Bridging the Gap Between the Petri Dish and the Patient: Integrative Approaches to Put Disease in Context
Seminar | March 14 | 12-1 p.m. | 106 Stanley Hall
Stephanie Fraley, University of California, San Diego
Technological advances continue to accentuate the fact that biological knowledge is highly context and time dependent. It is now clear that in vitro model systems, which are necessary for studying the molecular mechanisms of disease, fail to represent many critical pathophysiological features of human disease. Thus, findings from in vitro studies rarely translate directly into impact for patients. A major challenge remains the development of a scientific framework capable of capturing critical disease features in a dish and bridging knowledge flow between in vitro and clinical understanding of human disease. In particular, diseases that involve complex microenvironmental deregulation, like cancer, are needed. This will require innovation in identifying, characterizing, and recapitulating key aspects of three-dimensional (3D) tissue architectures to study dynamic cell-microenvironment relationships. My lab is developing and validating strategies on both the in vitro and clinical side of this problem to bridge the knowledge gap with the goal of significantly increasing the translation rate of basic science studies.
From the in vitro perspective, I will present our work engineering 3D culture systems to replicate and study physiologically relevant cancer cell migration behaviors. We have identified specific 3D matrix features that induce conserved transcriptional and migratory responses in multiple solid tumor cell types. Using publicly available databases of human samples and data, we have demonstrated that this in vitro genotype-phenotype is linked to a clinical phenotype called vasculogenic mimicry (VM). VM is correlated with advanced metastatic disease in over 16 cancers but poorly understood. Our in vitro studies are revealing key aspects of the VM induction mechanism, which we are validating in vivo with the goal of identifying therapeutic targets.
From the clinical perspective, I will present our work developing highly sensitive molecular detection technologies to enable quantitative, rapid, and inexpensive genotyping in clinical blood samples. By integrating high resolution melting of nucleic acids, universal PCR, machine learning, and digitizing microfluidics, our technology is poised to overcome current diagnostic limitations enabling single molecule sensitive profiling of circulating DNA/RNA. We apply this to microRNA, gene methylation, and infectious disease profiling.