Project title: Generation and characterization of a novel genetically modified patient–derived NET organoid system

Project Description:

The slow growth of NETs makes their in-vitro propagations very challenging and many experimental approaches impractical. The paucity of clinically relevant models has limited progress in the field. Dr. Yao and his team will develop a new NET model system that will enable them to turn on growth to induce enough NET cell growth to conduct experiments. Importantly, this model will also allow them to subsequently turn off a growth switch to return the NET cells to their original biology for use in broad drug screening trials to identify the drugs or drug combinations that may most effectively destroy NETs.

What critical NET problem will you try to solve through your research?

The diagnosed incidence of NETs continues to rise. While slow growing, NETs are lethal when advanced. Development of effective therapy has been limited by a lack of clinically relevant laboratory models that can enable screening of new treatments. In this project, Dr. Yao and his team will generate a biobank of intestinal and pancreatic NET models to represent the spectrum of diversity in human NET behavior.

Why is this important?

The very slow-growing nature of well-differentiated NETs makes it difficult to develop NET models in laboratories. On average, human NETs take 5-18 months to grow even 20%. Under such conditions, it is very difficult to keep NET cells alive in the laboratory, and even if possible, it may take years to conduct even a single experiment.

What will you do as part of this research project?

We propose a novel approach by genetically modifying human-derived NET cells to insert a growth switch that can be controlled by doxycycline, a common antibiotic. This will enable us to “turn on” the growth switch to induce NET cells to grow to a sufficient amount to conduct experiments and subsequently “turn off” the growth switch to return the NET cells to normal biology.

How might your research improve the diagnosis and/or treatment of NETs? 

Successful execution of the project will help us to create a bank of pancreatic and intestinal NET models to represent the spectrum of diversity in human NET behavior. This will let us test promising new therapies quickly in the lab. 

What is your next step?

We will generate a library of human NET models and genetically and molecularly characterize these models to ensure our models are useful in studying human NETs and testing new treatments. 

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