Massachusetts Institute of Technology Physical Sciences-Oncology Center
Massachusetts Institute of Technology, Cambridge, MA
Center Summary:
Massachusetts Institute of Technology Physical Sciences-Oncology Center (MIT PS-OC) will assemble renowned investigators from cancer biology, experimental physics/engineering and theoretical/computational physics to address critical issues in cancer biology. These investigators will employ experimental and theoretical approaches to construct innovative technology and analytical and computational tools to explore the process of carcinogenesis at the single cell level. This group theorizes that the intersection of these varied disciplines will yield major breakthroughs in the principles of cancer formation. These investigators will utilize pioneering single-cell mRNA counting techniques to model stem cell differentiation and reprogramming signaling networks as well as to probe the connection between cell growth and the cell cycle. Gene expression of various transcripts in individual cells will be surveyed over time to measure the quantity and pattern during these processes. Likewise, Ras-regulated signaling networks and neoplastic progression will be explored and used to establish computational models. Overall, these studies will provide a better understanding of the complexity of cancer and should facilitate the discovery of novel therapeutic targets.
| Website: http://web.mit.edu/ki/research/centers/psoc.html |
| Collaborators: |
Boston University
Brigham and Women's Hospital
Broad Institute
Harvard Medical School
Hubrecht Institute
Stanford University
University of California-San Francisco
Whitehead Institute |
Project 1 - Single-Cell Transcript Counting of Stem Cell Differentiation and Reprogramming
Project Leader: Alexander van Oudenaarden (Massachusetts Institute of Technology)
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The general objective of this project, led by Dr. Alexander van Oudenaarden, is to develop quantitative models of stem cell differentiation and reprogramming by obtaining absolute measurements of the transcript abundance in individual stem cells and their progeny in healthy tissue and cancer. Two complementary experimental systems will be explored: the intestinal epithelium and induced pluripotent stem cells.
Project 2 - Complementary in silico, in vitro, and in vivo Studies to Deconvolute Ras Signaling Networks in T Cell Lymphoma
Project Leader: Arup Chakraborty (Massachusetts Institute of Technology)
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The central theme of this project, led by Dr. Arup Chakraborty, is to employ complementary theoretical and experimental studies at the crossroads of the physical and life sciences to deconvolute the origins of aberrant Ras signaling in the context of a specific T cell lymphoma observed in the clinic. We will especially try to understand the mechanisms underlying our recent observation of complex and heterogeneous responses.
Project 3 - Coordination of Cell Growth and Division in Normal and Cancer Cells
Project Leader: Scott Manalis (Massachusetts Institute of Technology)
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The replication and segregation of the genome (the cell cycle) and the increase in bio-mass of individual cells (cell growth) must be coordinated in all cells. Many tumor suppressors and oncogenes can alter the normal balance between growth and division and some cancers are characterized by abnormal cell size. The goal of this project, led by Dr. Scott Manalis, is to deconvolve cell growth and the cell division cycle, determine the molecular basis for the coordination of these two processes, and determine how these two processes and their coordination are altered in cancer.
Project 4 - Modeling Neoplastic Progression and Analyzing Genomic Data to Characterize the Load of Driver and Passenger Mutations in Cancer
Project Leader: Leonid Mirny (Massachusetts Institute of Technology)
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The development of cancer can be considered as an evolutionary process within an organism. During neoplastic progression, cells acquire mutations, compete for resources, and are subject of selection for ability to grow fast in a complex and dynamic environment. The goal of the project, led by Dr. Leonid Mirny, is to develop a theory of neoplastic evolution informed by cancer genomic and experimental data; use it as a framework for characterization of driver and passenger mutations by original statistical techniques, and to test feasibility of pushing a cancer into a population meltdown due to elevated mutation load.
