Understanding and targeting tumor cell adhesion and migration in cancer metastasis
Research in my 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 the contribution of these mechanisms to metastasis in cancer patients
C) Developing research and clinical tools to investigate metastatic behavior of tumor cells.
The laboratory currently pursues four integrated research objectives: 1) Defining how dynamic regulation of adhesion and migration controls metastasis, 2) Identification and characterization of the metastatic cell populations within a primary tumor, 3) Experimental modeling of metastasis in a clinically relevant manner, and 4) clinical implementation of molecular markers of migration as biomarkers of tumor progression and metastasis. Our mechanistic studies apply to much of the cancer spectrum but our clinical studies are focused on bladder and prostate cancer.
Specific mechanistic studies include an interrogation of the adhesion dynamics controlled by the tetraspanin CD151 and affiliated adhesion receptors (Integrins and IgG cell adhesion receptors). By tuning the adhesive properties of the cell, this mechanism can immobilize tumor cells or facilitate their dissemination. Dissecting the regulatory mechanism of CD151 demonstrates that the biphasic nature of migration is highly tunable through multiple epigenetic mechanisms. This dynamic regulation implies that escape from the primary tumor from is very much a non-linear aspect of metastasis that is less influenced by cancer genetics and more by the cellular context, interactions with adjacent tumor cells, the host and response to changing microenvironments.
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 optical imaging and computational strategies using fluorescent and luminescent proteins to visualize cell behavior intravitally along the metastatic cascade. In addition to visualizing the temporal and spatial dynamics of metastasis, we implement imaging and biochemical strategies to assess quantitatively how metastasis is impacted by specific mechanisms of motility.