Core E The discovery, characterization and development of novel therapeutic strategies to ameliorate the morbidity and mortality of graft-versus-host disease (GVHD) requires an interdisciplinary approach leveraging emerging biological insights and novel pharmacologic strategies. Already, this Program has successfully developed new and effective therapeutic interventions based on biological hypotheses tested in preclinical models of GVHD. To accelerate the pace of research and to more immediately connect the preclinical and clinical programs, we have created a new Experimental Therapeutics Core Laboratory. The goals of the Core are (a) to provide immediate and unrestricted access to chemical probes, investigational agents and therapeutic substances for preclinical and biological assessment, (b) to derive chemical derivatives of active agents to address disclosed pharmacologic liabilities encountered in this research, as needed, (c) to provide high-purity synthetic peptides allowing the validation of surface antigens and (d) to purify recombinant proteins or protein domains for the characterization of putative alloreactive antibodies. Beyond these technical objectives, the leadership and staff of the Experimental Therapeutics Core Laboratory will provide expertise in molecular pharmacology guiding selection and use of chemical tools alone or in combination in biological and translational studies proposed herein. As therapeutic agents enter human clinical investigation, the Core will contribute to the selection and assessment of clinical biomarkers of drug action. The completion of these objectives will require the development of new methods in organic synthesis, parallel solid-phase peptide synthesis, analytical chemistry, protein production and mass spectrometry. As such, the Core is located in a state-of-the-art chemical biology laboratory which possesses the infrastructure, expertise and technology required to complete the stated Aims and to integrate inter-programmatic activities.
Core E The discovery of new treatment strategies for graft-versus-host disease requires the interdisciplinary study of emerging drug molecules in translational and mechanistic models. The discovery of new alloreactive antigens underlying this morbid and often fatal condition requires highly purified proteins and peptides to test as immunogens. The new Experimental Therapeutics Core will connect numerous activities in the Program by providing immediate access to synthesized investigational agents, peptides and proteins, while advising on their use in biological and clinical studies.
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