Arizona State University Physical Sciences-Oncology Center's (ASU PS-OC) foremost aim is to rigorously question the central tenets of cancer biology and to innovate paradigm shifting tactics that challenge the barriers of contemporary cancer research and treatments. These investigators hypothesize that cancer progression is linked to systematic physical differences in cells. Pioneering methods to survey these physical changes will be employed by this center, and theoretical evolutionary models will also be applied to establish the evolution of a metastatic cancer cell from a physical context. Moreover, the strategic partnership of distinguished scientists in cancer biology, clinical oncology and physics will lend to the technical advances introduced from this center. Along this line, these investigators have spearheaded single-cell tomography, which has isotropic 100 nm resolution and enables three-dimensional imaging of single cells. This center will use single-cell computerized tomography to characterize physical changes as potential cancer signatures.
Principal Investigator: Paul Davies, Ph.D.
Senior Scientific Investigator: William M. Grady, M.D.
Collaborators: Fred Hutchinson, Cancer Research Center, Mayo Clinic - Scottsdale
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Paul Davies, Ph.D.
Paul Davies is Director of The Beyond Center for Fundamental Concepts in Science at Arizona State University. He is a theoretical physicist, cosmologist and astrobiologist with research experience ranging from the origin of the universe to the origin of life. He is noted for his work on the theory of quantum fields in curved spacetime, the thermodynamics of black holes, early-universe cosmology, the arrow of time, the nature of the laws of physics and the emergence of life in the universe.
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William M. Grady, M.D.
William Grady is the section chief of Gastroenterology at the Member University of Washington Medical Center and the Roger C. Haggitt Associate Professor of Medicine. He is also an Associate of the Clinical Research Division at the Fred Hutchinson Cancer Center and the Medical Director of the Gastrointestinal Cancer Prevention Program at the Seattle Cancer Care Alliance. His work on the role of epigenetic and genetic alterations in gastrointestinal cancer has led to the discovery of novel biomarkers that can be used as early detection and as prognostic markers for colon cancer. His research is funded by the NIH through the NCI and Early Detection Research Network. More Info
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Deirdre R. Meldrum, Ph.D.
Deirdre R. Meldrum is Dean of the Ira A. Fulton Schools of Engineering, is also Professor of Electrical Engineering, and Director of the Center for Biosignatures Discovery Automation at the Biodesign Institute at Arizona State University. In addition, Meldrum directs a National Institutes of Health Center of Excellence in Genomic Science called the Microscale Life Sciences Center. Her research interests include genome automation, live single cell analyses, microscale systems for biological applications, ecogenomics, robotics and control systems for applications to human health and disease and the oceans. She served on the National Advisory Council for Human Genome Research. More Info / Team Members
Stuart Lindsay, Ph.D.
Stuart Lindsay is Edward and Nadine Carson Professor of Physics and Chemistry and Director of the Center for Single Molecule Biophysics in the Biodesign Institute. His research focuses on biology at the nanoscale. He was a co-founder of Molecular Imaging Corporation. His textbook “Introduction to Nanoscience” has just been published by Oxford University Press. More Info / Team Members
Robert Ros, Ph.D.
Robert Ros is Associate Professor for Physics at Arizona State University. He joined ASU in 2008 from Bielefeld University as Associate Professor for Physics. He is an experimental biophysicist with expertise in force spectroscopy, and the combination of AFM with confocal microscopy. His research interests in the field of nanobiophysics includes structural biology, physics of molecular recognition, conformational dynamics of single (bio-)molecules and cell mechanics using scanning probe methods, force spectroscopy technologies, fluorescence microscopy, and nanophotonics. More Info / Team Members
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When cells become cancerous and progress towards malignancy their physical properties change in distinctive and systematic ways. Cancer cells are generally softer and geometrically more distorted than healthy cells. In addition, their molecular architecture changes. We have a variety of experimental projects aimed at measuring these changes, from a molecular scale up to tissues, in an effort to understand how they affect the growth and spread of tumors. On the theoretical side, we are seeking a comprehensive theory of cancer by tracing its ancient evolutionary roots, back to the dawn of multicellularity, and relating the re-expression of ancient traits to the physical changes studied in our experimental program.
Project 1 - Quantitative Mechanical Nanotomography of Cells Embedded in 3D-Matrices
Project Leader: Robert Ros (Arizona State University)
Because cells are highly heterogeneous on the nanometer scale, new techniques of finite element analysis are needed to create mechanical nanotomography maps. This project will utilize truly innovative approaches for the quantitative analysis of the mechanical properties of both cells and extracellular matrix (ECM) embedded in 3D matrices. The unique feature of this project is the use of AFM and optical imaging in combination to construct and compare 3D elasticity maps of healthy and cancer cells, as well as ECM, and the Project will create complex data sets that define the mechanical parameters for cells, and contribute significant input to the Mathematical and Computational Modeling Core.
