Research Program

Cancer Metastasis is the primary cause of cancer-related deaths. Research in the laboratory is dedicated to understanding the molecular biology of cancer metastasis and translating this knowledge to clinical application.

The research program is based on three central themes: A) Investigating the molecular mechanisms of tumor cell migration, B) Evaluating and validating these mechanisms in the patient population, and C) developing research and clinical tools to advance our studies.

The laboratory pursues three primary research objectives: 1) Characterization of the molecular mechanism of migration regulated by the tetraspanin CD151, 2) Identification and characterization of the metastatic cell population within a primary tumor, and 3) clinical implementation of molecular markers of migration as biomarkers of tumor progression and metastasis.

Specific mechanistic studies include:
The regulation of migration by tetraspanins: Among the molecular regulators of motility, we have found the tetraspanin CD151 to be a particularly critical component of metastasis. Interfering with its function through antibody binding inhibits extracellular matrix mediated migration and blocks >95% of the tumor cell dissemination in a spontaneous metastasis model. Using a newly-established in vivo motility assay, we have been able to demonstrate that altering the function of CD151 results in complete inhibition of in vivo motility for several tumor cell types. Ongoing studies try to determine the molecular mechanism by which this regulation of migration occurs.

Specific translational studies include:
Molecular mechanisms of migration contribute to metastasis and subsequently thought to be central to the cancer progression poor clinical outcome for cancer patients. We have developed a series of preclinical tests that determine the status of pro migratory mechanisms within the tumor. Using this technology it becomes possible to diagnose patients with aggressive disease, predict clinical outcome, and possible anticipate treatment response. Ongoing studies are expanding biomarker studies to a variety of cancers, including renal, bladder, prostate, lung, and breast cancer.

Specific technological advances:
We have developed novel intravital imaging strategies using the chick embryo to visualize cell behavior along the metastatic cascade in vivo. Quantitative analysis of metastasis have been implemented using species-specific PCR. Most recently we have developed a unique in vitro methodology called Magnetically Attachable Stencils (MAts) which make it possible to determine the contribution that the underlying matrix makes to cell migration. MAts are widely adapted in the VU community for the analysis of cell migration in vitro.

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