The Cornell Center on the Microenviroment & Metastasis combines expertise in biomedical engineering and clinical research to address and understand the interaction of mechanical forces and chemical cues in cancer metastasis. Our researchers use expertise in fabricating nano- and microfluidic devices to model the tumor environment in three-dimensions. This approach imparts spatial and temporal resolution far greater than obtained by conventional two-dimensional tissue culture models and allows monitoring non-linear responses to a combination of physical, chemical, genetic, and epigenetic stimuli. Our researchers merge these three-dimensional tumor models with advanced imaging techniques to investigate the impact of physicochemical factors in tumor vascularization. Along with these studies, an epigenetic and global transcriptome analysis is underway on the tumor model following various perturbations. This multi-disciplinary approach is yielding 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.
Principal Investigator: Michael L. Shuler, Ph.D.
Senior Scientific Investigator: Barbara L. Hempstead, M.D., Ph.D.
Collaborators: University at Buffalo, Weill Cornell Medical Center
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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.
Dr. Barbara Hempstead is the Senior Co-investigator and Center Co-Director, the O. Wayne Isom Professor of Medicine, and Associate Dean for Faculty Development at Weill Cornell Medical College, New York. Dr. Hempstead is a board-certified medical oncologist and hematologist and the principal investigator for numerous NIH research grants. Her research effort focuses on the study of growth factors, neurotrophins. She is evaluating the role of neurotrophins in regulating vessel growth, stabilization and regression, in models of vascular development and in tumors. She is a member of the Internal Advisory Board for the New York-Presbyterian-Weill Cornell Cancer Center, is on the Board of Scientific Counselors for NICHD and has chaired international meetings in her area of research interest.
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Claudia Fischbach-Teschl, Ph.D.
Claudia Fischbach-Teschl joined the Cornell faculty in 2007. She holds a M.S. from Ludwigs-Maximilians-University in Munich, Germany and a Ph.D. in Pharmaceutical Technology from the University of Regensburg, Germany. She conducted her postdoctoral work at the University of Michigan and in the School of Engineering and Applied Sciences at Harvard University. Fischbach-Teschl's research utilizes biomaterials and biomedical engineering approaches to both analyze and therapeutically target microenvironmental conditions in tumors. She is a project leader of Cornell's Physical Sciences Oncology Center and directs activities related to studying 'The role of physicochemical transducers in the tumor angiogenic switch'.
Vivek Mittal, Ph.D.
Vivek Mittal is an Associate Professor of Cardiothoracic Surgery and the Director of the Neuberger Berman Lung Cancer Laboratory in the Department of Cardiothoracic Surgery at Weill Cornell Medical College in New York, NY. Prior to joining Weill Cornell Medical College, Dr. Mittal was an Assistant Professor at the Cold Spring Harbor Laboratory on Long Island, NY. Dr. Mittal's major focus of research has been to address the contribution of the bone marrow-derived microenvironments in primary tumor growth, metastasis initiation and progression. His lab has demonstrated that bone marrow-derived progenitor cells contribute to the "angiogenic switch" in primary tumor growth and in the progression of micrometastases to life threatening macrometastases in the lung. Dr. Mittal's lab also developed and utilized gene expression and RNAi technologies that can be used with bone marrow transplantation approaches to silence any gene in the BM compartment in vivo in mice. Dr. Mittal is a PI on RCA, R01, and STARR Cancer Consortium grants and has served on several advisory and review boards. He lectures widely to diverse audiences throughout the world and has been published in leading journals including Science, Nature, Cancer Cell, PNAS, and other leading peer-reviewed journals and text books. His research is supported by funds from the National Cancer Institute and private foundations, and several patents have emerged from his discoveries. Dr. Mittal is a Co-PI in project 1 and will focus on the effects of vascular niche characteristics on bone marrow progenitor recruitment and signaling using tissue engineering and microfluidics.
Cynthia Reinhart-King, Ph.D.
