Main Menu

Extracellular vesicles (EVs) are lipid bilayer-enclosed particles that are released from cells. EVs may contain proteins derived from their cells of origin with the potential as diagnostic biomarkers indicating the state of the cells when released. However, due to their small size (50-1000nm), the methods currently used to phenotype EVs have limited sensitivity and scale. A need exists for development of novel technologies improving EV detection and phenotyping.

Immunotherapy is a cutting-edge new category of treatment that aims to harness and, in some cases, modify the patient’s own immune cells to improve their ability to cure diseases. It can be an effective approach for a variety of conditions, ranging from cancer to inflammatory diseases.  However, a number of obstacles to the overall success of immunotherapy still exist.  For example, reactivity against a target antigen can be attenuated or the lifespan of the “modified” immune cells can be too short.

Multi-parameter flow cytometry has been extensively used in multiple disciplines of biological discoveries, including immunology and cancer research. However, the disadvantage of traditional flow cytometry platforms using excitation lasers and fluorescence detectors is spectral overlap when using multiple dyes on the same biological sample. Metaethical compensation of spectral overlap could only be effective to a certain degree. Mass cytometry is advantageous compared to flow cytometry but is pricey and requires highly skilled operators. 

Biological nanoparticles, like extracellular vesicles (EVs), possess unique biological characteristics making them attractive therapeutic agents, targets, or disease biomarkers. However, their use is hindered by the lack of tools available to accurately detect, sort, and analyze. Flow cytometers are used to sort and study individual cells. But, they are unable to detect and sort nanomaterials smaller than 200 nanometers with single epitope sensitivity.

Extracellular Vesicles (EVs), including exosomes and microvesicles, are nanometer-sized membranous vesicles that can carry different types of cargos, such as proteins, nucleic acids and metabolites. EVs are produced and released by most cell types. They act as biological mediators for intercellular communication via delivery of their cargos. This unique ability spurred translational research interest for targeted delivery of therapeutic molecules to treat a wide range of diseases. EVs also contain interesting information of their specific cellular origin.

Advanced colorectal carcinoma is currently incurable, and new therapies are urgently needed. Ephrin (Eph) receptors are a clinically relevant class of receptor tyrosine kinases. Related signaling pathways are associated with oncogenesis of a number of cancers. NCI investigators found that phosphotyrosine-dependent Eph receptor signaling sustains colorectal carcinoma cell survival, thereby uncovering a survival pathway active in colorectal carcinoma cells.

The Transforming Growth Factor Beta (TGF-ß) ligands (i.e., TGF-ß1, -ß2, -ß3) are key regulatory proteins in animal physiology. Disruption of normal TGF-ß signaling is associated with many diseases from cancer to fibrosis. In mice and humans, TGF-ß activates TGF-ß receptors (e.g., TGFBR1), which activates SMAD proteins that alter gene expression and contribute to tumorigenesis.  Reliable animal models are essential for the study of TGF-ß signaling.

Cytokines are a broad category of intercellular signaling proteins that are critical for intercellular communication in human health and disease. However, systematic profiling of cytokine signaling activities has remained challenging due to the short half-lives of cytokines, and the pleiotropic functions and redundancy of cytokine activities within specific cellular contexts.

The use of tumor transcriptomics for precision oncology has made significant advances, mainly by identifying cancer driver genes or actionable mutations for treatment with targeted therapies.  However, this strategy misses out on broader genetic interactions that could reveal additional biologically testable biomarkers for therapy response prediction and inform the selection of more effective drugs for targeted treatment.

The tumor microenvironment (TME) is a complex mixture of cell types whose interactions affect tumor growth and clinical outcome. Recent studies using fluorescence-activated cell sorting (FACS) and single-cell RNA sequencing (RNAseq) to elucidate tissue composition and cell-cell interactions in the TME led to improved biomarkers of patient response and new treatment opportunities. However, the use of FACS is limited to simultaneously measuring the expression of a few protein markers, whereas the use of single-cell RNAseq has been limited due to cost and scarcity of fresh tumor biopsies.