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Mechanotransduction of cancer cell aggregates within the circulation

Primary Investigators:
Michael R. King
 
Brief Description of Project:
Mechanotransduction of cancer cells in the solid tumor environment is an active area of research, yet far less work has been done to examine the biological behavior of cancer cells in the blood flow environment. Recently, mechanical stimuli such as shear stress have received attention for their effects on cancer progression. For instance, studies have shown that shear stress has been associated with enhanced metastasis and cancer cell death. In the applicant’s laboratory, the synergistic effect of shear stress on tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced apoptosis of circulating tumor cells (CTCs) was demonstrated, as well as the unique ability of cancer cells to survive extremely high pulses of shear stress, comparable to blood cells. These mechanical cues can be translated into biochemical responses in cells through the process of mechanotransduction. It is proposed to subject cell suspensions to repeated shear stress pulses in a multiwell plate format to study shear stress response and to develop “mechanoresistant” cell lines that will be phenotypically and genotypically characterized with the goal of identifying the drivers that enable cancer cells to survive in circulation. Moreover, given that the presence of CTC aggregates in the blood signal more aggressive and metastatic disease, multicellular aggregates modeled after aggregates isolated and characterized from prostate cancer patient blood samples will be tested in vitro for their mechanical responses, and also used to guide the development of model cells and spheroids to be injected into experimental mouse models of bloodborne metastasis.

Desired Qualifications:
Experience with mammalian cell culture is preferred, but not essential. Familiarity with basic chemistry and biology laboratory procedures. Ability to collect, organize, and present data.
 
Nature of Supervision:
The PI will meet weekly with the researcher in a lab meeting, and additionally as necessary. The researcher will receive training and daily supervision from a senior PhD student in the lab.
 
A Brief Research Plan (period is for 10 weeks):
Weeks 1-2: training and observation
Weeks 3-8: experimentation and data collection, testing of different cell culture conditions on cellular shear stress responses.
Week 9: analysis of data and preparation of final report
Week 10: presentation of results.
 
Number of Open Slots: 1
 
Contact Information:
Name: Michael King
Department: Biomedical Engineering
Email: mike.king@vanderbilt.edu