After practicing medicine for a few years as a pediatrician and then an anesthesiologist in China, I realized I was a researcher trapped inside a physician’s body. I went on to obtain my doctorate in myocardium physiology and biochemistry at Oxford University, and became a research faculty at GWU. With the support of two American Heart Association grants, I studied the effect of anesthetics and opioids in the cardiac parasympathetic vagal neurons in my early career, producing eleven publications.
During the past ten years the focus of my research had shifted to the neural pathways that orchestrate complex disorders such as heart failure, obstructive sleep apnea and pediatric dysphagia. Using technologies such as electrophysiology, optogenetics, chemogenetics, confocal imaging, fiber photometry, and transgenic animal models, I helped expand our understanding of the precise roles that single nuclei as well as neuronal circuits play in modulating physiological changes in these disease states. For instance, we discovered that the dorsal raphe serotonin pathways mediated leptin preventing obstructive sleep apnea related to obesity; hypoglossal motoneurons phenotypic alteration and disrupted coordination in a pediatric dysphagia mouse model of DiGeorge syndrome. These findings would help us identify novel targets for future therapies.
Research
My research has been focused on the autonomic neural network regulation in (1) opioids and anesthetics complications; (2) ischemic heart disease, obstructive sleep apnea; and (3) pediatric dysphagia (difficult in feeding and swallowing).
Central molecular and cellular mechanisms by which opioids and anesthetics alter cardiorespiratory function
Opioids and anesthetics suppress cardiorespiratory function, even sudden death if overdose. We have studied the effects of volatile and intravenous anesthetics as well as three opioids (Kappa,,Delta, and Mu-opioids) on excitatory and inhibitory neurotransmission to the brainstem cardiac parasympathetic vagal neurons (CVNs), which dominates heart rate; the results show anesthetics differentially modulate the GABAergic and Glycinergic neurotransmission to the CVNs and trigeminocardiac reflex excitatory synaptic pathway in the brainstem and 5-Hydroxytryptamine 1A/7 and 4alpha receptors activation may prevent and reverse opioid-induced inhibition of brainstem cardio-respiratory function.
Autonomic neurocircuitry interaction; Neuroendocrine mechanisms of ischemic heart disease; and Role of oxytocin and leptin as potential mitigating factors
Parasympathetic and sympathetic system are the two divisions of autonomic nervous system. Autonomic function imbalance, especially increased sympathetic and decreased parasympathetic tone is common in ischemic heart disease and sleep apnea. Focused on the interaction between central catecholamine producing neuron, locus coeruleus noradrenergic neurons and cardiac vagal neurons in the nucleus ambiguus, as well as hypothalamic oxytocin and leptin pathway regulation, we have identified that neurotransmission alterations to parasympathetic cardiac vagal neurons in the brainstem and discovered chronic activation of hypothalamic oxytocin neurons improves cardiac function during left ventricular hypertrophy induced heart failure.
Hypoglossal motoneuron dysfunction and pediatric dysphagia
Using the DiGeorge/22q11.2 Deletion Syndrome mouse model and focusing on the hypoglossal motoneurons phenotype and neuronal networks, we investigated the developmental causes of feeding and swallowing in this disorder.
Teaching
Molecular Medicine 8281: Molecular Pharmacology and Neurobiology of Excitable Tissues
- Course director: 2014, 2015, 2016
- Wang X, Gorini C, Sharp D, Bateman R, Mendelowitz D. (2011) Anaesthetics differentially modulate the trigeminocardiac reflex excitatory synaptic pathway in the brainstem. J Physiol. 589 (Pt22):5431-42. PMID: 21930602
- Griffioen KJ, Wan R, Okun E, Wang X, Lovett-Barr MR, Li Y, Mughal MR, Mendelowitz D, Mattson MP. (2011) GLP-1 receptor stimulation depresses heart rate variability and inhibits neurotransmission to cardiac vagal neurons. Cardiovasc Res. 89(1):72-8.
- Wang X, (2009). Propofol and isoflurane enhancement of tonic GABA-A current in cardiac vagal neurons in the nucleus ambiguus. Anesthesia & Analgesia; 108(1): 142-148.
- Wang X, (2009). Nicotinic Receptors Partly Mediate Brainstem Autonomic Dysfunction Evoked by the Inhalation Anesthetic Isoflurane. Anesthesia & Analgesia Jan; 108(1): 134-141.
- Mc Dougall SJ, Peters JH, LaBrant L, Wang X, Koop DR, Andresen MC. (2008). Paired assessment of volatile anesthetic concentrations with synaptic actions recorded in vitro. PLoS ONE. 2008 Oct 8:3(10): e3372
- Wang X, Dergacheva O, Kamendi H, Gorini C, Mendelowitz D. (2007). 5-Hydroxytryptamine 1A/7 and 4alpha receptors differentially prevent opioid-induced inhibition of brain stem cardio-respiratory function. Hypertension. 50(2):368-76.
- Wang X, Huang ZG, Dergacheva O, Mendelowitz D. (2005). Ketamine inhibits inspiratory-evoked GABAergic and Glycinergic neurotransmission to cardiac vagal neurons in the nucleus ambiguus. Anesthesiology, 103(2):353-359.
- Wang X, Huang ZG, Gold A, Bouairi E, Evans C, Andresen MC, Mendelowitz D. (2004). Propofol modulates gamma-aminobutyric acid-mediated inhibitory neurotransmission to cardiac vagal neurons in the nucleus ambiguus. Anesthesiology, 100(5):1198-1205.
- Wang X, Evans C, Mendelowitz D. (2004). Voltage gated P/Q and N-type calcium channels mediate the nicotinic facilitation of GABAergic and glycinergic inputs to cardiac vagal neurons. Neuropharmacology, 46(3 Mar):372-378.
- Wang X; Dergacheva O; Griffioen K J S; Huang ZG; Evans C; Gold A; Bouairi E, Mendelowitz D. (2004). Action of kappa and Delta opioid agonists on premotor cardiac vagal neurons in the nucleus ambiguus. Neuroscience, 129(1):235-241.