National Cancer Institute
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University of Southern California

Los Angeles, CA

Overview | Investigators | Projects | Cores

University of Southern California

Overview

Center Summary

The University of Southern California Physical Sciences-Oncology Center's (USC PS-OC) overall goal is to thoroughly understand therapeutic response. Investigators will establish a predictive model of cancer that they can utilize to determine tumor steady state growth and drug response, particularly those involved in the hematological malignancies of acute myeloid leukemia and non-Hodgkin lymphoma. Furthermore, multi-scale physical measurements will be unified with sophisticated modeling approaches to facilitate the development of a model that can derive the tumor’s traits during its growth and after any distress, such as chemotherapeutic treatment. These investigators will apply pioneering measurement platforms to resolve real-time protein interactions and protein abundance and to characterize protein modifications. Appropriately, these studies will also address tumor and host response to therapy using a systems approach. Overall, the predictive tumor response model should enable clinicians to determine the most efficacious therapies a priori and reduce deleterious side effects.

Principal Investigator: W. Daniel Hillis, Ph.D.

Senior Scientific Investigator: David B. Agus, M.D.

Website: http://www.uscpsoc.org/

Collaborators: Arizona State University, Memorial Sloan Kettering, New York University, Northeastern University, Stanford University, University of California, Los Angeles, University of Louisville, University of New Mexico

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Investigators

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W. Daniel Hillis, Ph.D., Principal Investigator
W. Daniel Hillis is Judge Widney professor of engineering and medicine of the University of Southern California (USC), and Chairman and Chief Technology Officer of Applied Minds, a research and development company creating a range of new products and services in software, entertainment, electronics, biotechnology and mechanical design. Previously, Hillis was Vice President, Research and Development at Walt Disney Imagineering, and Disney Fellow. He developed new technologies and business strategies for Disney’s theme parks, television, motion pictures, Internet and consumer products businesses. Hillis was co-founder of Thinking Machines Corp., a leading innovator in massive parallel supercomputers and RAID disk arrays. In addition to conceiving and designing the company’s major products, he worked closely with customers in applying parallel computers to problems in astrophysics, aircraft design, financial analysis, genetics, computer graphics, medical imaging, image understanding, neurobiology, materials science, cryptography and subatomic physics.Hillis is an inventor, scientist, author, and engineer. He holds over 200 U.S. patents, and is the designer of a 10,000-year mechanical clock. Hillis has published scientific papers in journals such as Science, Nature, Modern Biology, Communications of the ACM and International Journal of Theoretical Physics and is an editor of several other scientific journals, including Artificial Life, Complexity, Complex Systems, Future Generation Computer Systems and Applied Mathematics. He is a Member of the National Academy of Engineering, a Fellow of the Association of Computing Machinery, a Fellow of the International Leadership Forum, and a Fellow of the American Academy of Arts and Sciences.

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David B. Agus, M.D., Senior Scientific Investigator
Dr. David B. Agus is a professor of medicine and engineering at the University of Southern California Keck School of Medicine and Viterbi School of Engineering and heads U.S.C.’s Westside Cancer Center and the Center for Applied Molecular Medicine. He is one of the world’s leading cancer doctors, and the co-founder of two pioneering personalized medicine companies, Navigenics and Applied Proteomics. Dr. Agus is an international leader in new technologies and approaches for personalized healthcare and chairs the Global Agenda Council on Genetics for the World Economic Forum. He has received numerous awards, including the 2009 Geoffrey Beene Foundation’s Rockstar of Science Award.   Dr. Agus’ first book called “The End of Illness” was published in January, 2012 by the Free Press Division of Simon & Schuster and is a New York Times #1 best seller.

