BME Seminar Series: Dr. Margaret Bennewitz, West Virginia University

Margaret Bennewitz, PhD
Assistant Professor
Chemical and Biomedical Engineering
West Virginia University

"Tracking breast cancer with NEMO’s switchable MRI signal and fluorescence microscopy"

Abstract:

Misdiagnosis is prevalent in young, high-risk women with dense breasts receiving breast cancer screening, resulting in needless follow-up testing, anxiety and medical costs. Compared to mammography, magnetic resonance imaging (MRI) detects more breast cancers but still suffers from high false positive rates due to the conventional contrast agents used, e.g., gadolinium (Gd)-chelates. Gd is retained within patients after MRI scans and causes toxicity. The poor performance of Gd-chelates results from their lack of targeting and constant MRI signal which highlights both benign and malignant tumors. We have developed Nano-, Encapsulated Manganese Oxide (NEMO) particles that will provide superior replacements for Gd-chelates. Our preliminary data shows that NEMO particles provide a unique pH-switchable signal that is only activated upon internalization in acidic tumor cell endosomes. NEMO particles are decorated with a tumor targeting peptide which is overexpressed exclusively on breast cancer cells to ensure specificity. Furthermore, NEMO particles are safely tolerated in vivo and have a stronger signal vs. Gd-chelates.  NEMO particles are expected to greatly reduce the misdiagnosis of breast MRI and are widely applicable to other tumor types.

A majority of breast cancer deaths are due to metastasis from the breast to distant organs including lungs. The mechanisms by which tumor cells become trapped within the pulmonary microvasculature and extravasate into the surrounding tissue have yet to be fully defined. Intravital imaging offers unique advantages over conventional techniques, including the ability to image in real-time and in a live physiologic microenvironment. The Bennewitz Lab has pioneered a revolutionary live lung imaging technique called quantitative fluorescence intravital lung microscopy (qFILM) that can track cell-cell interactions in the bloodstream of mice. By utilizing qFILM and ex vivo cell imaging, we are investigating a new mechanism for breast cancer metastasis whereby neutrophils and platelets interact with tumor-released particles called extracellular vesicles (EVs) to promote breast cancer colonization in lungs through DNA fiber release. We have observed that EV phenotype evolves with tumor development and future studies are aimed at defining EV cargo for novel targets of metastatic inhibition.

Bio:

Dr. Margaret Bennewitz received her BS degree in Bioengineering from the University of Pittsburgh in 2007 and her PhD from Yale University in Biomedical Engineering in 2012. At Yale, she specialized in MRI cell tracking and contrast agent development for the diagnosis of glioblastoma multiforme. After completing her doctorate, Dr. Bennewitz accepted a postdoctoral fellowship in the M+Visión Program, a collaborative venture between the Massachusetts Institute of Technology and hospitals and laboratories in Madrid, Spain. One of her projects involved the early detection of ovarian cancer through identifying characteristics of precursor lesions that could be imaged using optical microscopy. During her second postdoctoral fellowship at the University of Pittsburgh, Dr. Bennewitz developed an in vivo multiphoton microscopy technique (qFILM) for visualizing blood cell trafficking within the pulmonary microcirculation of live sickle cell disease mice and received an NIH NRSA F32 Fellowship to pursue this work. Dr. Bennewitz joined the faculty at West Virginia University as an Assistant Professor in the Department of Chemical and Biomedical Engineering in August 2017. Dr. Bennewitz is utilizing the complementary qualities of MRI and in vivo fluorescence imaging to study breast cancer in her research group.