Koch Institute Luria Auditorium (76-156) and Zoom (see below for full information)
A blood exchange method to study circulation kinetics of tumor cells in the blood
Blood is an essential compartment for tumor cell trafficking. In solid epithelial-derived tumors, blood serves as the major vehicle for metastasis, whose principal cell is the circulating tumor cell (CTC). In liquid blood-based cancers, the blood is a major reservoir of disease and allows cells to move between sites around the body. While the general steps of these processes are known, there is a lack of evidence in the field regarding the physical properties defining tumor cell trafficking through the blood. Studying these parameters is crucial to understanding the nature of the metastasis, which remains the leading cause of cancer deaths.
In this thesis, we begin by developing a system to determine circulation properties of CTCs. Using a series of real-time CTC detection platforms developed in our lab, we create a model to describe how the exchange of blood between healthy and tumor-bearing mice allows us to extrapolate circulation properties of the cells. Next, we apply this platform to study the circulation kinetics of CTCs from several models of solid-tumor disease. Finally, we use these techniques to study the kinetics of leukemia cells. By varying the tumor and treatment status of donor and recipient animals, we assess how the tumor cells themselves and the microenvironment of the bone marrow impacts tumor cell clearance. We discover that E-selectin, a vascular adhesion molecule, prevents cell turnover between tumor compartments and enables relapse cells to escape circulation more quickly.
Altogether, this work provides a novel method to assess circulation kinetics of tumor cells and identify features that regulate the clearance of tumor cells from the blood.
Thesis Supervisor:
Scott R. Manalis, PhD
David H Koch Professor, Biological Engineering and Mechanical Engineering, MIT
Thesis Committee Chair:
Sangeeta N. Bhatia, MD, PhD
John J. and Dorothy Wilson Professor, Electrical Engineering & Computer Science and Institute for Medical Engineering & Science, MIT
Thesis Readers:
Michael Hemann, PhD
Associate Professor, Biology, MIT
David Weinstock, MD
Vice President of Discovery Oncology, Merck
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Topic: Alex Miller's Thesis Defense
Time: Tuesday, April 4, 2023 9:30 AM Eastern Time (US and Canada)
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