Event
BIOE Seminar: David Odde
Friday, October 11, 2019
9:00 a.m.-10:00 a.m.
A. James Clark Hall, Room 2132
Emily Rosenthal
301 405 3936
erosent1@umd.edu
Dr. David Odde
Professor
Department of Biomedical Engineering
University of Minnesota
Mechanics of Glioma Mouse Models of Human GBM Subtypes
Glioblastoma (GBM) is the most common form of malignant gliomas with a median survival of 15 months and a 5-year survival rate of less than 5%. GBM is currently incurable due to the high proliferation and migration rates associated with tumors cells, which allow them to invade healthy tissue and evade current therapies. High-grade gliomas have been classified into three subtypes: proneural, mesenchymal, and classical. However, how the genetic drivers influence cell dynamics and thereby impact disease progression remains unknown. In my seminar I will describe how, using the Sleeping Beauty (SB) transposon system to induce two genetically-distinct cohorts of tumor-bearing mice by overexpressing NRASG12V or PDGFβ, in combination with SV40-lgTA, we found that these brain tumors recapitulate features of human high-grade gliomas with distinct survival and growth rates. Ex vivo time-lapse imaging of tumor-bearing brain slices shows NRASG12V driven tumor cells migrate faster (RMC ~40 ±12 µm2/hr) than PDGFβ (RMC ~4 ±1 µm2/hr). Like human mesenchymal subtype, both transcriptomic and histological analyses show NRASG12V-driven tumors have higher immune cell infiltration and elevated expression of immune gene signature. Furthermore, isolated primary glioma lines from each cohort exhibit similar migration phenotype in organotypic slice culture in healthy mouse brain slices. Using the Cell Migration Simulator, we hypothesize that changes in the number of molecular clutches (adhesivity) can explain the migration differences. In summary, we developed and characterized two induced glioma mouse models, in immune competent mice, resembling human proneural and mesenchymal GBM subtypes setting the stage for subtype-specific therapy development.
David Odde is the Medtronic Endowed Professor of Engineering in Medicine at the University of Minnesota. Trained as a chemical engineer, Odde joined the newly created Department of Biomedical Engineering at the University of Minnesota in 1999 where he is a professor and Associate Director for Strategic Research Initiatives in the Institute for Engineering in Medicine. In his research, Odde’s group builds computer models of cellular and molecular self-assembly and force-generation-dissipation dynamics, and tests the models experimentally using digital microscopic imaging of living cells ex vivo and in engineered microenvironments. Current applications include modeling the molecular mechanisms of neurodegeneration and of cancer cell migration through complex mechanical environments such as the brain. His group seeks to bring an engineering approach that uses physics-based modeling and analysis to understand, predict, and control disease outcomes (oddelab.umn.edu). Dr. Odde is an elected Fellow of the American Institute for Medical and Biological Engineering (AIMBE), the Biomedical Engineering Society (BMES), the International Academy of Medical and Biological Engineering (IAMBE), and the American Association for the Advancement of Science (AAAS) and is the Director of the Physical Sciences in Oncology Center at the University of Minnesota (psoc.umn.edu), which is focused on modeling the mechanics of cancer cell migration in biologically relevant contexts.
