Research Focus

Imagine, if we understood what the 30 trillions of cells in our body do at any given moment...

Now compare these 30 trillions of cells (not counting the microbiome!) to the earth population of 8B people (3,750 times more!). This creates a massive undertaking...

At CSB we develop innovative technologies to enable the discovery of new biology, drug targets and diagnostics.

Approach: we develop new integrated systems for subcellular analysis and use innovative imaging tools to decipher dynamic networks. This allows us to interrogate networks at multiple scales from populations to molecules.
New breakthrough for ultrafast bed-side cancer diagnosis

Rapid, automated, and point-of-care cellular diagnosis of cancer remains difficult in resource-limited settings due to lack of specialists and medical infrastructure. In a recent paper published in Science Translational Medicine, the biomedical engineering team at the Center for Systems Biology has developed an automated image cytometry system (CytoPAN) that allows rapid breast cancer diagnosis and receptor subtyping in 1 hour using as few as 50 cells obtained by fine needle aspiration (FNA). The combination of FNA and CytoPAN offers an alternative strategy for faster, minimally invasive cancer diagnosis in both developed and developing countries. Coupled with recently developed cycling technologies for FNA, this will also enable rapid molecular and cellular profiling of serial tumor samples in clinical trials. Learn more...

All metastases are not created equal

Metastases can form in locoregional lymph nodes – a form of progression that portends a worse prognosis but can still be curable – or they can develop in distant organs. Treatments for the latter case are typically considered palliative. It is unknown whether lymph node and distant metastases are only distinguished by their different prognostic implications, or whether the biology underlying their formation is also distinct. In a new study, published in Nature Genetics, the Naxerova lab at the Center for Systems Biology and collaborators at the Canary Center for Cancer Early Detection at Stanford now show that lymph node and distant metastases develop through different evolutionary mechanisms. Reconstructing the evolutionary histories of dozens of colorectal cancers, the team showed that lymph node metastases are a genetically highly diverse group. Their pronounced heterogeneity indicates that they can be seeded by many different primary tumor sub-lineages. In contrast, distant metastases are homogeneous. They typically resemble each other and have a recent common ancestor, suggesting that fewer primary tumor subclones possess the ability to form lesions in distant organs. These results show that the selective pressures shaping metastasis development in different anatomical sites differ substantially. Learn more...

Breaking bad habits in cancer therapy

Targeted cancer drugs are designed to kill tumor cells, but can elicit a tumor-protective wound-healing response as the body repairs its dying tissue. In a report published in Science Advances, a team at the MGH Center for Systems Biology and the Massachusetts Institute of Technology collaborated to understand mechanisms of how the immune response to kinase inhibitors could promote drug resistance often seen in patients. Using a computational pipeline to interpret multicellular signaling in the tumors of patients with melanoma or ovarian cancer, the team found that tumor cells adopted a program of wound healing especially related to the role of macrophages in clearing debris from dying cells. This signaling co-amplified between tumor cells and neighboring macrophages to cause drug resistance in a reinforcing feedback loop. To break this destructive cycle, the team formulated a nanotherapy that efficiently accumulated in the phagocytic macrophages of resistant tumors and delivered a toxic payload that blocked resistance. Learn more...