New Grant to Develop Novel Disease Models of Colorectal Cancer

Goal to better understand disease development and metastasis

Cleveland Clinic researcher Emina Huang, MD, colorectal surgeon, Department of Colorectal Surgery, Digestive Disease & Surgery Institute, and staff member, Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, has been awarded a collaborative five-year, $2.6 million grant from the National Cancer Institute (NCI), part of the National Institutes of Health, to create innovative models of colorectal cancer that will enhance understanding of how the disease develops and spreads.

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This grant — a collaboration between Cleveland Clinic, Duke University and Cornell University — is the newest project funded by NCI’s Cancer Tissue Engineering Collaborative (TEC) Research Program. The program supports the development and characterization of state-of-the-art tissue engineered technologies for cancer research. With only four other TEC-funded research institutions nationwide, including Boston University, Harvard University, Brigham and Women’s Hospital and Massachusetts Institute of Technology, Cleveland Clinic is in great scientific company.

Leading-edge models of colorectal cancer

Dr. Huang and her team will work to develop three leading-edge models of colorectal cancer that will help researchers uncover the role inflammation, messenger RNA (transcriptome) and epigenetics play in the metastasis of colorectal cancer. What is unique about these models is that they will all use human tissues, both from the colon and other sites throughout the body. Studying colorectal cancer using cells from people, the population of ultimate interest, will maximize the applicability of findings and may speed the time of discovery.

This project is also innovative in that other conditions aside from colorectal cancer — including hypoxia and altered glucose levels — are reflected in these models. This will help mimic the extreme complexity of the colorectal cancer microenvironment. Additionally, the models are scalable and will allow for comparison between various cell types and combinations within and between the three models.

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A collaborative effort

While Dr. Huang is the principal investigator for the project, each collaborating organization will take the lead on developing one of the three models. Dr. Huang’s lab will develop an organotypic model. They will remove native cells from human colons, taken from resected colons and cancerous lesions, and repopulate them with new cells, including healthy cells as well as various types of cancer cells. Studying how the different classes of cells respond will help researchers understand the roles inflammation and cellular invasion and differentiation play in metastasis.

Bioengineers at Cornell University will develop the second model, which will utilize new body-on-a-chip technology. This technology will use human cells to create tiny, organ-like structures that mimic the function of a human colon. These structures will be placed on a chip and be connected to small fluid channels and sensors that will monitor activity in the artificial colon under experimental conditions.

Lastly, the team at Duke University will validate the two previously described models in an in vivo model, with the goal of better understanding how the immune system may play a role in colorectal cancer metastasis.

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Dr. Huang co-directs Lerner Research Institute’s Center of Excellence in Colon Cancer Metastasis Research. This program brings together top scientists with front-line physicians to speed the translation of lab discoveries into real benefits for patients. The center is currently working on several projects, including examining colon cancer’s cellular microenvironment, reversing the effects of angiogenesis, as well as understanding how genetic changes may make colon cancer cells more aggressive in some individuals and how those changes may be reversed. This project is the newest addition to the center’s impressive portfolio.

“I’m very excited to lead a project that brings together some of the top surgeons, researchers and biomedical engineers in their respective fields,” said Dr. Huang. “Colorectal cancer affects millions of adults in the United States. In some cases, the five-year survival rate is less than 13 percent. In order to develop effective treatment and prevention therapies for such a serious and complex disease, and deliver them to the patients and families who so desperately need them, we’ll need to work collaboratively across specialties and disciplines. With this new project, I think we’re well on our way.”