Disrupting the Metastatic Niche to Improve Patient Outcomes
|Interdisciplinary Areas:||Engineering-Medicine, Others
The majority of breast cancer related deaths occur as a result of metastasis. Once the cancer cells metastasize, the 5-year relative survival rate for breast cancer patients drastically drops. During metastasis, a complex series of events is initiated by changes in the extracellular matrix (ECM) composition and architecture in distant tissues, where the metastatic cancer cells take root and form secondary tumors. These distinct changes in the premetastatic niche (PMN) facilitate tumor cell colonization, phenotypic heterogeneity of the cell population, and contribute to drug resistance frequently observed in metastatic tumors. Using an engineered model of the PMN, we have demonstrated that extracellular vesicles (EVs) facilitate dynamic changes in premetastatic tissues, and that blocking key events during PMN formation disrupts the metastasis. Fundamental gaps remain in identifying critical events within the niche that facilitate metastatic colonization of tumor cells, cellular plasticity, and drug resistance. By targeting these events, metastasis can be disrupted, eliminating the most lethal aspect of breast cancer. The overall goal of this proposal is to develop treatment strategies designed to effectively target the premetastatic niche, disrupting critical ECM changes that make the distant tissues hospitable to metastatic cancer cells.
The ideal candidates will be creative, curious, collaborative and highly motivated. Experience in proteomics, tissue culture, cell-based assays, basic molecular biology techniques (such as protein extraction and quantification), and confocal microscopy are highly desired. Other skills include the development and discovery of new methodologies and validation of the existing approaches for cancer therapy. Experience with executing in vivo studies involving the handling, care and use of laboratory animals and surgical procedures related to tumor inoculation and therapy are desirable.
Luis Solorio, firstname.lastname@example.org, Weldon School of Biomedical Engineering, https://soloriolab.wixsite.com/tmet
Mike Wendt, email@example.com, Medicinal Chemistry and Molecular Pharmacology,
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