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Garry Nolan, Stanford University, Project 1 Leader
Garry Nolan is a Professor in Microbiology and Immunology at Stanford University. Dr. Nolan's areas of expertise include signaling biology, immunology, cancer biology, retroviral design, bioinformatics, and genetics. His laboratory's recent interests include studying signaling alterations at the single cell level in leukemia and lymphomas, cancer stem cells, and determining which of these signaling attributes correlate with patient outcome, drug reactivity, and mechanism of disease progressions. Similarly, he works on global representations of signaling attributes and capabilities in the immune system in autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. He develops and applys advanced tools in informatics, such as machine learning, as implemented specifically for single cell analysis and use of perturbation analysis. In addition, he has an extensive program in the development of hardware algorithm implementations (using both field programmable gate arrays as well as graphical processing units) for highly parallelized machine learning of network structures.

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Parag Mallick, Stanford University, Project 1 Leader
Parag Mallick graduated from Washington University in St. Louis with a BS in Computer Science. He then obtained his Ph.D. from UCLA in Chemistry & Biochemistry, where he worked with Dr. David Eisenberg. At UCLA he received both an NSF IGERT Fellowship and an NSF Biotechnology fellowship. He completed Post-Doctoral studies at The Institute for Systems Biology, in Seattle, WA with Dr. Ruedi Aebersold. He is now faculty with the Canary Center for Cancer Early Detection at Stanford University and Center for Applied Molecular Medicine at USC, where he is developing quantitative multi-scale to better prioritize potential biomarker candidates and to accurately describe cellular regulation and dysregulation. In addition, he is the principle investigator of ProteoWizard, an open-source platform for accelerating the development of tools to analyze Proteomics Data.

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Matteo Pellegrini, University of California Los Angeles, Project 2 Leader
Matteo Pellegrini is a biophysicist who has served on the UCLA Life Sciences Division faculty since he joined the Department of Molecular, Cell and Developmental Biology in 2005. Dr. Pellegrini earned his B.A. in Physics at Columbia University and his Ph.D. in Physics at Stanford. He was a postdoctoral fellow at UCLA, where he worked on computational biology. Following his postdoctoral studies, Dr. Pellegrini co-founded a start-up company and later worked for the pharmaceutical company Merck before returning to UCLA. His laboratory research centers on the development of novel computational approaches to analyze genomic data. The Pellegrini group was instrumental in the development of whole genome bisulfite sequencing to measure the methylation status of nearly every cytosine in the genome. His present focus is on data produced using the latest generation of high throughput sequencers. Today the Pellegrini group is developing suites of tools for the analysis of high throughput sequencing data such as methC-seq, RNA-seq and ChIP-seq. His is currently mentoring half a dozen graduate students, and one of these has recently obtained his PhD. He has also advised multiple postdocs, one of which has recently moved on to a faculty position.

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Sanjiv Gambhir, Stanford University, Project 3 Leader
Sam Gambhir's laboratory is focused on the molecular imaging of living subjects with a particular emphasis on cancer imaging. Dr. Gambhir has developed numerous molecular imaging assays to interrogate fundamental cell/molecular events including cell viability, cell trafficking, gene expression, protein levels, and protein-protein interactions. Several of his lab's assays have been clinically translated. He has also been developing multimodality molecular imaging strategies that utilize the strengths of optical, photoacoustic, as well as radionuclide based imaging. He has expertise in developing molecular imaging agents including small molecule, engineered proteins, and nanoparticle based agents. He also has expertise in testing and optimizing these agents in small animal models. Finally, he is able to translate these agents for clinical diagnostics and management of cancer. Dr. Gambhir has significant expertise in working with large teams of scientists as PI of both the NCI ICMIC P50 and NCI CCNE U54.

