Physical Sciences –
Oncology Center

The MIT PS-OC is collaboration among MIT, Harvard University, University of California San Francisco, Harvard Medical School, Boston University, Hubrecht Institute, and Brigham and Women's Hospital. It is one of twelve Physical Sciences in Oncology Centers awarded by the National Cancer Institute (NCI), part of the National Institutes of Health (NIH). The overarching goal of this team is to use both theoretical and experimental approaches inspired by Physics and Engineering to attack important problems in cancer biology by developing novel technology and analytical and computational methods to track the dynamics of cancer at the single cell level.

PS-OC assembles renowned investigators from cancer biology, experimental physics/engineering and theoretical/computational physics to address critical issues in cancer biology. These investigators 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 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.

Jump to: Projects | Cores | Investigators | Relevant Links 

More information about the PS-OC Network is available online:
Physical Sciences in Oncology | NCI Alliance for Nanotechnology in Cancer

Projects

Research in our center is focused on the following projects.

Project 1 - Single-Cell Transcript Counting of Stem Cell Differentiation and Reprogramming
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
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
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
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.

Cores

The PS-OC has two core facilities.

Core 1 - Single-Cell Transcript Counting Core
The Single-Cell Transcript Counting Core provides 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 Leader: Alexander van Oudenaarden (Massachusetts Institute of Technology)

Core 2 - Cell Sorting and Physical Measurement
This Core comprises novel technologies for measuring a wide range of physical properties of single cells, including mass, growth rate, density and deformability. These technologies are 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. Core Leader: Scott Manalis (Massachusetts Institute of Technology)

Investigators


Principal Investigator:
Scott Manalis, PhD
Associate Professor of Biological and Mechanical Engineering
Massachusetts Institute of Technology

Senior Scientific Investigator: Tyler Jacks, PhD
Director, Koch Institute for Integrative Cancer Research
David H. Koch Professor of Biology
Massachusetts Institute of Technology

Arup Chakraborty
Robert T. Haslam Professor of Chemical Engineering
Professor of Chemistry
Professor of Biological Engineering
Massachusetts Institute of Technology

Leonid Mirny
Associate Professor of Health Sciences and Technology and Physics
Massachusetts Institute of Technology

Jeroen Roose
Assistant Professor, Department of Anatomy
UC San Francisco

Relevant Links


Profile of Scott Manalis in Nature Methods
August 30, 2012

Seeing cancer in three dimensions
November 21, 2011

The impact of deleterious passenger mutations on cancer progression
November 20, 2011

New Insights into Pluripotent Stem Cell Development
December 3, 2009

Cancer research gets physical
October 27, 2009

van Oudenaarden Lab recent publications