Neuroinflammation and Programmed Cell Death Pathways

The immune system and inflammation engage the nervous system across the lifespan to maintain a state of health. For example, cells in the nervous system can undergo a programmed cell death to repair tissues or fight against infection. These programmed cell death pathways include apoptosis and pyroptosis, which are essential component of healthy nervous system development. How these programmed cell death pathways are constrained within the nervous system to mitigate against injurious inflammation is unclear. Moreover, pathologies of the nervous system, such as pain, result in part through the dysregulation of the neuro-immune interface. We employ cell biological methods and models of disease to better understand the fundamental interaction between the nervous and immune systems, with a particular focus on programmed cell death pathways and pain across the lifespan. 

Specific research themes include:

1. Elucidation of novel immunologic therapeutic targets for neuropathic pain

Neuropathic pain is a disabling clinical condition that is often difficult to manage. It develops from dysfunction within the nervous system driven by immune activation. This theme investigates the fundamental interaction between the nervous and immune system in the pathogenesis of neuropathic pain to identify novel therapeutic targets.

2. Characterization of programmed cell death pathways in the nervous system

Programmed cell death pathways, such as pyroptosis, are important for normal development and health within the nervous system but can also contribute to neurological diseases. This theme investigates the fundamental cell biological processes that drive programmed cell death pathways and how these pathways contribute to health and disease within the nervous system.

Bioelectronic Medicine

This work is largely rooted in a new area of clinical and biomedical research termed bioelectronic medicine. Bioelectronic medicine aims to treat and diagnose disease and injury using medical device technologies that can read and write the electrical activity within the body’s nervous system. This combination of real-time diagnostic and therapeutic potential exploits the dense innervation of all the body’s tissues by the peripheral nervous system.  Nerve recording devices can be implanted on nerves to monitor and read neural activity. Decoding this activity may allow us to monitor patient physiology, diagnose disease and prognosticate. In turn, nerve stimulating or inhibiting devices have the potential to write or modulate specific nerve activity to change tissue function and restore health. We employ bioelectronic medicine approaches at the interface between the immune and nervous systems, utilizing the nervous system’s capacity to modulate immune reactions important to disease, particularly in perioperative and critical care.

Specific research themes include:

1. Delineation of how the nervous system monitors inflammation

We and others have shown that sensory nerves are differentially activated by pro-inflammatory molecules, called cytokines. Ongoing work aims to establish whether these cytokine-specific neural signatures can be identified in neural electrical recordings during systemic inflammation or infection. These findings have implications in the development of new bioelectronic assays for the diagnosis of inflammatory diseases, responses to therapies and prognostication.

2. Discovery of bioelectronic medicine therapies for pulmonary disease

A form of elevated blood pressure in the lungs, termed pulmonary arterial hypertension, is a devastating disease with a grim prognosis.  Its pathogenesis results from a dysregulated pulmonary and systemic immune response. As the nervous system can suppress inflammatory responses, this work aims to design novel bioelectronic medicine therapies that use the nervous system to restrain and treat the aberrant immune response that drives pulmonary arterial hypertension.