Assistant Professor | Cardiovascular and Respiratory Platform

Neil Goldenberg

MD, PhD, FRCPC

Address

Program in Cell Biology, Hospital for Sick Children, Peter Gilgan Centre for Research and Learning, Room 19.9710, Toronto, Ontario Canada M5G 0A4

Research Interests

Research focuses on pulmonary vascular inflammation and vasoconstriction. Specific interests include mechanisms of immunological dysregulation in pulmonary arterial hypertension, including both innate immune activation and B cell dysfunction and autoimmunity.

Accepting

Fellows, Graduates, Summer Students

Research Synopsis

Research Interests: My work focuses on understanding the pathomechanisms underpinning pulmonary arterial hypertension. Beyond pure vasoconstriction, this is a disease of profound immune dysfunction, irreversible vascular remodeling, and metabolic change. Using an integrated platform consisting of patient-derived tissue, animal models, and primary cell culture, we seek to understand (a) how the environment present in pulmonary hypertension primes the immune system, and (b) how the immune system causes chronic vascular damage in order to manifest the disease. Specifically, we examine various modes of cell death (apoptosis, necrosis, pyroptosis) in the development of PH, and how such cell damage then activates both the innate and adaptive immune systems. We then investigate how this immunological milieu contributes to the physiology and vascular lesions seen in patients with PH. We hope to use this knowledge to design and test novel strategies for treating this devastating disease.

Keywords: Pulmonary hypertension, vascular inflammation, macrophage, B cells, autoimmunity, cytokines, necrosis, inflammasomes, connective tissue disease, scleroderma, congenital heart disease, antibodies, pulmonary inflammation, pulmonary histology, cardiac physiology, pulmonary physiology

Collaborators: Dr. Mark Friedberg, Dr. Benjamin Steinberg, Dr. Cynthia Guidos, Dr. Marc de Perrot, Dr. Susanna Mak

METHODS USED

Mouse and rat models (hypoxia, monocrotaline, sugen-hypoxia), primary lung cell culture, invasive hemodynamic measurements, echocardiography, histology and immunohistochemistry, immunofluorescence and live-cell imaging, ELISA, FACS, CyTOF (mass cytometry), protein biochemistry, PCR, functional cellular assays (migration, proliferation, differentiation).

EQUIPMENT USED

Hemodynamic measurements in vivo (ADInstruments), FACS, transthoracic echocardiography, Luminex ELISA, various protein biochemistry techniques, spinning-disc confocal microscopy

Recent Publications

Goldenberg NM, Rabinovitch M, Steinberg BE. The inflammatory basis of pulmonary arterial hypertension: Clinical implications. Anesthesiology. 2019 May 14.

Goldenberg NM, Hu Y, Hu X, Volchuk A, Zhao YD, Kucherenko MM, Knosalla C, de Perrot M, Tracey KJ, Al-Abed Y, Steinberg BE, Kuebler WM. Therapeutic targeting of high mobility group box-1 in pulmonary arterial hypertension. Am J Resp Crit Care Med. 2019 April 2.

Goldenberg NM and Steinberg BE. Inflammation drives pulmonary arterial hypertension. Anesthesiology. Online ahead of print, December 12, 2018.

Sugiyama MG, Raheel H, Mintsopoulos V, Goldenberg NM, et al. Lung ultrasound and microbubbles enhance aminoglycoside efficacy in the lung in E. coli-induced pneumonia and ARDS. Am J Resp Crit Care Med. April 2018.

Y, Zabini D, Gu W, Breitling S, Goldenberg NM, Kabir G, Connelly K, Kuebler WM. The role of the human immune system in chronic hypoxic pulmonary hypertension. Am J Resp Crit Care Med. April 2018.

Breitling S, Zhang H, Zabini D, Hu Y, Hoffmann J, Goldenberg NM, Buelow R, Kuebler WM. The mast cell - B-cell axis in lung vascular remodeling and pulmonary hypertension. Am J Physiol – Lung. 2017 May 1.

Appointments

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