Cynthia Reinhart-King is an Assistant Professor in the Department of Biomedical Engineering at Cornell University. She is Thrust Leader of Project 2 of the Cornell PSOC, directing the investigation of the Physical and Chemical Cues in Tumor Cell Migration. Prior to coming to Cornell, she obtained her undergraduate degrees at MIT in Chemical Engineering and Biology where she was awarded the Randolph G. Wei Award for outstanding undergraduate research. As a graduate student at the University of Pennsylvania in the Department of Bioengineering, she held a prestigious graduate Whitaker Fellowship. She then worked as an individual NIH NRSA postdoctoral fellow in the Department of Medicine at the University of Rochester. Dr. Reinhart-King's research expertise is in the area of cell mechanics and cell-matrix interactions. Her lab uses a multi-disciplinary approach, implementing tools from cell and molecular biology, biophysics, chemistry and mechanics to quantitatively examine the physical mechanisms of tissue formation and disease progression. Since arriving at Cornell in 2008, she has received multiple awards, including an NSF Career Award, the Rita Schaffer Young Investigator Award from the Biomedical Engineering Society and the Sonny Yau '72 Excellence in Teaching Award from the Cornell College of Engineering.
Paraskevi Evi Giannakakou, Ph.D.
Paraskevi Evi Giannakakou is Associate Professor of Pharmacology in Medicine in the Department of Medicine, Division of Hematology and Medical Oncology at Weill Cornell Medical College of Cornell University, New York, New York. She received her PhD in Pharmacology from University of Athens School of Medicine, Athens, Greece and the National Cancer Institute, National Institutes of Health, Bethesda, MD in 1997. Dr. Giannakakou became Assistant Professor of Hematology and Medical Oncology at the Winship Cancer institute of Emory University in 2000 and was recruited to WCMC in 2005. Dr. Giannakakou's research is focused on the biology of the microtubule cytoskeleton in cancer and the mechanism of action of antitumor drugs that target microtubules and are used in cancer chemotherapy. More specifically, her research tries to identify the intracellular trafficking and signaling pathways that require an intact and dynamic microtubule network as well as the little-understood functional consequences of drug-induced microtubule disruption and cell death. She is the co-leader of Project 2 in which she proposed to study the effects of microtubule dynamics in three dimentional cell migration and the cross talk between cancer-cell microtubules and the tumor microenvironment.
Michael King, Ph.D.
Michael King is an Associate Professor of Biomedical Engineering at Cornell University. King is an expert on the receptor-mediated adhesion of circulating cells, and has developed new computational and in vitro models to study the function of leukocytes, platelets, stem and cancer cells under flow. He is a former Whitaker Investigator, a James D. Watson Investigator of New York State, and an NSF CAREER Award recipient. King received the 2008 ICNMM Outstanding Researcher Award from the American Society of Mechanical Engineers, was the 2007-2008 Professor of the Year in Engineering at the University of Rochester, and received the 2009 Outstanding Contribution for a Publication in the International Journal Clinical Chemistry. He is the co-author of several books and over 50 journal articles. He is the leader of Project 3.
David M. Nanus, M.D., Ph.D.
David M. Nanus, MD is Professor of Medicine and of Urology; Mark W. Pasmantier Professor of Hematology and Oncology in Medicine; Chief of the Division of Hematology and Medical Oncology; and Director of the Genitourinary Oncology Research Laboratory in the Department of Medicine at Weill Cornell Medical College and New York Presbyterian Hospital, New York. He is recipient of numerous awards including membership in the American Society for Clinical Investigation and the American Association of Physicians.
Dr. Nanus is a physician scientist with a clear focus on increasing the understanding of genitourinary cancers, and developing that knowledge into novel treatment strategies. Dr. Nanus's current research focuses on investigating the mechanisms of sensitivity and resistance to targeted therapies in prostate and renal cancers, including using circulating tumor cells and animal models to achieve this goal. He is co-principle investigator on Project 3 "Adhesion of Tumor Cells in the Vascular Microenvironment".
Ari Melnick, Ph.D.
