I am a postdoctoral research fellow in Dr. Gary Steinberg's lab in the Department of Neurosurgery. My main interest is to understand the underlying cellular and molecular mechanisms after stroke and to find the therapeutic targets for brain repair and stroke recovery. My PhD. thesis work demonstrated the acute and sustained neuroprotection by the pharmacological hypothermia in ischemic stroke animal model, providing a novel hypothermia treatment for stroke application. Before that, I detected the role of innate immune signaling pathways from toll-like-receptor family in myocardial infarction. My current work focuses on using optogenetic strategies to stimulate the targeted neurons for brain repair after stroke and detecting the neural circuit and molecular mechanisms underlying the stroke recovery.
Honors & Awards
Postdoctoral Fellowship, American Heart Association (AHA ) (2017-2019)
Best Poster award in Third Annual cardiovascular Research Institute Symposium, Baylor College of Medicine, Houston, TX (2015)
Dean’s Awards for Excellence, Baylor College of Medicine, Houston, TX (2015)
First Place Award for Best Posters at the 27th BCM Annual Graduate Student Symposium,, Baylor College of Medicine, Houston, TX (2015)
Third place poster award, Medical World Americas Conference, Houston, TX (2015)
Pre-doctoral Fellowship, American Heart Association (AHA ) (2013-2015)
Outstanding graduation thesis, Nanjing Medical University, Nanjing, Jiangsu, China (2010)
Boards, Advisory Committees, Professional Organizations
Member, American Heart Association (2011 - Present)
Member, American Physiological Society (2012 - Present)
Doctor of Philosophy, Baylor College Of Medicine (2016)
Master of Science, Nanjing Medical University (2009)
Doctor of Medicine, Yangzhou University Medical College (2004)
Gary Steinberg, Postdoctoral Faculty Sponsor
Current Research and Scholarly Interests
My current research focuses on:
1) using optogenetic strategies to stimulate targeted neurons for brain repair after stroke.
2) detecting the neural circuit and molecular mechanisms underlying stroke recovery.
- RNA-Sequencing Analysis Revealed a Distinct Motor Cortex Transcriptome in Spontaneously Recovered Mice After Stroke STROKE 2018; 49 (9): 2191–99
TRPV1-mediated Pharmacological Hypothermia Promotes Improved Functional Recovery Following Ischemic Stroke.
2017; 7 (1): 17685
Hypothermia shows promise for stroke neuroprotection, but current cooling strategies cause undesirable side effects that limit their clinical applications. Increasing efforts have focused on pharmacological hypothermia as a treatment option for stroke. Previously, we showed that activation of a thermoregulatory ion channel, transient receptor potential vanilloid 1 (TRPV1), by dihydrocapsaicin (DHC) produces reliable hypothermia. In this study, we investigate the effects of TRPV1-mediated hypothermia by DHC on long-term ischemic stroke injury and functional outcome. Hypothermia initiated at 3.5 hours after stroke significantly reduced primary cortical injury. Interestingly, hypothermia by DHC also significantly reduced secondary thalamic injury, as DHC-treated stroke mice exhibited 53% smaller thalamic lesion size. DHC-treated stroke mice further demonstrated decreased neuronal loss and astrogliosis in the thalamus and less thalamic fiber loss by diffusion tensor imaging (DTI). Importantly, a single 8 hour treatment of hypothermia by DHC after stroke provided long-term improvement in functional outcome, as DHC-treated mice exhibited improved behavioral recovery at one month post-stroke. These findings indicate that TRPV1-mediated hypothermia is effective in reducing both primary cortical injury and remote secondary thalamic injury, and a single treatment can produce persistent effects on functional recovery. These data highlight the therapeutic potential for TRPV1 agonism for stroke treatment.
