Measuring, Modeling, and Controlling Heterogeneity (M2CH) Center for Cancer Systems Biology

Summer 2019 internship announced!

Applications due February 15, 2019

In Summer 2019, the M2CH will host an undergraduate intern interested in solving complex problems in cancer through interdisciplinary research. The National Cancer Institute is offering a total of 16 internships at 15 locations, of which the M2CH program is a location that will accept one student from this program. If interested, read more at the National Cancer Institute website, select OHSU from their project list and apply following their instructions by February 15, 2019.

Introduction

The Measuring, Modeling and Controlling Heterogeneity (M2CH) Center is one of nine U54 Research Centers of the NCI Cancer Systems Biology Consortium (CSBC).The NCI is one of the 27 Institutes and Centers that comprise the National Institutes of Health.

Our overall goal at the M2CH Center for Cancer Systems Biology is to improve management of triple negative breast cancer (TNBC) by preventing cancer cells from developing resistance to chemotherapy. We are looking at how both intrinsic factors — such as DNA modifications, or epigenetic features of cancer cells — and extrinsic factors, specifically molecular signals in the immediate environment, or microenvironment of cancer cells — shape the ability of cancer cells to become resistant to cancer drugs.

M2CH projects figure

We learn how intrinsic and extrinsic factors influence differentiation state, proliferation and therapeutic response in TNBC through experimental manipulation and computational modeling of cancer cell lines, 3D engineered multicellular systems, xenografts and clinical specimens. We deploy single cell omic and imaging technologies that allow quantitative assessment of molecular, cellular, and structural heterogeneity. We interpret these data using computational models that define control networks and structures in heterogeneous systems as well as transitions between states of therapeutic resistance and sensitivity.
 
This is accomplished in three related projects:

  1. Project 1 focuses on measuring and managing resistance-associated heterogeneity intrinsic to cancer cells. 
  2. Project 2 focuses on identifying resistance-associated signals from the microenvironment and on mitigating effects from these signals on therapeutic response. 
  3. Project 3 applies spatial systems biology approaches to TNBC specimens and multicell type models thereof to discover molecular control networks that influence how cell intrinsic plasticity and microenvironment signaling alter therapeutic responses in complex tissues. All Projects analyze core cell lines, patient derived cultures, and FDA approved, pathway-targeted drugs (afatinib, ruxolotinib, trametinib, BYL719, cabozantinib, and everolimus).
Learn more about M2CH and each of its three projects at the Cancer Systems Biology Consortium site.

Inquiries

Please direct any inquiries regarding the Measuring, Modeling and Controlling Heterogeneity (M2CH) Center to .

Publications

Differentiation-state plasticity is a targetable resistance mechanism in basal-like breast cancer. Tyler Risom, Ellen M. Langer, Margaret P. Chapman, Juha Rantala, Andrew J. Fields, Christopher Boniface, Mariano J. Alvarez, Nicholas D. Kendsersky, Carl R. Pelz, Katherine Johnson-Camacho, Lacey E. Dobrolecki, Koei Chin, Anil J. Aswani, Nicholas J. Wang, Andrea Califano, Michael T. Lewis, Claire J. Tomlin, Paul T. Spellman, Andrew Adey, Joe W. Gray, and Rosalie C. Sears. Nature Communications. 2018 Sep 19;9(1):3815. doi: 10.1038/s41467-018-05729-w.