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Vittorio Cristini, University of New Mexico, Project 3 Leader
Vittorio Cristini, PhD, the Victor & Ruby Hansen Surface Professor of Pathology, Chemical and Biomedical Engineering at the University of New Mexico, is a leading expert and researcher in the fields of mathematical and computational biology, applied and computational mathematics, mathematical oncology, complex fluids and microfluidics, and multidisciplinary (bio)materials science. He serves as editor for Cancer Research and several biomedical journals, and has published one book with Cambridge University Press, numerous book chapters and more than 70 journal articles, with an h-factor of 30. Among a number of awards, Dr. Cristini received the 2000 "Andreas Acrivos Dissertation Award in Fluid Dynamics" by the American Physical Society. His Bulletin of Mathematical Biology 2005 paper has been designated as a "New Hot Paper in the field of Mathematics" by the ISI Web of Knowledge, being in the top 0.1 percentile of citations; two articles have been featured in the Cancer Research Highlights of the American Association for Cancer Research. Cristini's research has been supported by the Cullen Trust for Health Care, the National Science Foundation, the National Cancer Institute, the Department of Defense, the State of California, the State of Texas, and the State of New Mexico among others. In addition to his position at the University of New Mexico, Dr. Cristini has been appointed as SULSA professor by the Scottish Universities Life Sciences Alliance and as honorary professor of mathematics by the University of Dundee, Scotland. Dr. Cristini has continuously collaborated with Dr. Agus, Mallick and coworkers since 2008 resulting in peer reviewed joint publications and funding. Because of his vast experience in modeling tumor growth and response to drug treatment, Dr. Cristini has ideal background and expertise to lead the computational projects on lymphoma growth and chemotherapy as part of Research Project 3 of the USC PS-OC.

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Josh LaBaer, Arizona State University, Project 4 Leader
Joshua LaBaer, M.D., Ph.D., formerly the Director of the Harvard Institute of Proteomics (HIP), is the Piper Chair in Personalized Medicine, Director of the Virginia G. Piper Center for Personalized Diagnostics and the Chair of the Directorate of the Biodesign Institute. His efforts involve leveraging the Center's formidable resources for the discovery and validation of biomarkers—unique molecular fingerprints of disease—which can provide early warning for those at risk of major illnesses, including cancer and diabetes. He completed medical and graduate school at the University of California, San Francisco where he studied steroid regulation of DNA transcription and protein-DNA interactions. He completed his internship and residency at the Brigham and Women's Hospital and a clinical fellowship in Oncology at the Dana-Farber Cancer Institute in Boston. Dr. LaBaer is a member of the National Cancer Institute Board of Scientific Advisors. Recently he was elected Chair of the EDRN Executive Committee and Co-Chair of the Steering Committee. Dr. LaBaer serves as an associate editor of the Journal of Proteome Research, and a member of the editorial boards of Analytical Chemistry, Current Opinion in Biotechnology, Cancer Biomarker, Molecular Biosystems, and Clinical Proteomics. He is treasurer and president-elect for US Human Proteome Organization (USHUPO) and a member of the Scientific Advisory Committee for Plexera.