View details for DOI 10.1038/s41598-017-17548-y
View details for PubMedID 29247238
View details for PubMedCentralID PMC5732157
Transient Receptor Potential Melastatin 8 Channel Inhibition Potentiates the Hypothermic Response to Transient Receptor Potential Vanilloid 1 Activation in the Conscious Mouse
CRITICAL CARE MEDICINE
2014; 42 (5): E355-E363
Mild decrease in core temperature (therapeutic hypothermia) provides lasting neuroprotection following cardiac arrest or cerebral ischemia. However, current methods for producing therapeutic hypothermia trigger a cold-defense response that must be countered by sedatives, muscle paralytics, and mechanical ventilation. We aimed to determine methods for producing hypothermia in the conscious mouse by targeting two transient receptor potential channels involved in thermoregulation, two transient receptor potential (TRP) channels involved in thermoregulation, TRP vanilloid 1 (TRPV1) and TRP melastatin 8 (TRPM8).Controlled prospective animal study.Research laboratory at academic medical center.Conscious unrestrained young and aged male mice.Mice were treated with the TRPV1 agonist dihydrocapsaicin, a TRPM8 inhibitor ("compound 5"), or their combination and the effects on core temperature (Tcore) were measured by implanted thermocouples and wireless transponders.TRPV1 agonist dihydrocapsaicin produced a dose-dependent (2-4 mg/kg s.c.) drop in Tcore. A loading dose followed by continuous infusion of dihydrocapsaicin produced a rapid and prolonged (> 6 hr) drop of Tcore within the therapeutic range (32-34°C). The hypothermic effect of dihydrocapsaicin was augmented in aged mice and was not desensitized with repeated administration. TRPM8 inhibitor "compound 5" (20 mg/kg s.c.) augmented the drop in core temperature during cold exposure (8°C). When "compound 5" (30 mg/kg) was combined with dihydrocapsaicin (1.25-2.5 mg/kg), the drop in Tcore was amplified and prolonged.Activating warm receptors (TRPV1) produced rapid and lasting hypothermia in young and old mice. Furthermore, hypothermia induced by TRPV1 agonists was potentiated and prolonged by simultaneous inhibition of TRPM8.
View details for DOI 10.1097/CCM.0000000000000229
View details for Web of Science ID 000335383900004
View details for PubMedID 24595220
Pharmacologically induced hypothermia via TRPV1 channel agonism provides neuroprotection following ischemic stroke when initiated 90 min after reperfusion
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
2014; 306 (2): R149-R156
Traditional methods of therapeutic hypothermia show promise for neuroprotection against cerebral ischemia-reperfusion (I/R), however, with limitations. We examined effectiveness and specificity of pharmacological hypothermia (PH) by transient receptor potential vanilloid 1 (TRPV1) channel agonism in the treatment of focal cerebral I/R. Core temperature (T(core)) was measured after subcutaneous infusion of TRPV1 agonist dihydrocapsaicin (DHC) in conscious C57BL/6 WT and TRPV1 knockout (KO) mice. Acute measurements of heart rate (HR), mean arterial pressure (MAP), and cerebral perfusion were measured before and after DHC treatment. Focal cerebral I/R (1 h ischemia + 24 h reperfusion) was induced by distal middle cerebral artery occlusion. Hypothermia (>8 h) was initiated 90 min after start of reperfusion by DHC infusion (osmotic pump). Neurofunction (behavioral testing) and infarct volume (TTC staining) were measured at 24 h. DHC (1.25 mg/kg) produced a stable drop in T(core) (33°C) in naive and I/R mouse models but not in TRPV1 KO mice. DHC (1.25 mg/kg) had no measurable effect on HR and cerebral perfusion but produced a slight transient drop in MAP (<6 mmHg). In stroke mice, DHC infusion produced hypothermia, decreased infarct volume by 87%, and improved neurofunctional score. The hypothermic and neuroprotective effects of DHC were absent in TRPV1 KO mice or mice maintained normothermic with heat support. PH via TRPV1 agonist appears to be a well-tolerated and effective method for promoting mild hypothermia in the conscious mouse. Furthermore, TRPV1 agonism produces effective hypothermia in I/R mice and significantly improves outcome when initiated 90 min after start of reperfusion.
View details for DOI 10.1152/ajpregu.00329.2013
View details for Web of Science ID 000329854000007
View details for PubMedID 24305062
View details for PubMedCentralID PMC3921315
CpG-ODN, the TLR9 agonist, attenuates myocardial ischemia/reperfusion injury: Involving activation of PI3K/Akt signaling
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
2013; 1832 (1): 96-104
Toll-like receptors (TLRs) have been implicated in myocardial ischemia/reperfusion (I/R) injury. The TLR9 ligand, CpG-ODN has been reported to improve cell survival. We examined effect of CpG-ODN on myocardial I/R injury.Male C57BL/6 mice were treated with either CpG-ODN, control-ODN, or inhibitory CpG-ODN (iCpG-ODN) 1h prior to myocardial ischemia (60min) followed by reperfusion. Untreated mice served as I/R control (n=10/each group). Infarct size was determined by TTC straining. Cardiac function was examined by echocardiography before and after myocardial I/R up to 14days.CpG-ODN administration significantly decreased infarct size by 31.4% and improved cardiac function after myocardial I/R up to 14days. Neither control-ODN nor iCpG-ODN altered I/R-induced myocardial infarction and cardiac dysfunction. CpG-ODN attenuated I/R-induced myocardial apoptosis and prevented I/R-induced decrease in Bcl2 and increase in Bax levels in the myocardium. CpG-ODN increased Akt and GSK-3β phosphorylation in the myocardium. In vitro data suggested that CpG-ODN treatment induced TLR9 tyrosine phosphorylation and promoted an association between TLR9 and the p85 subunit of PI3K. Importantly, PI3K/Akt inhibition and Akt kinase deficiency abolished CpG-ODN-induced cardioprotection.CpG-ODN, the TLR9 ligand, induces protection against myocardial I/R injury. The mechanisms involve activation of the PI3K/Akt signaling pathway.
