Mitochondria Morphology as a Biomarker of Cancer Phenotype and Drug Response

Wednesday, February 8, 2017

11:00am - 12:00pm


Dr. Randy J. Giedt
Massachusetts General Hospital/Harvard Medical School, Boston, MA

Abstract:

Mitochondria, critical organelles in quiescent and dividing cells, have been shown to vary in number, mass and shape. While previous work has focused on understanding molecular mechanisms underlying changes in normal and immortalized cells, less is known about longer term mitochondrial behavior such as a morphological pattern heterogeneity and precisely what role this heterogeneity plays in cancer initiation, development, response to treatment, and ultimately patient prognosis. Here, we have developed an image based analytical technique to phenotype mitochondrial morphology in different cancers, including in vitro cancer cell lines and patient derived cancer cells. Our methodology is based on a combination of novel, clinically relevant collection and fixation techniques and advanced image processing and computer learning analysis methodologies. Using these methods, we illustrate functionally significant mitochondrial heterogeneity between cell lines as well as patient derived xenograft
samples. Furthermore we find that differing classes of drugs differentially affect mitochondrial function and phenotype. From this work, we hypothesize that mitochondrial phenotype may be a sensitive marker of response to drug therapy with possible clinical relevance.

 

Biography:

Dr. Giedt holds a bachelor's degree in Mechanical Engineering from South Dakota State University.  He earned an M. S. and PhD in Biomedical Engineering from the Ohio State University.  He is currently a research fellow at the Center for Systems Biology at Massachusetts General Hospital, Harvard Medical School, where his research interests involve utilizing engineering and imaging approaches to understand how chemotherapies work or fail in tumors in a variety of models.