The Proteogenomics Research Institute for Systems Medicine (PRISM) is a non-profit research institute in the San Diego biotechnology hub that employs a unique model to accelerate the rate at which new discoveries move from “bench to bedside.” PRISM was founded in 2009 by Jan E Schnitzer, MD, a world-renowned expert in vascular biology with more than 30 years of research experience, and currently has nearly 30 employees, including primary investigators, scientists, visiting clinicians in training, post-doctoral fellows, graduate students, research technicians, and support staff. PRISM is based on a new fundamental concept of “proteogenomic imaging.” PRISM is unique because this approach seamlessly integrates target discovery efforts with therapeutic and imaging agent development followed by extensive preclinical and clinical validation, as depicted below:
Humans have approximately 21,000 genes which can generate several hundred thousand possible proteins targets because of extensive RNA processing, post-translational modification, and the formation of functional protein complexes. Thus, it may not be surprising that genomic and proteomic analysis of tissue and cell samples from normal and diseased states have already yielded thousands of genes and gene products as candidate disease biomarkers and therapeutic targets. Yet the shear number of candidates can overwhelm the required but time-consuming in vivo validation process. The dilemma in target discovery today has become identifying the few targets that are utile in targeting, imaging, and treating disease. Clearly, new analytical strategies are required to reduce data complexity and to focus the power of global proteomics and genomics to permit rapid discovery and validation of tissue- and disease-specific molecules in vivo.
By combining the power of high-throughput proteomics and genomics expression mapping strategies with a wide variety of imaging techniques and by developing and applying these technologies to interrogate native tissue conditions in the body (“the in vivo context”), PRISM can rapidly identify and validate new disease targets and biomarkers and move new diagnostics and therapies into clinical trials. This unique strategy requires the assembly, integration, and synergistic interaction of a team of scientists with diverse expertise in tumor biology, chemistry, bioinformatics, genetics, proteomics, histology, physiology, pathology, computer science, nanotechnology, imaging science, and oncology.
Discovery Engine
The primary discovery engine is driven by the power of new “proteogenomics” technologies to define key expression profiles in normal and diseased cells and tissues. Comparative and subtractive profiling is accomplished through proteogenomic mapping and tissue array analysis to identify proteins and genes that are unique to single tissue or disease states. PRISM has developed, and will continue to develop and optimize new and unique technologies required to enable each critical step in this discovery process. This integrated course of action yields new disease biomarkers and even target candidates with diagnostic, prognostic and therapeutic applications.
Agent Generation & Preclinical Validation
High-quality affinity probes are necessary to determine tissue- or disease specific expression of new potential targets or biomarkers and to develop new agents that can diagnose, image and treat human disease. PRISM has developed and optimized new techniques to create monoclonal antibodies and other affinity probes. The assessment of biomarker expression and target utility requires in vivo imaging. PRISM has a state-of-the-art imaging facility to visualize disease processes at the level of the whole animal to the subcellular level. New techniques at PRISM facilitate dynamic live imaging that can follow disease progression at the cellular level. The preclinical output includes key insights into target expression and mechanisms of action, fundamental understanding of where probes go and how effectively they target diseased tissue, and basic information not only on how effective a new targeted therapy can be but also on how it works in the context of the whole body. Perhaps the most important output from the preclinical validation studies has been, and will continue to be, the advancement of new imaging and therapeutic agents for clinical testing in human patients. To facilitate this, PRISM has continued to develop better animal models that duplicate human disease and more accurately predict clinical therapeutic outcomes. PRISM has also developed novel molecular and functional probes that can noninvasively image pathophysiological events specific to a single tissue even in humans.
Clinical Trials
After toxicology testing and GMP production of the new imaging and/or therapeutic agents, we collaborate with clinical partners to begin Phase 0 and Phase 1 trials. We have a growing network of clinical partners affiliated with major national and international clinical trial centers. This external network affords us many opportunities to pick the most enthusiastic and competent partner for each new clinical trial.