Cornell University Physical Sciences-Oncology Center
Cornell University, Ithaca, NY
Center Summary:
Cornell University Physical Sciences-Oncology Center (CU PS-OC) will use its expertise in manufacturing nano- and microfluidic devices to devise and assemble a three-dimensional tumor model to delve into cancer’s progression. This design imparts spatial and temporal resolution far greater than obtained by conventional two-dimensional tissue culture models. Moreover, this platform will facilitate monitoring non-linear responses to a combination of physical, chemical, genetic, and epigenetic stimuli. These investigators will merge the three-dimensional tumor model with cutting edge imaging techniques to investigate the impact of physicochemical factors in tumor vascularization. Along with these studies, an epigenetic and global transcriptome analysis will be carried out on the tumor model following various perturbations. This multi-disciplinary approach will yield quantitative measurements from the highly controlled tumor environment to formulate mathematical models of vascular invasion as well as to generate a better understanding of the signaling pathways that regulate the angiogenic switch.
Project 1 - Physiochemical Transducers and their Role in Tumor Angiogenesis
Project Leaders: Claudia Fischbach-Teschl (Cornell University) and Vivek Mittal (Weill Cornell Medical Center)
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Tumors consist of distinct niches and cellular crosstalk between these niches enhances tumor angiogenesis via the recruitment of bone marrow elements. This project will integrate tissue engineering, microfluidics, and mathematical modeling to recreate tumor-like niches and study the underlying extra- and intracellular signaling across multiple length scales.
Project 2 - Physical and Chemical Cues in Tumor Cell Migration
Project Leaders: Cynthia Reinhart-King (Cornell University) and Paraskevi Giannakakou (Weill Cornell Medical Center)
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Metastatic cell migration is intimately linked to the chemical and mechanical properties of the microenvironment. This project will deconvolve these contributions. It will apply quantitative and enabling new methodologies from the physical sciences to study the mechanisms underlying the spatial and temporal regulation of metastatic cell migration in 3D.
Project 3 - Adhesion of Tumor Cells in the Vascular Microenvironment
Project Leaders: Michael R. King (Cornell University) and David Nanus (Weill Cornell Medical Center)
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This project is focused on understanding the fundamental physical mechanisms of circulating tumor cell adhesion to inflamed endothelium under flow, as a critical step in the hematologic spread of metastatic cancers. It will address how the vascular microenvironment controls the recruitment and extravasation of circulating tumor cells. Micro/nanofabrication, fluid mechanics, and surface chemistry techniques will be used to accurately recreate elements of the complex in vivo microenvironment.
Core 1 - Fabrication Core
Core Leader: Graham Kerslick (Cornell University)
Nanobiotechnology center shared research facilities integrate nano-and microfabrication capabilities with biochemical processing and analysis tools in an environment designed to enhance interdisciplinary research. Facility staff members offer extensive support in problem solving throughout a research project and training in the use of tools and equipment that may be unfamiliar to them. Special workshops will be available to the PS-OC community, in microfluidic device design and fabrications, scanned probe microscopy, and surface characterization techniques for biomaterials .
The Cornell NanoScale Science & Technology Facility (CNF) is a national user facility that supports a broad range of capabilities including fabrication, synthesis, computation, characterization, and integration. These enable users to build structures, devices, and systems from atomic to complex length-scales. The CNF has dedicated Life Sciences liaison staff who give process support to users with biology-based projects and aids users with finding collaborators; this will enable PS-OC researchers to apply the tools of nano-and microfabrication to create systems to study aspects of cancer in a precise manner.
Core 2 - Selected Cell Epigenomic Analysis Core
Core Leaders: Harold Craighead (Cornell University) and Ari Melnick (Weill Cornell Medical Center)
The Core will develop processes and devices to rapidly evaluate the molecular state of a few selected cells and work toward analysis of individual cells. The Core will enable PC-OC scientists to understand the distribution of properties and to then consider the consequences of this heterogeneity in the context of various microenvironments. Services are offered in close collaboration with the CLC sequencing, microarrays and informatics cores.
Michael L. Shuler, Ph.D.
Michael Shuler is the James and Marsha McCormick Chair of the Department of Biomedical Engineering as well as the Samuel Eckert Professor of Chemical Engineering in the School of Chemical and Biomolecular Engineering at Cornell University. Shuler received his degrees in chemical engineering (BS, University of Notre Dame, 1969 and Ph.D., University of Minnesota, 1973) and has been a faculty member at Cornell University since January 1974. Shuler’s research is focused on biomolecular engineering and nanobiotechnology and includes development of an “artificial” animal (in vitro) for testing pharmaceuticals, models of the vasculature to identify interactions of circulating tumor cells with the endothelium, controlled drug delivery to treat brain tumors, production systems for useful compounds, such as paclitaxel from plant cell cultures, and computer models of cells relating physiological function to genomic structure. Shuler’s research has led to commercial processes for production of the anticancer agent, Taxol, to tools to produce proteins from recombinant DNA (the “High Five” cell line), to software to support systems biology, and to devices for drug development (HuRel system).
He has received numerous awards for his research. He has an honorary doctorate from the University of Notre Dame (2008). He has received the Amgen Award in Biochemical Engineering, the Professional Progress and Warren K. Lewis Awards from the American Institute of Chemical Engineers. Also, he was the inaugural awardee for the J.E. Bailey Award from the Society for Biological Engineering. Shuler has been elected to membership in the National Academy of Engineering and the American Academy of Arts and Science.
Barbara L. Hempstead, M.D., Ph.D.
The Co-Director and Senior Co-Investigator is Professor Barbara Hempstead, M.D. Ph.D. Dr..Hempstead is the O. Wayne Isom Professor of Medicine and Co-chief of the Division of Hematology and Medical Oncology at Weill Cornell Medical College, New York City. Dr. Hempstead is a graduate of Washington University School of Medicine, and performed her clinical training at New York Hospital-Weill Cornell Medical Center. Dr. Hempstead is Board Certified in Oncology and Hematology and is a member of the American Society for Clinical Investigation and the Association of American Physicians. Her active research effort includes the study of growth factor: receptor interactions and receptor signaling, with particular interests in how these regulate angiogenesis.
