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Leukocytes as Mobile Carriers of Anti-Cancer Proteins to Neutralize Circulating Tumor Cells for the Prevention of Cancer Metastasis

Primary Investigators:
Michael R. King
 
Brief Description of Project:
More than 90% of cancer-related deaths are caused by cancer metastasis, in which cancer cells break away from the primary tumor, travel through the blood or lymph system as circulating tumor cells (CTCs), and form new tumors (metastases) in other parts of the body. Studies have shown that the neutralization of CTCs in circulation for the prevention of metastasis could represent an effective anti-cancer strategy. Our lab has developed a unique strategy to kill CTCs in the circulation that modifies the surface of circulating leukocytes with bispecific liposomes. The cancer-specific tumor necrosis factor (TNF) related apoptosis inducing ligand (TRAIL) is conjugated on the surface of liposomes along with a leukocyte-binding protein. The protein for binding can either be E-selectin (ES) that recognizes and binds to the majority of leukocytes, or an antibody that binds selectively to a specific subpopulation of leukocytes such as natural killer cells. These bispecific liposomes, after intravenous administration, are expected to adhere to their target leukocytes and enable them to present TRAIL on their surface for the purpose of killing CTCs. Students will learn how to make and characterize liposomes, and conjugate liposomes with proteins. They will also learn cell culture skills, cell viability assays, and fluorescence microscopy. Lastly, they will learn how to evaluate their functions in whole blood in a setting to mimic blood circulation in vivo.

Desired Qualifications:
A minimum overall GPA equivalent to B+ or better
A genuine interest in research and intellectual curiosity
Basic knowledge of chemistry or biology
 
Nature of Supervision:
Daily mentoring and supervision from graduate students, postdocs and PI; Weekly lab meeting and seminars.
 
A Brief Research Plan (period is for 10 weeks):
Week 1-3: Preparation and characterization of liposomes using liposome extruder and Zeta sizer; Formulation optimization for high colloidal stability and longer shelf life
Week 3-5: Anticancer protein conjugation, conjugation efficiency analysis and stability studies
Week 5-7: Leukocyte binding studies with viscometer and flow cytometer, formulation optimization for ideal leukocyte binding.
Week 7-10: Preparation of multiple cancer cell lines for functional studies, Evaluation of the cancer cell killing effects in whole blood in viscometer, formulation optimization for high killing efficacy

 
Number of Open Slots: 2
 
Contact Information:
Name: Michael King
Title: Wilson Professor and Department Chair
Department: Biomedical Engineering
Campus Address: Rm 346 ESB
Email: mike.king@vanderbilt.edu
Phone: (615) 875-8384