Benjamin Steinberg

My research focuses on how the body’s nervous system monitors and controls inflammation. Direct cellular communication between neurons and immune cells allows the nervous system to modify how the immune system behaves in diseases such as sepsis, pain and heart failure. As we better understand the interaction between the nervous and immune systems, we can start to build therapeutics that target the nervous system to diagnose and treat inflammation-driven illnesses.

My laboratory works towards this translational objective in two ways: First, we study how powerful immune molecules (called cytokines) activate the body’s sensory nervous system in order to alert the brain to ongoing and potentially injurious inflammation. This project has implications in the development of new technologies for the diagnosis and monitoring of inflammatory diseases. Second, we are developing nerve stimulation paradigms that can modify the immune response in order to treat damaging inflammation. By targeting the nervous system, we will inform the develop of novel nervous system-based diagnostic tools and anti-inflammatory therapies.

Research Synopsis

My research focuses on the interface between the immune and nervous system, delineating how the nervous system monitors and modulates inflammatory responses. For example, activation of the vagus nerve suppresses systemic inflammation through a direct neuron-to-immune cell interaction termed the “inflammatory reflex”. My laboratory studies this prototypical neuro-immune communication with two primary objectives:

(1) Understand how peripheral neural circuits monitor systemic inflammatory responses. The sensory fibres of the vagus nerve are differentially activated by pro-inflammatory cytokines. My ongoing work aims to identify unique neural electrical signatures induced by immune molecules (e.g. cytokines) in inflammatory diseases. This work has implications in the development of new bioelectronic assays and technologies for the diagnosis of inflammatory diseases.

(2) Engineer electrical vagus nerve stimulation paradigms to treat inflammatory disease. Vagus nerve stimulation using empiric stimulation paradigms can decrease systemic inflammation through the “inflammatory reflex”. Using advances in nerve stimulation technology, we aim to design targeted electrical stimulation protocols that have anti-inflammatory effects. These electrical therapies represent a novel approach to the treatment of inflammation-driven diseases.

The conceptional and methodologic foundation to this work delineating therapeutically targetable neuro-immune communication has been published in leading journals such as Science, Nature Biotechnology, Anesthesiology, and the New England Journal of Medicine. Using the nervous system to monitor and modulate the immune system has the potential to impact on a variety of clinically important diseases in both adult and pediatric populations.

Recent Publications

1. Cox, M. A., Duncan, G. S., Lin, G. H. Y., Steinberg, B. E., Yu, L. X., Brenner, D., Buckler, L. N., Elia, A. J., Wakeham, A. C., Nieman, B., Dominguez-Brauer, C., Elford, A. R., Gill, K. T., Kubli, S. P., Haight, J., Berger, T., Ohashi, P. S., Tracey, K. J., Olofsson, P. S., & Mak, T. W. (2019). Choline acetyltransferase-expressing T cells are required to control chronic viral infection. Science (New York, N.Y.), 363(6427), 639–644. https://doi.org/10.1126/science.aau9072
2. Fergusson, D. A., Avey, M. T., Barron, C. C., Bocock, M., Biefer, K. E., Boet, S., Bourque, S. L., Conic, I., Chen, K., Dong, Y. Y., Fox, G. M., George, R. B., Goldenberg, N. M., Gragasin, F. S., Harsha, P., Hong, P. J., James, T. E., Larrigan, S. M., MacNeil, J. L., … Canadian Perioperative Anesthesia Clinical Trials Group. (2019). Reporting preclinical anesthesia study (REPEAT): Evaluating the quality of reporting in the preclinical anesthesiology literature. PloS One, 14(5), e0215221. https://doi.org/10.1371/journal.pone.0215221
3. Goldenberg, N. M., Hu, Y., Hu, X., Volchuk, A., Zhao, Y. D., Kucherenko, M. M., Knosalla, C., de Perrot, M., Tracey, K. J., Al-Abed, Y., Steinberg, B. E., & Kuebler, W. M. (2019). Therapeutic Targeting of High-Mobility Group Box-1 in Pulmonary Arterial Hypertension. American Journal of Respiratory and Critical Care Medicine, 199(12), 1566–1569. https://doi.org/10.1164/rccm.201808-1597LE
4. Goldenberg, N. M., Rabinovitch, M., & Steinberg, B. E. (2019). Inflammatory Basis of Pulmonary Arterial Hypertension: Implications for Perioperative and Critical Care Medicine. Anesthesiology, 131(4), 898–907. https://doi.org/10.1097/ALN.0000000000002740
5. Levin, D. N., Strantzas, S., & Steinberg, B. E. (2019). Intraoperative neuromonitoring in paediatric spinal surgery. BJA Education, 19(5), 165–171. https://doi.org/10.1016/j.bjae.2019.01.007
6. Masi, E. B., Valdés-Ferrer, S. I., & Steinberg, B. E. (2018). The vagus neurometabolic interface and clinical disease. International Journal of Obesity (2005), 42(6), 1101–1111. https://doi.org/10.1038/s41366-018-0086-1
7. Olofsson, P. S., Steinberg, B. E., Sobbi, R., Cox, M. A., Ahmed, M. N., Oswald, M., Szekeres, F., Hanes, W. M., Introini, A., Liu, S. F., Holodick, N. E., Rothstein, T. L., Lövdahl, C., Chavan, S. S., Yang, H., Pavlov, V. A., Broliden, K., Andersson, U., Diamond, B., … Tracey, K. J. (2016). Blood pressure regulation by CD4+ lymphocytes expressing choline acetyltransferase. Nature Biotechnology, 34(10), 1066–1071. https://doi.org/10.1038/nbt.3663
8. Steinberg, B. E. (2018). Neutrophils: A Therapeutic Target of Local Anesthetics? Anesthesiology, 128(6), 1060–1061. https://doi.org/10.1097/ALN.0000000000002205

Appointments

Staff Anesthesiologist, Department of Anesthesia and Pain Medicine, The Hospital for Sick Children
Scientist-Track Investigator, Program in Neuroscience and Mental Health, The Hospital for Sick Children
Assistant Professor, Department of Physiology, University of Toronto

Honours and Awards

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• Principal investigator. International Anesthesia Research Society Mentored Research Award (2019)
• Principal investigator. The Lung Association – Ontario Grant-in-Aid Program (2019)
• Canadian Society for Clinical Investigation (CSCI) / Canadian Institutes of Health Research (CIHR) Resident Research Award (2015)