Core 1 - Single-Cell Transcript Counting Core
Core Leader: Alexander van Oudenaarden (Massachusetts Institute of Technology)
The Single-Cell Transcript Counting Core will provide the investigators of the MIT PS-OC and investigators of other PS-OCs in the network with the infrastructure to image individual mRNA molecules in single cells, both in culture and in tissue. In addition to the exceptional sensitivity and spatial resolution, superior to other existing mRNA imaging methods, this technique allows measurements of absolute quantities of up to three different mRNAs in a single cell.
Core 2 - Cell Sorting and Physical Measurement
Core Leader: Scott Manalis (Massachusetts Institute of Technology)
This Core comprises two novel technologies that are currently in development: i) The cell sorting system which consists of microfluidic technology developed by Innovative Micro Technology (IMT) that utilizes fluorescence activated sorting, and ii) The single cell measurement platform is based on the suspended microchannel resonant (SMR) mass sensor, which is capable of measuring the buoyant mass and growth rate of single cells with high precision. IMT is currently in the process of establishing a new generation of cell sorting microchips that have been designed to reduce clogging and sensitivity limitations of the previous generation. The SMR mass sensing technology is available at this time for measuring the mass and growth rates of mammalian cells in suspension and in the future will be equipped with simultaneous fluorescence readout so that four parameters: mass, growth rate, the intensity of fluorescent markers, and the rate of change of fluorescent intensity can all be correlated from individual living cells.
Alexander van Oudenaarden, Ph.D.
Dr. Alexander van Oudenaarden is a Professor of Physics and Biology at MIT. His research focuses on how single cells use gene and protein networks to accurately process intra- and extracellular signals. His laboratory made pioneering contributions to understanding stochastic gene expression and systems biology at the single-cell level. The current efforts in the van Oudenaarden group are focused on an integrated theoretical and experimental approach to understand the role of stochastic gene expression during development and differentiation. This includes the development of novel methodology to quantitatively monitor expression in single cells and the application of theoretical concepts from control theory, linear systems theory, and statistical physics to biological problems. He obtained his Ph.D. degree in 1998 (with highest honors) and received the 'Andries Miedema' Award for best Ph.D.-research in the field of condensed matter physics in the Netherlands. From 1998 to 1999, he was a postdoctoral fellow at Stanford University. He joined the MIT faculty in 2000. In 2001, he was named an Alfred Sloan Research Fellow, a Keck Career Development Professor in Biomedical Engineering, and received the NSF CAREER award. He was promoted to Associate Professor with tenure in 2004. Since 2001 he has been teaching a Graduate level course in Systems Biology at MIT for which he received the School of Science Prize for Excellence in Graduate Teaching in 2007. In 2008 Dr. van Oudenaarden was promoted to full Professor of Physics at MIT and received a John Simon Guggenheim Fellowship and the NIH Director’s Pioneer Award.
Tyler Jacks, Ph.D.
Dr. Tyler Jacks is the David H. Koch Professor of Biology and the Director of the Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology. He is also an Investigator of the Howard Hughes Medical Institute. Dr. Jacks received his B.A. in Biology from Harvard College in 1983. His Ph.D. thesis was performed with Harold Varmus at the University of California, San Francisco. He was a post-doctoral fellow with Robert Weinberg at the Whitehead Institute at MIT. Dr. Jacks joined the faculty at MIT in 1992. He has pioneered the use of gene targeting technology in the mouse to study cancer-associated genes and to construct mouse models of many human cancer types, including cancers of the lung, brain and ovary. His laboratory has made seminal contributions to the understanding of the effects of mutations of several common cancer-associated genes. This research has led to novel insights into tumor development, normal development and other cellular processes. In addition to mouse modeling, a major focus of research in Dr. Jacks’ laboratory has been the role of p53 in the elimination of damaged and pre-cancerous cells by programmed cell death, a form of cellular suicide. He has published more than 200 scientific papers. Dr. Jacks has served on the Board of Scientific Advisors of the National Cancer Institute (NCI) and the Board of Directors of the American Association of Cancer Research (AACR); he is currently President of the AACR and was elected to the National Academy of Sciences in 2009.
