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Investigating the Tumor and Tissue Microenvironment After Therapy

Primary Investigators:
Marjan Rafat
Brief Description of Project:
Previous studies have found that immunocompromised patients are more susceptible to breast cancer recurrence following radiation damage. In pre-clinical mouse models, radiation enhances both macrophage infiltration and tumor cell recruitment to normal tissues in the absence of CD8+ T cells. The mechanisms by which tumor cells can be attracted to damaged sites are largely unknown. Understanding these mechanisms can help breast cancer patients prevent local recurrence. This project has two goals: 1. to determine how changes in the extracellular matrix after radiation influence tumor cell recruitment, and 2. to evaluate how secreted factors regulate macrophage and tumor cell behavior after radiation damage.

Desired Qualifications:
The Rafat Lab is accepting undergraduate students who would like to conduct breast cancer research. Serious consideration will be given to students who have a strong interest in pursuing a future PhD or MD/PhD. A minimum GPA of 3.5  and knowledge of basic research approaches are favored but not required.
Nature of Supervision:
Students will be supervised by Dr. Rafat directly regarding research goals. They will meet with her individually to evaluate research progress. She will assist them in literature searches initially to provide information about selecting appropriate and relevant papers with the goal that they will learn to do so on their own. She will provide feedback on bi-weekly written reports that serve to enhance the students' scientific communication skills. In addition to Dr. Rafat's supervision, undergraduate students will be supervised by graduate students working in the Rafat Lab. These graduate students will supervise them on a daily basis to ensure that their concerns can be addressed, their questions are being answered, and research is being conducted in a safe and responsible manner. This supervision is intended not only for the undergraduates to use proper techniques but also for them to learn how to think critically and creatively to prepare them for a potential research career.
A Brief Research Plan (period is for 10 weeks):
Students will participate in one of two areas. In one area, students will evaluate the effect of radiation on the extracellular matrix (ECM) in normal tissues by performing immunohistochemistry. Characteristics in pre-irradiated tissues will be compared to tissues damaged by radiation over a time period of 10 days. Students will be able to image the stained slides, quantify the images, and analyze the data to determine how radiation-induced changes in the ECM influence tumor cell recruitment. Students will also evaluate how the ECM alters tumor cell behavior by fabricating ECM hydrogels that mimic in vivo changes after irradiation, which will be used to determine the effect on tumor cell proliferation, migration, and invasion. In the second arm of the project, students will probe differences in normal tissue cytokine secretion following radiation in immunocompromised and immunocompetent mice. Previous studies indicate that CD8+ T cells regulate the infiltration or proliferation of macrophages into damaged tissues, so students will evaluate how CD8+ T cell removal and macrophage infiltration alter secreted factors in damaged tissues through analyzing data from Luminex immunoassays. To test these factors, students will optimize and perform invasion and chemotaxis assays using conditioned media from control and irradiated fibroblast and adipocyte cells to determine how the radiation response of normal cells influences tumor and immune cell behavior. The students will learn how to image fluorescent and migrating cells, quantify migration and proliferation, and analyze data to determine the mechanisms by which radiation regulates tumor and immune cell dynamics. Finally, all students will have the opportunity to present their independent research findings at laboratory meetings.
Number of Open Slots: 2
Contact Information:
Name: Marjan Rafat
Title: Assistant Professor
Department: Chemical and Biomolecular Engineering
Campus Address: ESB 426
Phone: (615) 343-3899