Understanding the Process: Metabolism of Tumors
From the Radiology Department Newsletter, Editor: Mary McAllister


To be able to say, 30 or 40 years from now, “I was a part of this work that led to better diagnosis and therapy for cancer,” is a dream of Dr. Kristine Glunde, Assistant Professor in the Johns Hopkins University In Vivo Cellular and Molecular Imaging Center (ICMIC) and Division of Magnetic Resonance Research. And her work for the last eight years at Hopkins just might move her closer to that goal.

When she arrived at Hopkins from Bremen, Germany, back in 2000, one of her fields of interest was brain metabolism, but, once here, she switched to cancer research, and is now working on at least three major projects— choline metabolism in cancer, tumor hypoxia signaling pathways, and the biology of lysosomes.

Dr. Kristine Glunde


Dr. Glunde is studying the choline metabolism of cancer in collaboration with Dr. Zaver Bhujwalla and Dr. Michael Jacobs. “We are looking at this process because it’s tied to the detection of the total choline signal,” she says. “In breast tumors, we think that a high choline signal is indicative of metastasis, and this is being tested in several clinical trials.” She cites the excellent mentorship of Dr. Bhujwalla and the establishment of the molecular imaging program here.

The second major project, which was funded by National Institutes of Health, involves “as yet unknown hypoxia-driven signaling pathways in the tumor microenvironment,” she said. Since little is known about the molecular pathways that are affected by tumor hypoxia, and since hypoxia is associated with tumor progression, a greater risk of metastatic spread and resistance to therapy, Dr. Glunde wanted to explore these processes through combined magnetic resonance spectroscopic imaging (MRSI), cutting edge mass spectrometry imaging (MSI) and targeted proteomics strategies. In collaboration with Dr. Ron M. A. Heeren in Amsterdam, she will use this multi-modal molecular imaging to investigate hypoxia in breast tumors and other types of tumors. “This project will provide technology development in the form of new cutting-edge molecular imaging tools, with the mass spectrometry imaging translated to the clinic as an add-on to pathology, and, we will obtain spatially resolved information on proteins and small molecules that are up- or down-regulated in hypoxic areas of tumors and then, target these to test the relevance with small interfering RNA,” she explained.

Originally funded by a career development award through the JHU ICMIC Program followed by an R21 Exploratory/Developmental Research Grant Award from the NIH, Dr. Glunde is now applying for an NIH RO1 Research Project Grant Program to study lysosomes as key mediators of protease routing, regulation, and secretion. “One of our hypotheses is that lysosomes fuse with plasma membranes to secrete proteases, thus enabling invasion and metastasis,” she explained. “We have developed new methods to optically image lysosomes in living human breast cancer cells, and to quantitate specific lysosomal parameters.”

The significance of this work is that if this invasion process can be disrupted, then new therapies can be developed to treat breast cancer. She is collaborating with Dr. Yu Chen, who is developing a tomographic method of fluorescence optical imaging. Dr. Chen is an Assistant Professor at the University of Maryland.

“I love collaborating with other scientists,” Dr. Glunde said. “I have great colleagues here at Hopkins, and it’s a really good fit with this team.” Her goals are to stay in academic medicine, and to make some of those breakthrough discoveries she dreams of.