Benjamin Steinberg

Research Synopsis

My research focuses on the communication between the nervous and immune systems in inflammatory diseases, such as sepsis, pain and pulmonary arterial hypertension. The nervous system senses inflammatory molecules (bacterial products and cytokines) and modulate immune responses by reprogramming the inflammatory phenotype of immune cells. The inflammatory reflex mediated by the vagus nerve exemplifies this real-time modulation of immunity by the nervous system and forms the basis of our studies. Integrating preclinical animal models, in vivo electrophysiology and cell culture, we investigate how immune molecules, such as cytokines and bacterial products, activate sensory neurons. Once activated, the neurons transmit information regarding inflammation to the central nervous system. By decoding these electrical signals, we hope to “read” the neural immunologic code. Similarly, using pharmacologic and electrical nerve stimulation paradigms we examine how neuromodulation impacts on immunology in health and disease. Our aim is to “write” neural signals that modify immune responses. We apply these approaches to better understand the pathology underpinning pain and pulmonary vascular disease. This knowledge will inform the design and implementation of novel strategies that use neuromonitoring and neuromodulation to respectively evaluate and treated these devastating inflammatory diseases.

Keywords: Inflammation, neuroinflammation, neuromodulation, bioelectronic medicine, autonomic nervous system, pain, sepsis, pulmonary hypertension, cytokines, microglia, macrophages, inflammasomes, electrophysiology, pulmonary inflammation, pyroptosis

Detailed Description:
Extra-neural recordings from peripheral nerves in preclincal models of inflammation. These methods provide a detailed characterization of the real-time sensing of inflammation by the nervous system. In conjunction with behaviour and invasive physiologic measurements, these methods delineate how the nervous system senses and modulates immune responses and provide the substrate for designing neural strategies to monitor and treat inflammatory diseases.

Collaborators: Drs. Michael Salter, Neil Goldenberg, Mark Friedberg, Kevin Tracey, Yousef Al-Abed

METHODS USED

Preclinical models (spared nerve injury, nucleus pulposus, hypoxia, monocrotaline, sugen-hypoxia), animal behaviour, in vivo electrophysiology, hemodynamic measurements, echocardiography, primary immune and neuronal cell culture, histology and immunohistochemistry, immunofluorescence and live-cell imaging, protein biochemistry, ELISA, PCR

EQUIPMENT USED

Amplifier and stimulator (Intan Technologies), microcuff electrodes (CorTec), hemodynamic measurements (AD Instruments), transthoracic echocardiography, ELISA and FACS, protein biochemistry techniques, confocal and epifluorescent microscopy

Recent Publications

1. Goldenberg NM, Rabinovitch M & Steinberg BE. The inflammatory basis of pulmonary arterial hypertension. Anesthesiology. 2019; 131(4):898-907.

2. Levin DN, Strantzas S & Steinberg BE. Intra-operative neuro-monitoring in paediatric spinal surgery. British Journal of Anaesthesia Education. 2019; 19(5):165-171.

3. Goldenberg NM, Hu Y, Hu X, Volchuk A, Zhao YD, de Perrot M, Tracey KJ, Al-Abed Y, Steinberg BE* & Kuebler WM*. Therapeutic targeting of high mobility group box-1 in pulmonary arterial hypertension. American Journal of Respiratory and Critical Care Medicine. 2019; 199(12):1566-1569.

4. Goldenberg NM & Steinberg BE. Inflammation drives pulmonary arterial hypertension. Anesthesiology. 2019; 130(5):820-821.

5. Cox MA, Duncan GS, Lin GHY, Steinberg BE, Yu LX, Brenner D, Buckler LN, Elia AJ, Wakeham AC, Neiman B, Dominguez-Brauer C, Elford AR, Gill KT, Kubli SP, Haight J, Berger T, Ohashi PS, Tracey KJ, Olofsson PS & Mak TW. Choline acetyltransferase-expressing T cells are required to control chronic viral infection. Science. 2019; 363(6427):639-644.

6. Battinelli Masi E, Valdes-Ferrer SI & Steinberg BE. The vagus neruo-metabolic interface and clinical disease. International Journal of Obesity. 2018; 42(6):1101-1111.

7. Silverman HA, Stiegler A, Tsaava T, Newman J, Steinberg BE, Battinelli Masi E, Robbiati S, Bouton C, Huerta PT, Chavan SS & Tracey KJ. Standardization of methods to record vagus nerve activity in mice. Bioelectronic Medicine. 2018; 4:3.

Appointments

Cross-Appointed to Physiology
Primary: Anesthesiology
Staff anesthesiologist, Department of Anesthesia and Pain Medicine, The Hospital for Sick Children