Gang Wang - BMRI Neurovascular Biology and Stroke

Gang Wang, M.D./Ph.D. 
Associate Research Professor of Neuroscience

Overview

My research aims to understand cellular and molecular mechanisms underlying angiotensin II (Ang-II)-linked regulation of circulation, which include two parts: (1) the roles of reactive oxygen species (ROS) in Ang-II-elicited excitation of the brainstem and forebrain neurons; (2) the roles of chronic hypoxia-sensitive ion channels in the neuroplasticity of these central neurons. Our recent evidence suggests that ROS have participated in Ang-II signaling in these autonomic nuclei and play important roles in the regulation of the voltage-gated calcium influx and cardiovascular functions via the brainstem and forebrain nuclei such as the NTS, the SFO and the PVN. 

In the future, we will seek to uncover the roles of key prostanoid and/or TNF-α-linked signals, including PLA2, COX-1, COX-2, EP1R, TNF-α, nNOS and NADPH oxidase, in Ang-II-elicited production of ROS and nitric oxide, voltage-gated and/or NMDA receptor-mediated Ca2+ influx in vitro, and hypertension in vivo.

 

Achievements & Publications 

-In the PPG project, I provided the first evidence that in the brainstem NTS, NADPH oxidase assembly induced by Ang-II leads to substantial production of ROS which enhance the neuronal L-type Ca2+ channel current. These studies have established the concept that Ang-II-induced ROS production within NTS barosensory regions of the brainstem modulates the excitability of these neurons, which plays a role in the resetting of the baroreceptors in hypertension.

1. Wang G, Anrather J, Huang J, Speth RC, Pickel VM & Iadecola C (2004). NADPH oxidase contributes to angiotensin II signaling in the nucleus tractus solitarius. The Journal of Neuroscience 24: 5516-5524. 
2. Wang G, Lemos JR & Iadecola C (2004). Herbal alkaloid tetrandrine: from an ion channel blocker to a suppressor of tumor proliferation. Trends in Pharmacological Sciences 25: 120-123.
3. Kawano T, Anrather J, Zhou P, Park L, Wang G, Frys KA, Kunz A, Cho S, Orio M & Iadecola C (2006). Prostaglandin E2 EP1 receptors: downstream effectors of COX-2 neurotoxicity. Nature Medicine 12: 225-229. 
4. Wang G, Anrather J, Glass MJ, Tarsitano MJ, Zhou P, Frys KA, Pickel VM & Iadecola C (2006). Nox2, Ca2+ and PKC play a role in angiotensin II-induced free radical production in nucleus tractus solitarius. Hypertension 48: 482-489. 
5. Han XB, Wang F, Yao WX, Xing H, Weng DH, Song XH, Chen G, Xi L, Zhu T, Zhou JF, Xu G, Wang SX, Meng L, Iadecola C, Wang G & Ma D (2007). Heat shock proteins and p53 play a critical role in K+ channel-mediated tumor cell proliferation and apoptosis. Apoptosis 12: 1837-1846. 
6. Girouard H, Wang G, Zhou P, Anrather J & Iadecola C (2009). NMDA receptor activation increases free radical production through nitric oxide and NOX2. The Journal of Neuroscience 29: 2545-2552. 
7. Coleman CG, Wang G, Park L, Anrather J, Delagrammatikas GJ, Chan J, Zhou J, Iadecola C & Pickel VM (2010). Chronic intermittent hypoxia induces NMDA receptor-dependent plasticity and suppresses nitric oxide signaling in the mouse hypothalamic paraventricular nucleus. The Journal of Neuroscience 30: 12103-12112.
8. Park L, Wang G, Zhou P, Zhou J, Pitstick R, Prevti ML, Younkin L, Younkin S, van Nostrand WE, Cho S, Anrather J, Carlson G & Iadecola C (2011). The scavenger receptor CD36 is essential for the cerebrovascular oxidative stress and neurovascular dysfunction induced by amyloid-fl. The Proceedings of the National Academy of Sciences of the United States of America 108: 5063-5068. 
9. Young CN, Cao X, Guruju MR, Pierce JP, Morgan DA, Wang G, Iadecola C, Mark AL & Davisson RL (2012). Endoplasmic reticulum stress in the brain subfornical organ mediates angiotensin-dependent hypertension. The Journal of Clinical Investigation 122: 3960-3964.
10. Coleman C, Wang G, Faraco G, Lopes JM, Waters E, Milner TA, Iadecola C & Pickel VM (2013). Membrane trafficking of NADPH oxidase p47phox in paraventricular hypothalamic neurons parallels local free radical production in angiotensin II slow-pressor hypertension. The Journal of Neuroscience 33: 4308-4316