Arizona State University Physical Sciences-Oncology Center
Arizona State University, Tempe, AZ
Center Summary:
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.
Project 1 - Quantitative Mechanical Nanotomography of Cells Embedded in 3D-Matrices
Project Leader: Robert Ros (Arizona State University)
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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)
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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)
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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.
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.
Paul Davies, Ph.D.
Paul Davies is a British-born theoretical physicist, cosmologist, astrobiologist and best-selling author. He is Director of the Beyond Center for Fundamental Concepts in Science and Co-Director of the Cosmology Initiative, at Arizona State University. His research focuses on the “big questions” of existence, ranging from the origin of the universe to the origin of life and the nature of time. He helped create the theory of quantum fields in curved spacetime, which provided explanations for how black holes can radiate energy, and what caused the ripples in the cosmic afterglow of the big bang. He was a forerunner of the theory that life on Earth may have come from Mars, and is currently championing the proposal to seek a “shadow biosphere” on Earth as evidence for multiple origins of life. Davies is known as a passionate science communicator. His popular books are noted for presenting complex ideas in accessible terms, and include The Mind of God, About Time, How to Build a Time Machine, The Origin of Life and The Goldilocks Enigma. His latest book, The Eerie Silence: Are We Alone in the Universe? celebrates the 50th anniversary of SETI (the Search for Extraterrestrial Intelligence), and will be published in April. Paul Davies is a Member of the Order of Australia and a recipient of the Templeton Prize, the Kelvin Medal, and the Michael Faraday Prize from The Royal Society. The asteroid 1992 OG was officially named (6870) Pauldavies in recognition of his work on cosmic impacts.
William M. Grady, M.D.
Dr. William Grady is the section chief of Gastroenterology at the University of Washington Medical Center and the Roger C. Haggitt Associate Professor of Medicine. He is also an Associate Member 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. He has an active research program studying the role of epigenetic and genetic alterations in gastrointestinal cancer. This work has led to the discovery of novel biomarkers that can be used as early detection and as prognostic markers for colon cancer. His studies of the role of epigenetics and genetics in gastrointestinal cancer have been published in Nature Genetics, Cancer Research, Clinical Cancer Research, Human Mutation, Genes, Chromosomes, and Cancer, the International Journal of Cancer, and other journals. He is the recipient of several prestigious awards for his research including a Damon Runyon Lilly Clinical Investigator Award, Mallinckrodt Scholar Award, Presidential Early Career Award for Scientists and Engineers, and a Burroughs Wellcome Award for Clinical Scientists in Translational Research. His research is funded by the NIH through the NCI and Early Detection Research Network.
