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

What is the M2CH?

The Measuring, Modeling and Controlling Heterogeneity Center for Cancer Systems Biology (M2CH-CCSB, or simply M2CH), is one of thirteen "U54 Research Centers" which are part of the Research Network of the National Cancer Institute Cancer Systems Biology Consortium.

Goal is to improve management of triple negative breast cancer

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

A schematic of the overall project aims of the M2CH

A cancer system biology approach to breast cancer

We learn how intrinsic and extrinsic factors influence differentiation state, proliferation and therapeutic response in triple negative breast cancer 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:

  • Project 1 focuses on measuring and managing resistance-associated heterogeneity intrinsic to cancer cells. 
  • Project 2 focuses on identifying resistance-associated signals from the microenvironment and on mitigating effects from these signals on therapeutic response. 
  • Project 3 applies spatial systems biology approaches to triple negative breast cancer 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 Heidi Feiler, Scientific Program Manager, feiler@ohsu.edu.

Publications