This application is organized around the framework of Spatio-Temporal Organization of Chromatin and Information Transfer in Cancer. The organizing framework of the CR-PSOC integrates the strengths of chemistry, genetics, and physics to address chromatin dynamics in cancer. Through the use of shared model systems Center investigators will be able to integrate data from across projects to develop a new conceptual understanding of the mechanisms underlying physical rearrangement of chromatin in cancer and how that controls gene expression. The Center is composed of three interrelated project areas, each focused on different aspects of chromatin structure and function. Each project integrates emerging physical science approaches and molecular and cancer cell biology tools, as well as theory and modeling methods from the physical sciences, to achieve a quantitative and predictive understanding of the of deregulation of chromatin mechanics, epigenetic regulatory pathways, gene expression, and the nuclear environment in cancer. The Center's projects maintain a clear cancer focus rooted in understanding the molecular mechanism behind genetic alterations in chromatin regulators in cancer, particularly hematological malignancy. The scientific activities of the CR-PSOC will be supported by two shared resource cores: the Nanocytometry Core and the PDX Human Tumor Model Core. These cores will encompass unique resources that will not only benefit CR-PSOC investigators but will substantially augment the tools and approaches of investigators across the PSON. The proposed Chicago Region-Physical Science Oncology Center (CR-PSOC) brings together a unique constellation of physical science, chemical biology, and genetics expertise and couples this expertise with cutting edge analytical instrumentation, specialized sequencing technology, super high resolution imaging modalities, and novel cancer model systems. This combination of expertise and resources will enable Center investigators and members of the PSO Network to examine the structural and functional aspects of chromatin and nuclear dynamics in cancer at unprecedented depth and breadth. The CR-PSOC will provide a range of educational activities and programs designed to stimulate the interest and enhance the capabilities of the next generation of researchers working at the frontiers of physical science and oncology. Through integration of a patient advocate into Center administration with a key role in advising and supporting the translation of CR-PSOC discoveries the Center will maintain a steady focus on the importance of targeting clinical outcomes through advances in basic research.

Public Health Relevance

The proposed Chicago Region Physical Science Oncology Center will combine the tools and perspectives of chemistry, genetics and physics to develop a comprehensive description of the mechanical and molecular changes in nuclear packaging of DNA in cancer with the goal of identifying potential new targets for therapeutic intervention. Average Scores of the Components: Overall: 2.5 Project 1: 2.5 Project 2: 2.7 Project 3: 3.8 Resource Core 1: 2.8 Resource Core 2: 2.4 Education and Outreach: 1.5

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA193419-02
Application #
9070573
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Kuhn, Nastaran Z
Project Start
2015-05-19
Project End
2020-04-30
Budget Start
2016-05-01
Budget End
2017-04-30
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Pharmacology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Skoruppa, Enrico; Nomidis, Stefanos K; Marko, John F et al. (2018) Bend-Induced Twist Waves and the Structure of Nucleosomal DNA. Phys Rev Lett 121:088101
Dong, Hongxin; Zhu, Mengyi; Meng, Liping et al. (2018) Pumilio2 regulates synaptic plasticity via translational repression of synaptic receptors in mice. Oncotarget 9:32134-32148
Erba?, Aykut; de la Cruz, Monica Olvera; Marko, John F (2018) Effects of electrostatic interactions on ligand dissociation kinetics. Phys Rev E 97:022405
Gong, Yixiao; Lazaris, Charalampos; Sakellaropoulos, Theodore et al. (2018) Stratification of TAD boundaries reveals preferential insulation of super-enhancers by strong boundaries. Nat Commun 9:542
Haber, Aleksandar; Molnar, Ferenc; Motter, Adilson E (2018) State observation and sensor selection for nonlinear networks. IEEE Trans Control Netw Syst 5:694-708
Gunn, Kathryn H; Marko, John F; Mondragón, Alfonso (2018) Single-Molecule Magnetic Tweezer Analysis of Topoisomerases. Methods Mol Biol 1703:139-152
Stephens, Andrew D; Liu, Patrick Z; Banigan, Edward J et al. (2018) Chromatin histone modifications and rigidity affect nuclear morphology independent of lamins. Mol Biol Cell 29:220-233
Tocco, Vincent J; Li, Yuan; Christopher, Keith G et al. (2018) The nucleus is irreversibly shaped by motion of cell boundaries in cancer and non-cancer cells. J Cell Physiol 233:1446-1454
Gladstein, Scott; Stawarz, Andrew; Almassalha, Luay M et al. (2018) Measuring Nanoscale Chromatin Heterogeneity with Partial Wave Spectroscopic Microscopy. Methods Mol Biol 1745:337-360
Brahmachari, Sumitabha; Dittmore, Andrew; Takagi, Yasuharu et al. (2018) Defect-facilitated buckling in supercoiled double-helix DNA. Phys Rev E 97:022416

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