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Shan Wang, Stanford University, Project 4 Leader
Dr. Wang currently serves as the director of the Stanford Center for Magnetic Nanotechnology and a Professor of Materials Science & Engineering, jointly of Electrical Engineering at Stanford University, and by courtesy, a Professor of Radiology at Stanford School of Medicine. He is a Co-PI of the Stanford-led Center for Cancer Nanotechnology Excellence and Translation (CCNE-T). He is also with the Geballe Laboratory for Advanced Materials, and is affiliated with Nanoelectronics Research Initiative (NRI), Stanford Bio-X Program, Cancer Institute and Cardiovascular Institute. His research interests lie in magnetic nanotechnologies and information storage in general and include magnetic biochips, in vitro diagnostics, cell sorting, magnetic nanoparticles, nano-patterning, spin electronic materials and sensors, magnetic inductive heads, as well as magnetic integrated inductors and transformers. He has published over 190 papers, and holds 28 patents (issued and pending) on these subjects. Dr. Wang contributed two books and four book chapters on magnetic biochip, nanoparticles, information storage, and embedded inductors, respectively, and gave more than 100 invited presentations in major scientific conferences and seminars around the globe, and his work received media coverage from ABC TV, Economist, San Jose Mercury News, Technology Review, EE Times, ScienceWatch, People's Daily and the like. Dr. Wang was an inaugural Frederick Terman Faculty Fellow at Stanford University (94-97), an IEEE Magnetics Society Distinguished Lecturer (2001-2002), and was elected an IEEE Fellow (2009). He also received, the Gates Foundation Grand Challenge Explorations Award (2010), the Obducat Prize (2007-8), a National Academies Keck Futures Initiative Award (2006), an IBM Partnership Award (1999), and was selected to the CUSPEA program organized by Nobel Laureate T. D. Lee in 1986. His students have won BMEidea Competition 1st Prize, IEEE President's Change the World Competition 1st Prize (2009), and IEDM Best Student Paper award (2006). Prof. Wang received the B.S. degree in physics from the University of Science and Technology of China in 1986, the M.S. in physics from Iowa State University in 1988, and the Ph.D. in electrical and computer engineering from the Carnegie Mellon University (CMU) at Pittsburgh in 1993.

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Mitchell E. Gross, University of Southern California, Core 1 Leader
Dr. Gross is the Research Director of the USC Westside Cancer Center and the Center for Applied Molecular Medicine and Associate Professor of Medicine and Urology at the Keck School of Medicine, University of Southern California. His research interest focuses on applying modern techniques relating to the study of genes and proteins (genomics and proteomics) on the clinical problems faced in treating cancer patients. A particular interest is to understand and apply new findings and therapies related to the androgen receptor (male hormones) and related proteins and pathways as treatment for prostate cancer. As a medical oncologist, his clinical activities are focused on clinical trials incorporating both molecularly targeted and conventional therapies to the care of cancer patients. Dr. Gross has earned degrees from the University of California, San Diego (B.A.), Baylor College of Medicine in Houston (M.D.), and the University of California, Los Angeles (Ph.D. Molecular Biology). He completed a residency in internal medicine and a fellowship in hematology and medical oncology at the UCLA Center for the Health Sciences. Among the many academic honors awarded to Dr. Gross, he is particularly distinguished with membership in the Phi Beta Kappa and Alpha Omega Alpha honor societies. His research has been published in major biomedical research journals including Blood, Proceedings of the National Academies of Science, Oncogene, Clinical Cancer Research, among others.

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Carl Kesselman, University of Southern California, Core 2 Leader
Dr. Carl Kesselman is Professor of Industrial and Systems Engineering and a Fellow in the Information Sciences Institute (ISI) in the Viterbi School of Engineering at the University of Southern California and is also a Professor of Preventive Medline at the Keck School of Medicine at USC. He is the Director of the Medical Information Systems Division at ISI, the Director of the Center for Biomedical Informatics Systems and serves as PI of the NIH funded Biomedical Research Informatics Network (BIRN). He received a Ph.D. in Computer Science from the University of California, Los Angeles, a Master of Science degree in Electrical Engineering from the University of Southern California, and Bachelors degrees in Electrical Engineering and Computer Science from the University at Buffalo. Dr. Kesselman's current research interests include health informatics as well as all aspects of Grid computing, including basic infrastructure, security, resource management, high-level services and Grid applications. He is the author of many significant papers in the field. Together with Dr. Ian Foster, he initiated the Globus Project™, one of the leading Grid research projects. The Globus project has developed the Globus Toolkit®, the de facto standard for Grid computing. Dr. Kesselman received the 1997 Global Information Infrastructure Next Generation Internet award, the 2002 R&D 100 award, the 2002 R&D Editors choice award, the Federal Laboratory Consortium (FLC) Award for Excellence in Technology Transfer and the 2002 Ada Lovelace Medal from the British Computing Society for significant contributions to information technology. Along with his colleagues Ian Foster and Steve Tuecke, he was named one of the top 10 innovators of 2002 by InfoWorld Magazine. In 2003, he and Dr. Foster were named by MIT Technology Review as the creators of one of the "10 technologies that will change the world." In 2006 Dr. Kesselman received an Honorary Doctorate from the University of Amsterdam. In 2007, he received the Internet2 Idea award, and the ComputerWorld Horizon Award.