Dr. Melnick grew up in Argentina and received his medical degree at the University of Buenos Aires in 1990. He worked briefly as a laboratory technician with Dr. Luis Isola in the Hematology Division of the Mount Sinai School of Medicine. Dr. Melnick then pursued clinical training first in the Internal Medicine Residency Program and then in Hematology and Oncology at Mount Sinai. He then did a post-doctoral fellowship with Dr. Jonathan Licht at Mount Sinai in the area of transcriptional regulation in leukemias, and a visiting post-doctoral fellowship with Dr. Leonard Freedman at the Memorial Sloan Kettering Cancer Center in transcriptional regulation of chromatin.
He was the director of the Hematology-Oncology Fellowship program at Mount Sinai from 2000 to 2002.He started his own lab at the Albert Einstein College of Medicine in 2002, where he was the Belfer Faculty Scholar in Cancer Research.At Einstein he was also co-leader of the transcriptional activation and repression group, co-leader of the immuno-oncology program in the Albert Einstein Cancer Center, and co-leader of the Einstein Epigenomics Program.
He moved to the Weill Cornell Medical College in 2008 where he is now Associate Professor, Director of the Raymond and Beverly Sackler Center for Biomedical and Physical Sciences, Director of the Internal Medicine Research Residency, and Director of the WCMC Epigenomics Core Facility.
Dr. Melnick is a past ASH Faculty Scholar, Kimmel Foundation Scholar and is currently a Scholar of the Leukemia and Lymphoma Society.In addition to biomedical research, Dr. Melnick has a strong interest in mentoring and career development of physician scientist and scientific trainees.
Harold Craighead, Ph.D.
Harold Craighead received his Bachelor of Science Degree in Physics, with High Honors, from the University of Maryland, College Park in 1974. He received his Ph.D. in Physics from Cornell University in 1980. His thesis work involved an experimental study of the optical properties and solar energy applications of metal nanoparticle composites. From 1979 until 1984 he was a Member of Technical Staff in the Device Physics Research Department at Bell Laboratories. In 1984 he joined Bellcore where he formed and managed the Quantum Structures research group.
Dr. Craighead joined the faculty of Cornell University as a Professor in the School of Applied and Engineering Physics in 1989. From 1989 until 1995 he was Director of the National Nanofabrication Facility at Cornell University. Dr. Craighead was Director of the School of Applied and Engineering Physics from 1998 to 2000 and the founding Director of the Nanobiotechnology Center from 2000 to 2001. He served as Interim Dean of the College of Engineering from 2001 to 2002 after which he returned to the Nanobiotechnology Center as Director. He has been a pioneer in nanofabrication methods and the application of engineered nanosystems for research and device applications.
Dr. Craighead's recent research activity includes the use of nanofabricated devices for biological and biomedical applications. His research continues to involve the study and development of new methods for nanostructure formation, integrated fluidic/optical devices, nanoelectromechanical systems and single molecule analysis.
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Project 1 - Physiochemical Transducers and their Role in Tumor Angiogenesis
Project Leaders: Claudia Fischbach-Teschl (Cornell University) and Vivek Mittal (Weill Cornell Medical Center)
Tumors consist of distinct niches, and cellular crosstalk between these niches enhances tumor angiogenesis and metastasis via the recruitment of bone marrow elements. This project integrates tissue engineering, microfluidics, and mathematical modeling to recreate tumor-like niches and study the underlying extra- and intracellular signaling across multiple length scales. Studies in mouse models complement these physical sciences tools to assess the relevance of the identified signaling to bone marrow progenitor recruitment and metastasis.
Physiochemical Transducers and their Role in Tumor Angiogenesis
Endothelial cell-coated microchannel embedded within collagen scaffold.
Project 2 - Physical and Chemical Cues in Tumor Cell Migration
Project Leaders: Cynthia Reinhart-King (Cornell University) and Paraskevi Giannakakou (Weill Cornell Medical Center)
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)
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.
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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.
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Mike King Manuscript and Video published in JoVE
Brian Kirby and David Nanus Developments with CTCs
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