View details for DOI 10.1016/j.bbadis.2012.08.008
View details for Web of Science ID 000313932000011
View details for PubMedID 22917564
View details for PubMedCentralID PMC3518630
The TIR/BB-loop mimetic AS-1 protects the myocardium from ischaemia/reperfusion injury
2009; 84 (3): 442-451
Innate immune and inflammatory responses are involved in myocardial ischaemia/reperfusion (I/R) injury. The interleukin-1 receptor (IL-1R)-mediated, MyD88-dependent nuclear factor kappa B (NF-kappaB) activation pathway plays an important role in the induction of innate immunity and inflammation. However, the role of the IL-1R-MyD88 pathway in myocardial I/R injury has not been thoroughly investigated. We hypothesized that inhibition of the interaction of IL-1R with MyD88 will attenuate myocardial ischaemic injury through reducing inflammatory responses.Male C57BL/6 mice were subjected to myocardial ischaemia (45 min) followed by reperfusion (4 h). In the treatment group, after mice were subjected to ischaemia (45 min), the TIR/BB-loop mimetic (AS-1), which inhibits the interaction of IL-1R with MyD88, was administered immediately before reperfusion. Hearts were harvested and cellular proteins were isolated for immunoprecipitation and immunoblotting. AS-1 administration significantly decreased infarct size by 32.92% compared with the untreated I/R group. Ejection fraction and fractional shortening in AS-1-treated mice were also significantly increased by 18.0 and 25.6%, respectively, compared with the untreated I/R group. AS-1 administration significantly decreased the I/R-increased interaction between IL-1R and MyD88, attenuated the I/R-increased NF-kappaB binding activity, and reduced levels of inflammatory cytokines and adhesion molecules in the myocardium compared with the untreated I/R group. In addition, AS-1 administration significantly decreased myocardial myeloperoxidase activity by 23.6% and neutrophil infiltration in the myocardium compared with the untreated I/R group.The results demonstrated an important role for the IL-1R-mediated MyD88-dependent signalling pathway in myocardial I/R injury. The data suggest that modulation of the IL-1R/MyD88 interaction could be a strategy for reducing myocardial ischaemic injury.
View details for DOI 10.1093/cvr/cvp234
View details for Web of Science ID 000272084800016
View details for PubMedID 19586942
Carbamylated erythropoietin protects the myocardium from acute ischemia/reperfusion injury through a PI3K/Akt-dependent mechanism
2009; 146 (3): 506-514
Erythropoietin (EPO) and carbamylated erythropoietin (CEPO) can protect tissue from injury; however, CEPO has its protective effect in the absence of erythropoietic stimulation. The mechanism whereby CEPO protects heart from acute ischemia/reperfusion (I/R) injury remains unknown.BALB/c mice were subjected to myocardial ischemia for 45 min followed by reperfusion for 4 h, and they received a single dose of CEPO intraperitoneal at the onset of reperfusion. Myocardial infarct size and cardiac function were assessed. The association of erythropoietin receptor with beta common receptor (betacR) was examined. The level of Akt phosphorylation in the myocardium was assayed as well as a series of downstream target genes of PI3K/Akt,including p-GATA-4, GATA-4, MHC, and troponin I.CEPO administration immediately before reperfusion decreased infarction by 40% and increased ejection fraction (27%) and fractional shortening (22%), compared with untreated ischemic hearts (P < .05 each). CEPO promoted association of the EPO receptor and betacR. Furthermore, CEPO administration increased the levels of phospho-Akt in the myocardium by 59% (P < .05). A PI3K inhibitor, wortmannin, blocked the beneficial effect of CEPO on infarct size and cardiac function and attenuated the CEPO-induced Akt phosphorylation. CEPO also increased the expression of p-GATA-4, GATA-4, myosin heavy chain, and troponin I.A single dose of CEPO at the onset of reperfusion attenuated acute myocardial I/R injury in the mouse. CEPO-induced cardioprotection appears to be mediated through a PI3K/Akt-dependent mechanism.
View details for DOI 10.1016/j.surg.2009.03.022
View details for Web of Science ID 000269680600017
View details for PubMedID 19715808
- Dephosphorylation of cardiomyocyte Cx43 is associated with myocardial ischemia and reperfusion injury Journal of Nanjing Medical University 2009; 23 (3): 163-167
- Nonhematopoietic erythropoietin derivative protects cardiomyocytes from hypoxia/reoxygenation-induced apoptosis Journal of Nanjing Medical University 2008; 22 (2): 71-74