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Projects

Project 1 – Dynamic State Space Modeling of Cancer Cell Response to Therapy

Project Leaders: Garry Nolan (Stanford University) and Parag Mallick (University of Southern California)

Research Project 1 attempts to develop models of how cells react to changes in their genetic makeup and their local environment.  These models will be used to understand the mechanisms by which cells respond to, or are resistant to therapeutic interventions.

Project 1  Dynamic State Space Modeling of Cancer Cell Response to Therapy

Project 2 – A Cancer Evolution Space-Time Machine

Project Leader: Matteo Pellegrini (University of California, Los Angeles)

The development of drug resistance in tumor cells significantly limits the outcome of contemporary therapies.  To address this limitation we will investigate at a genetic, epigenetic, transcriptomic and metabolic level how the resistant cells differ from the original population using next-generation sequencing and mass spectrometry, and thus suggest secondary targets for therapeutics that might increase the cytotoxic efficiency of drugs.

Project 3 – Multi-Scale Cancer Modeling: From Cell Phenotypes to Cancer Spread and Response to Therapy

Project Leaders: Vittorio Cristini (University of Texas Health Science Center - Houston) and Sanjiv Gambhir (Stanford University)

This project studies the growth and response to treatment of lymphoma tumors by combining advanced imaging, mathematical and computational modeling techniques.  The goal is to predict the response of lymphomas to chemotherapy by taking into account the transport of substances within tumors as well as the physical mechanisms that may influence the tumor growth and recurrence after treatment.

Intravital Microscopy of neovasculature (red) and tumor cells (green)
Intravital Microscopy of neovasculature (red) and tumor cells (green)

3D simulation of neovasculature (dark red) and tumor (shades of purple)
3D simulation of neovasculature (dark red) and tumor (shades of purple)

Project 4 - Integrated Multi-scale analysis of Tumor and Host Response to Therapy

Project Leaders: Shan Wang (Stanford University) and Josh LaBaer, M.D., Ph.D. (Arizona State University)

Many factors contribute to treatment failure in cancer including lack of tumor response to the drugs, toxicity to the host, tumor growth in sanctuary sites, and the emergence of resistance to drugs. Typically, these factors are studied individually, but it is their action in concert that ultimately overwhelms the patient. RP4 is dedicated to multi-scale measurements of the host response to cancer and its therapy and integrating this information with the tumor responses measured by the other projects into a comprehensive, predictive functional interaction tumor-host (TH) model. This model will be grounded on a novel data set of two key mechanisms mediating TH interactions: 1) host immune response and 2) cytokines that mediate intercellular communication. Emerging technologies such as nucleic acid programmable protein array (NAPPA) and magneto-nanosensors are being developed to follow cancer therapy responses in animal models relevant to lymphoma, acute myeloid leukemia (AML), and lung cancer.

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Cores

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Core 1 - Biomaterials Dissemination

Core Leader: Mitchell Gross (University of Southern California)

The primary aim of this Core is to provide the basic biologic specimens that will inform the modeling approaches across multiple parts of this proposal. The Aims include: Standardizing sample processing and storage within this PS-OC and providing high-quality and uniform samples for coordinated analysis.

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Core 2 - Data and Computational Models Dissemination

Core Leader: Carl Kesselman (University of Southern California)

The primary aim of this Core is to provide the information technology infrastructure needed to enable sharing of the heterogeneous data produced by the various research projects allowing these data to be integrated into multi-scale models. This Core will additionally coordinate model archiving and sharing.

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