successful and stay in the field by providing intellectual support through discussions with senior scientists, poster sessions, opportunities to speak, awards that recognize their achievements, and by providing financial support with competitive travel awards. The expected outcomes are increased collaborations, retention of young scientists in the field, identification of new developmental processes and diseases linked to kinase signaling, and exploration of new state of the art approaches for identifying and developing therapeutic targets and strategies to combat cancer, developmental deficiencies, and other diseases.