Our current research focus is on uncovering the neuroimmune interactions in lung inflammation and host defense.
Neuronal regulation of respiratory infection and pneumonia
The respiratory tract is densely innervated by sensory and autonomic nerve fibers that are ideally well positioned at the respiratory tract's mucosal barrier surfaces to constantly interact and respond to pathogen invasion. Respiratory infections and pneumonia are major global health problems. Respiratory pathogens including viruses, bacteria or fungi cause deadly pneumonia due to extensive lung injury, immune dysfunction, and the development of acute respiratory distress syndrome (ARDS). Dysregulated inflammation, and rapid destruction of mucosal surfaces and barrier permeability are major hallmarks of ARDS. Our group is broadly interested to uncover how neurons regulate airway inflammation, lung immune cell responses and pulmonary defenses during respiratory infection and lethal pneumonia in mice. By leveraging the different tools from neuroscience, immunology and microbiology, we will try to understand the underlying mechanisms of airway barrier dysfunctions, and the role of immune and non-immune cell population in driving disease pathology during respiratory infection and ARDS.
Neuronal signaling pathways in intracellular antimicrobial defense
The nerve terminals at the respiratory tract release the neuronal mediators, including neuropeptides and neurotransmitters, at homeostasis and after a lung infection. Several respiratory pathogens are intracellular pathogens that exhibit intracellular lifestyle in the host cells for survival, multiplication, and infection progression. We hypothesize that neuropeptides and neurotransmitters actively crosstalk with both resident and recruited phagocytes in the lungs through their cognate receptors to modulate the intracellular antimicrobial functions of phagocytes, such as the production of reactive nitrogen species and reactive oxygen species. By using different pharmacological and genetic approaches to target the signaling molecules downstream of neuropeptides and neurotransmitters, we aim to identify the signaling pathways that regulate the antimicrobial functions of phagocytes to intracellular pathogens.
Neuroimmune crosstalk in chronic lung inflammation
Chronic lung inflammation is one the major characteristic features of several lung diseases such as chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis. Our knowledge on immunopathogenesis of chronic lung disease is very minimal. Cigarette smoke, a dominant factor for COPD development in human, can directly act on nerve terminals in the lung, and activate them to release the neuronal mediators such as calcitonin gene-related peptide and noradrenaline. Nerve fibers are highly abundant around the airways and are in close vicinity with airway-associated immune cells such as macrophages and innate lymphoid cells. We aim to uncover the interactions of the nervous system with resident immune cells in the lung that could regulate the pathologic inflammation and barrier defect in chronic lung disease.