Decoding the Links Between Neurons and Disease

The peripheral nervous system (PNS) is the body's information superhighway, transmitting signals across our bodies much like fiber optic cables. Nerves are everywhere within us, permeating our tissues, enmeshing our cells in a web of neurites, and connecting distant parts of the body to each other. Without the PNS, our internal communications would break down.

Despite many advances in neuroscience, the intense focus on the biology of the brain has left the PNS by the wayside. Although we now have a deeper grasp of neural biochemistry, molecular biology, and electrophysiology, the PNS is still seen as a passive transmission pipeline for information heading to and from the brain.

Human prostate cancer biopsy sample image showing sympathetic nerves (in teal) and capillaries (in purple).

Our founder Flagship Pioneering asked:

What if, instead of being mere conduits of the central nervous system's commands, peripheral nerves are independent biological actors and even decision makers?

Image shows cancer cells (in gold) migrating aggressively along neurites (in teal), guided for motion.

It turns out, peripheral neurons are far from passive.

From cancer to gut inflammation and other areas of disease, nerves function in ways far beyond canonical contexts and mechanisms. The tissues they permeate make use of biochemical neural pathways and signals, and many non-neuronal cells communicate with and mimic nerves in disease settings.

This is a novel way of thinking about neural signaling as outside—or exo—traditional neurobiology, giving rise to the term exoneural biology to describe the field.

Image showing cancer cells (in gold) migrating along neurites (in teal).
Image showing tumor cells (in gold) driving neuronal sprouting (in teal).
Image showing nerves driving cancer (in gold) proliferation.
Image showing a macrophage (in magenta) migrating along neurites (in teal).

Cancer Cells Migrate Along Neurites

The migration of cancer cells along neurites is a mechanism by which tumors can metastasize (perineural invasion) to distant sites. Cygnal has developed assays that allow us to model, visualize, and quantitate this biology and identify factors that drive the process.

Tumors Drive Neuronal Sprouting

Cancer cells (in vitro) and tumors (in vivo) have a striking ability to promote the sprouting or axonogenesis of neurons. We have developed assays that allow us to survey this biology across multiple tumor types using visualization and quantitation efforts.

Nerves Drive Cancer Proliferation

The interaction between neurons and cancer cells is bi-directional. Cygnal has developed assays that allow the quantitation of cancer cell growth in response to the presence of soluble and contact-dependent factors derived from neurons that signal to cancer cells.

Neurons Regulate Cytokine Expression from Macrophages

Neuron to immune cell communication is a key regulator of the immune response. Cygnal is studying the effects of this cross-talk on the production of cytokines by macrophages (and other immune cells) using in vitro assays which are subsequently translated to in vivo application.

Cygnal speaks the language of neurons.