Metastasis, the extracellular matrix 
and drug resistance

The main goal of our lab is to investigate the role of the tumor microenvironment, in particular the extracellular matrix, in driving metastasis and drug resistance using an interdisciplinary approach involving basic biology, bioengineering and translational research.

Haptotaxis 

We recently showed that gradients of the extracellular matrix protein fibronectin, present around blood vessels and the periphery of tumors, can attract certain tumor cells, leading to increased local invasion and ultimately metastasis. We are interested in understanding what other extracellular matrix cues drive directional migration. 

Intravital Imaging

In order to investigate mechanisms of migration in vivo, we use two-photon intravital imaging is a variety of mouse models. We have also developed novel techniques to study directional migration responses in vivo using this type of imaging. We are interested in developing this methods further coupled imaging windows to perform longitudinal imaging of tumor cell behavior and their responses to local cues. 

Directional migration in Cancer

Cancer cells must integrate multiple cues present within their tumor microenvironment to locally invade and ultimately metastasize. A goal of our research is to understand how multiple cues, soluble, substrate-bound or physical, cooperate to drive local invasion.

Drug resistance

For metastatic breast cancer, chemotherapy remains the standard of care. While the benefits of chemotherapy for the treatment of metastatic disease have been well documented, over 50% of triple-negative breast cancer patients become resistant to chemotherapy. Increasing our understanding of the mechanisms driving metastasis and drug resistance will help identify biomarkers that can be used to predict them, and characterize targetable signaling pathways to that can be used to prevent them. 

Collaborators

At MIT:
Richard Hynes, Koch Institute
Douglas Lauffenburger, Biological Engineering
Robert Langer, Koch Institute
Michael Cima, Koch Institute
Michael Hemann, Koch Institute

Outside MIT:
James Bear, UNC Chapel Hill, USA
Patricia Keely, University of Wisconsin Madison, USA