Rui Wang
Case Western Reserve University, OH·Pharmacology
Colorectal cancer becomes far more deadly once it spreads. More than 80% of these metastases form in the liver.
- Fields
Pharmacology
Medicine & Clinical Research
Biology
- Topics
colorectal cancer
liver metastasis
receptor tyrosine kinase
- Grants
- 1 known grant, through Jan 2029
What they work on
- Determine whether LRG1 secreted by liver endothelial cells drives colorectal cancer liver metastases to start and grow, using mice lacking endothelial LRG1 and an LRG1-neutralizing antibody.
- Test LRG1's role in clinically relevant models of metastatic colorectal cancer, including patient-derived xenografts and organoids.
- Determine how LRG1 binds and activates HER3, a growth-factor receptor on cancer cells, as a new partner molecule distinct from neuregulins.
- Assess whether HER3 activation in tumors relates to outcomes for patients with metastatic colorectal cancer, as a potential prognostic biomarker.
More about the research
The liver is unusually rich in endothelial cells, the cells that line blood vessels. The team found that liver endothelial cells release soluble factors that help colorectal tumors grow nearby. This is separate from their familiar role in building blood vessels. A key relay for this signal is HER3, a growth-factor receptor on cancer cells. But the endothelial cells switched HER3 on without neuregulins, the only known molecules that activate it. The team then found that LRG1, a protein secreted by liver endothelial cells, binds and activates HER3 and drives colorectal cancer cell growth. Blocking LRG1 throughout the body slowed tumor growth and extended survival in mice.
Why it matters
Patients with colorectal cancer that has spread to the liver have much worse outcomes than those with localized tumors. This work could identify HER3 activation as a marker for predicting how patients will fare. It could also establish LRG1 and other parts of the LRG1-HER3 pathway as potential targets for new therapies.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Yekaterina Zaytseva
University of Kentucky, KY·Medicine & Clinical Research
Determine whether FASN overproduction in colorectal cancer cells, through the exosomes they release, turns liver hepatic stellate cells into tumor-supporting fibroblasts, using genetic changes and the FASN inhibitor TVB-2640.
Christopher LaRocca
University of Minnesota, MN·Medicine & Clinical Research·Early-career
Identify which viral fiber structure, the part that attaches the virus to a cell, and which promoter, the genetic switch driving replication, give the strongest and most selective infection of human colorectal cancer cells, using cancer cell lines and patient-derived tissue slices.
Shiaowen Hsu
Duke University, NC·Medicine & Clinical Research
Test whether minimal residual disease cells from colorectal cancer patients that resist standard-of-care chemotherapy are more likely to metastasize and cause recurrence, using MicroOrganoSpheres grown from portal venous blood collected during surgery.
The school
Case Western Reserve University: 34 labs on PI Pages, $643M a year on research, 213 research doctorates a year.
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