Project 2 - Probing the Physical Properties of Nucleosomes during Cancer Progression
Project Leader: Steven Henikoff (The Fred Hutchinson Cancer Research Center)
This project will characterize the cancer cell lines and tissues common to the Center using newly developed single-molecule tools, together with new methods for chromatin fractionation based on physical properties of mononucleosomes and arrays, to probe chromatin and epigenetic changes in cancer. We propose that gene silencing occurs because DNA methylation and other epigenetic modifications interfere with incorporation or properties of the universal histone variant, H2A.Z. Our project will apply atomic force microscopy (AFM) and recognition imaging technologies that we have recently used to characterize single native chromatin particles containing the CenH3 histone variant in an ongoing ASU-Hutch collaboration.
Project 3 - Single Cell Physiology and 3D Tomography
Project Leader: Deirdre Meldrum (Arizona State University)
This project applies two novel technologies to quantify cancer cell phenotypes using cell lines and cells disaggregated from human biopsies. The first novel technology is a hermetically-sealed microenvironmental chamber that allows respiration rate and ion flux measurements; the second is an optical CT scanner for 3D cell imaging that facilitates extraction of nuclear morphometric features. We will correlate physiological and morphometric variables with transcription profiles measured using quantitative Reverse Transcriptase-PCR, and seek to understand relationships between our measurements and our sister projects on chromatin structure and cell mechanical properties.
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Core 1 - Beyond Center
Core Leader: Paul Davies (Arizona State University)
This core will act as the conceptual driver for the entire Center, and will also provide a resource for the PS-OC network and the wider scientific community. In addition to managing the Center’s overall program and facilitating collaboration, innovation and a distinguished visitor program, it will host a Cancer Forum. The prime activity of the Forum will be to act as a “think tank,” by hosting three workshops per year on cutting edge topics related to the intersection of physical science and cancer.
Core 2 - The Materials Core
Core Leader: William Grady (The Fred Hutchinson Cancer Research Center)
The Materials Core comprises the Fred Hutchinson Cancer Research Center and the Mayo Clinic, Scottsdale; the former will provide well-characterized cell lines for the three experimental projects from different stages of cancer progression, and also support the development of common reagents. As permitted by resource availability, the cell lines will be altered through gene transfection by inserting specific oncogenes or deleting specific tumor suppressor genes known to be relevant to cancer pathogenesis in order to assess the effect of the mutant genes on the physical properties assessed. The Mayo Clinic will coordinate the collection and characterization of primary tissues and make them available for the projects.
Core 3 - Mathematical and Computational Modeling Core
Core Leader: Timothy Newman (Arizona State University)
The third core focuses on large-scale computational modeling of biological and physical processes relevant to cancer progression. Modeling will be performed primarily by Timothy Newman and his group in the ASU Center for Biological Physics (CBP), and coordinated locally with experimental projects 1 (AFM probe of cancer cell material properties) and 3 (tomography of distorted nuclei in cancer cells) while large-scale computations will be implemented in collaboration with the ASU High Performance Computing Initiative (HPCI). Newman has developed the Subcellular Element Model (SEM), which is an algorithm designed to simulate large multicellular systems, with special attention to the three-dimensional nature of cell deformations and biomechanics.
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Our workshops bring scientists of diverse fields together to contemplate many aspects of cancer. Each workshop has its own webpage, where one can find recorded interviews with the participants, transcripts of those interviews, recorded summaries of the talks and pictures.
Every other Thursday the ASU PS-OC holds seminars in the Biodesign Auditorium. This page offers a listing of past and upcoming seminars as well as links to the recordings of past seminars and links to the live webcast feed of upcoming seminars.
These spotlight videos focus in on our projects and the kinds of tools we use to research the roots of cancer. Tasks like studying epigenetic control and differentiating normal from cancerous cells are implemented through a physics approach. Videos include the projects of Stuart Lindsay, Robert Ros and Tim Newman.
Science correspondent Tom Feilden reports on the new approach to cancer research pioneered by scientists at Arizona State University. Tom interviewed both Paul Davies, Director of The Beyond Center for Fundamental Concepts in Science and Roger Johnson, Research Scientist at the Center for Biosignatures Discovery Automation at the Biodesign Institute at Arizona State University.
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