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.
A molecule that may help prevent Alzheimer’s disease

Communication within the glial cell ecosystem is essential for neuronal and brain health. We found, in humans and mice, that astrocyte-sourced interleukin-3 (IL-3) programs microglia to ameliorate the pathology of Alzheimer’s disease (AD). Upon recognition of β-amyloid (Aβ) deposits, microglia increase their expression of IL-3Rα—the specific receptor for IL-3—making them responsive to IL-3. Astrocytes constitutively produce IL-3, which elicits transcriptional, morphological, and functional programming of microglia to endow them with an acute immune response program, enhanced motility, and the capacity to cluster and clear aggregates of Aβ and tau. These changes restrict AD pathology and cognitive decline. Our findings identify IL-3 as a key mediator of astrocyte–microglia cross-talk and a node for therapeutic intervention in AD. Learn more...

Cancer: immunotherapies without side effects?

Immune checkpoint blockade (ICB) has revolutionized cancer therapeutics; however, in many cases, ICB is limited by immune-related adverse events (irAEs). Thus, a better understanding of the immune responses that lead to irAEs and how they are distinguished from antitumor immunity is needed. Here, Siwicki et al. used anti-CD40 therapy as a mediator of TH1-induced antitumor immunity in mouse tumor models. They found that liver-resident Kupffer cells induced neutrophil-mediated liver toxicity by producing IL-12 and responding to IFN-γ. Inhibition of the neutrophil response limited liver toxicity while retaining the antitumor efficacy of anti-CD40. Similar data were found in patients treated with anti–PD-1 and anti–CTLA-4. Together, these data suggest that the toxicity of ICB can be inhibited without negatively affecting antitumor immunity. Learn more...

Detecting and monitoring colorectal cancer in blood

In a new study published in Nature Biomedical Engineering, CSB investigators report a new high-throughput assay system for extracellular vesicles (EVs). Termed HiMEX (high-throughput integrated magneto-electrochemical extracellular vesicle), the system integrates EV enrichment and sensing in a single assay, and carries out parallel measurements in a 96-well plate format. Using plasma samples from patients with colorectal cancer (CRC) and healthy volunteers, the investigators identified a panel of EV biomarkers for CRC detection (96% accuracy). In a prospective cohort, EV profiles enabled assigning patients to a high- or a low-risk 5-year disease-free survival group, and monitoring tumor relapse during therapy. Learn more...