| Description | Bridging the Gap Between the Petri Dish and the Patient: Integrative Approaches to Put Disease in Context
Abstract:
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 protein matrices for studying physiologically relevant cancer cell migration behaviors. We have identified specific matrix features that induce conserved transcriptional and migratory modules in multiple solid tumor cell types. We have demonstrated at the RNA and protein level that this in vitro genotype-phenotype is linked to a clinically observed phenotype called vasculogenic mimicry (VM), which 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. Bio:
Dr. Stephanie Fraley joined UC San Diego in July 2014 as an assistant professor of Bioengineering. Her research takes a multidisciplinary and multi-scale approach to (1) understand mechanisms of cell migration underlying human disease, in particular cancer, and (2) develop clinical profiling technologies for improved understanding and treatment of human diseases. She earned her B.S. in Chemical Engineering in 2006 from The University of Tennessee Chattanooga and her Ph.D. in Chemical and Biomolecular Engineering in 2011 from The Johns Hopkins University. For her graduate work, she was awarded an NSF Graduate Research Fellowship, National Tau Beta Pi Fellowship, and was an Achievement Rewards for College Scientists Scholar, Johns Hopkins Heath Fellowship, National Siebel Scholarship, and ASEE/NSF Engineering Innovations Fellowship. Dr. Fraley then joined the Emergency Medicine department at The Johns Hopkins University as a postdoctoral fellow where she developed novel technological approaches to sensitively detect and quantitatively identify genetic material circulating in the bloodstream. Recently, she received a National Burroughs Wellcome Fund Career Award at the Scientific Interface for her research merging clinical diagnostic and basic research approaches. She is also a SAGE Bionetworks Scholar, Kavli Frontiers of Science Fellow, BMES CMB Rising Star awardee, and recipient of an NSF CAREER award. Molecular Engineering and Sciences Seminar Series This weekly seminar brings together students, faculty and invited guests from various disciplines across campus to explore current trends in molecular engineering and nanotechnology. It is a forum for active interdisciplinary discussions. These talks are open to the public and attract a diverse audience of students and faculty. |
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