Interdisciplinary Initiatives Program Round 11 - 2022

Project Investigators:

Utkan Demirci, Radiology
Andrew Gentles, Medicine (Biomedical Informatics Research)

 

Additional Collaborators:

  • James D. Brooks, Urology
  • Lars Steinmetz, Genetics
  • Sharon Pitteri, Radiology
  • Demir Akin, Radiology

Abstract:

Liquid biopsies have gained attention for cancer detection and progression monitoring through biomarker identification in blood circulation due to the emergence of new and improved molecular analysis technologies. Extracellular vesicles (EVs) are nanometer-sized vesicles shed by cells to transport proteins, nucleic acids, metals, lipids, and metabolites, serving as essential components of bodily fluids. Circulating EVs in the blood carry cargo that reflects the properties of cell origin. Since cancer cells, with their rapid proliferation, are linked to differential expression of miRNAs and the associated oncogenic proteins, the mechanisms associated with the chain of events regulating proliferation like chromatin relaxation, miRNA expression, mRNA transcription, and protein synthesis, are also altered in cancer cells. The EVs released by cancer cells are expected to have high levels of oncogenic signaling cargo as compared to EVs released from normal cells. Moreover, sub-populations of EVs can be defined primarily by their size (ranging from 30 nm to 1 μm) or their density. As such, new techniques to isolate and fractionate these vesicles are needed. Common isolation strategies are based on density differences or affinity isolation, polymeric precipitation, chromatography, microfluidic devices, and size-based filtration. However, there are no existing tools that can seamlessly isolate EVs into their sub-populations based on size with a high yield that can allow downstream quantification. In this project, we will apply a state-of-the-art EV isolation technology combined with in vitro models, clinical samples, and downstream OMICs analyses as well as data analytics so as to create an EV atlas of prostate cancer. The goal is to develop EVs as surrogate non-/minimally-invasive biomarkers as a new form of early detection diagnostic modality that can be used to understand the underlying biology of solid organ tumors. Upon successful conclusion of the proposed studies, we will identify key EV parameters, such as their subtypes and cargo, that could have a significant impact on public health.