Michelle Digman, PhD
William J. Link Chair and Professor, Department of Biomedical Engineering, University of California Irvine
Date: Friday, March 20
Time: 9–9:50 a.m.
Location: SCOB 228
Faculty host: Heather Clark
Abstract
Metabolic alterations, particularly increased glycolysis — or the Warburg effect — and atypical extracellular matrix structure, contribute to tumor aggressiveness and drug resistance. While tumor cells stiffen the ECM during progression, the direct relationship between ECM stiffness and altered metabolism remains poorly understood.
We apply phasor-based fluorescence lifetime imaging microscopy, or FLIM, to measure metabolic changes as a function of ECM mechanics. Comparing triple-negative breast cancer, or TNBC, cells to non-cancerous cells on substrates of varying stiffness, we found that TNBC exhibits decreased bound NADH fraction — which is indicative of glycolysis — with increasing substrate stiffness, while other cell lines showed minimal changes.
To investigate mitochondrial dynamics, we developed Mitometer: an unbiased algorithm for automated segmentation and tracking of mitochondria in live-cell 2D and 3D time-lapse images. Mitometer reveals that mitochondrial motility and morphology in breast cancer — but not normal breast epithelia — correlate with bound NADH fractions and features such as speed, displacement, directionality and branching. We also introduce novel hyperspectral imaging methods combined with multicolor organelle-specific staining for simultaneous multi-parametric physiological profiling of multiple organelles in live cells, applicable to both non-tumorigenic and cancerous cell lines.
View and access Mitometer on GitHub.
Biosketch
Michelle Digman is William J. Link Chair and a professor in the Department of Biomedical Engineering at the University of California Irvine. She is currently the director of the Laboratory for Fluorescence Dynamics and director of W.M. Keck Nanoimaging Lab. She served as co-equity advisor for the Henry Samueli School of Engineering for five years and biomedical engineering associate chair for Graduate Affairs for three years.
She received her Master of Science and doctorate in chemistry from University of Illinois at Chicago and did her postdoctoral work at the University of Illinois, Urban-Champaign in the Department of Physics. Digman is a Scialog Fellow and has won several awards — including the NSF-CAREER award, the Hellman Fellowship, the Fluorescence Young Investigator Award from the Biophysical Society and the Faculty Innovation in Teaching award — and has received the Henry Samueli Career Development Chair. She has coauthored over 90 peer reviewed manuscripts and six book chapters. Her current research interest focuses on quantitative spatial and temporal correlation spectroscopy, protein dynamics during cell migration, characterizing metabolic alterations in cells and tissues, and developing novel imaging technologies.
In addition to research and teaching, Digman is passionate about community outreach. She initiated the outreach program for minority community college students and outstanding high school students called Undergraduate Student Initiative for Biomedical Research, or USIBR, which has been in operation since 2011. Her goals are continuing with a strong, collaborative and productive laboratory; engaging in growth and development of her research group through targeted teaching and mentoring; and aiding in the strategic growth of the University through service, increased diversity initiatives and collaboration.
