Publications

Most significant publications

My research program investigates the interface between the nervous and immune systems in health and disease. The immune system has long been known to impact nervous system function through neuroinflammatory pathways. Importantly and conversely, neural circuits have more recently been shown to control inflammatory responses through direct, structural interfaces between immune and nervous tissues. These cellular and molecular points of engagement are distributed across the body to serve important homeostatic and developmental functions. Their dysregulation, in turn, contribute to disease, including neurodevelopmental disorders.

Three primary avenues of my research program have made significant contributions to our growing understanding of the neuro-immune interface:

In this recent publication from my group on which I am a senior author, we characterized the regulation of danger-associated molecular patterns by the inflammasome executioner protein gasdermin D during pyroptosis. The field had postulated that like interleuin-1β, which is secreted through gasdermin D pores, intracellular danger molecules (e.g. HMGB1) would be released into the extracellular space to propagate inflammatory response by a similar mechanism. We discovered, in contrast, that HMGB1 release requires gasdermin D but that it does not permeate through its pore. Therefore, this work changed our understanding of how programmed cell death pathways trigger and propagate pro-inflammatory immune responses. These studies emphasize my laboratory’s experience and focus on inflammasome physiology and methodological expertise. We are now advancing these findings to better understand how pro-inflammatory programmed cell death pathways, such as gasdermin D-mediated pyroptosis, impact on neurodevelopment and neurodevelopmental diseases. Our preliminary investigations are revealing an important role for this pathway in the adverse structural and functional consequences of early life tissue injury as experienced by preterm neonates receiving NICU and operative care.

This seminal publication focuses on the interface between the immune and nervous systems to delineate how the nervous system monitors inflammation. Using electrical recordings, we demonstrated that sensory nerves are differentially activated by pro-inflammatory molecules (e.g. cytokines and bacterial products). Building on this discovery, we and others are establishing a compendium of cytokine-specific neural signatures to determine whether these unique signatures can be identified in neural recordings from preclinical models of systemic inflammatory disease or infection. This work has implications in the development of new bioelectronic assays and technologies for the diagnosis of neuroinflammatory diseases, responses to therapies, and prognostication.

In these publications, we identify and characterize a unique subset of immune cells that modulate systemic blood pressure and chronic viral infection in mice. Genetically abolishing these cells leads to hypertension, whereas their administration lowers blood pressure. In addition to establishing that immune cells impact the cardiovascular system, this work identifies a novel therapeutic target for the management of hypertension. This same subset of immune cells promotes vasodilation that enhances the migration of lymphocytes into tissue chronically infected with virus, thereby facilitating clearance of viral infections.

These and other projects in my laboratory are providing a new understanding of the fundamental interaction between the nervous and immune systems, including in neurodevelopment. We aim to translate our findings toward the treatment of preterm neonates at-risk of adverse neurodevelopmental outcomes and improve their lifelong brain health.

We provide the first evidence that a sensory nerve is activated by systemic inflammation in a mediator-specific fashion. This work lays the foundation for an immunological sensory neural code that may allow neural recordings to aid the clinical diagnosis and monitoring of inflammatory disease.

In these publications, we identify and characterize a unique subset of immune cells that modulate systemic blood pressure and chronic viral infection in mice. Genetically abolishing these cells leads to hypertension, whereas their administration lowers blood pressure.  In addition to establishing that immune cells impact the cardiovascular system, this work identifies a novel therapeutic target for the management of hypertension. This same subset of immune cells promotes vasodilation that enhances the migration of lymphocytes into tissue chronically infected with virus, thereby facilitating clearance of chronic viral infections.

Therapy for sepsis remains primarily supportive despite intense research into its pathogenesis.  Here, we highlight the importance of leaky vasculature and tissue edema in sepsis, and present the endothelium and barrier integrity as a new target for sepsis therapeutics, providing several potential treatment approaches.

Using multiple cell biological approaches, we deconstruct the ion fluxes within lysosomes that allow for their acidification, In addition to delineating a fundamental cell physiologic process, this work has significant implications on the pathogenesis of cystic fibrosis, particularly patient susceptibility to bacterial infections.

Peer-reviewed publications

 

  Journal Articles

Read more articles by Dr. Steinberg on Pubmed