Bio

Professional Education


  • Exchange PhD student, Massachusetts General Hospital, Harvard Medical School, Cardiovascular Research (2012)
  • Doctor of Philosophy, University Of Hong Kong (2012)
  • Master of Science, Tsinghua University (2007)
  • Bachelor of Science, Tsinghua University (2005)

Stanford Advisors


Research & Scholarship

Current Research and Scholarly Interests


With various in vitro tools and in vivo mice models, I am focused on dissecting the roles of GRP124, GPR125 and Wnt signaling in CNS angiogenesis and vascular integrity after stroke from a translational perspective.

Publications

Journal Articles


  • Adiponectin Prevents Diabetic Premature Senescence of Endothelial Progenitor Cells and Promotes Endothelial Repair by Suppressing the p38 MAP Kinase/p16(INK4A) Signaling Pathway DIABETES Chang, J., Li, Y., Huang, Y., Lam, K. S., Hoo, R. L., Wong, W. T., Cheng, K. K., Wang, Y., Vanhoutte, P. M., Xu, A. 2010; 59 (11): 2949-2959

    Abstract

    A reduced number of circulating endothelial progenitor cells (EPCs) are casually associated with the cardiovascular complication of diabetes. Adiponectin exerts multiple protective effects against cardiovascular disease, independent of its insulin-sensitizing activity. The objective of this study was to investigate whether adiponectin plays a role in modulating the bioavailability of circulating EPCs and endothelial repair.Adiponectin knockout mice were crossed with db(+/-) mice to produce db/db diabetic mice without adiponectin. Circulating number of EPCs were analyzed by flow cytometry. Reendothelialization was evaluated by staining with Evans blue after wire-induced carotid injury.In adiponectin knockout mice, the number of circulating EPCs decreased in an age-dependent manner compared with the wild-type controls, and this difference was reversed by the chronic infusion of recombinant adiponectin. In db/db diabetic mice, the lack of adiponectin aggravated the hyperglycemia-induced decrease in circulating EPCs and also diminished the stimulatory effects of the PPAR? agonist rosiglitazone on EPC production and reendothelialization. In EPCs isolated from both human peripheral blood and mouse bone marrow, treatment with adiponectin prevented high glucose-induced premature senescence. At the molecular level, adiponectin decreased high glucose-induced accumulation of intracellular reactive oxygen species and consequently suppressed activation of p38 MAP kinase (MAPK) and expression of the senescence marker p16(INK4A).Adiponectin prevents EPC senescence by inhibiting the ROS/p38 MAPK/p16(INK4A) signaling cascade. The protective effects of adiponectin against diabetes vascular complications are attributed in part to its ability to counteract hyperglycemia-mediated decrease in the number of circulating EPCs.

    View details for DOI 10.2337/db10-0582

    View details for Web of Science ID 000284133400034

    View details for PubMedID 20802255

  • Soluble Guanylate Cyclase alpha 1 beta 1 Limits Stroke Size and Attenuates Neurological Injury STROKE Atochin, D. N., Yuzawa, I., Li, Q., Rauwerdink, K. M., Malhotra, R., Chang, J., Brouckaert, P., Ayata, C., Moskowitz, M. A., Bloch, K. D., Huang, P. L., Buys, E. S. 2010; 41 (8): 1815-1819

    Abstract

    Nitric oxide mediates endothelium-dependent vasodilation, modulates cerebral blood flow, and determines stroke outcome. Nitric oxide signals in part by stimulating soluble guanylate cyclase (sGC) to synthesize cGMP. To study the role of sGC in stroke injury, we compared the outcome of cerebral ischemia and reperfusion in mice deficient in the alpha(1) subunit of sGC (sGCalpha(1)(-/-)) with that in wild-type mice.Blood pressure, cerebrovascular anatomy, and vasoreactivity of pressurized carotid arteries were compared in both mouse genotypes. Cerebral blood flow was measured before and during middle cerebral artery occlusion and reperfusion. We then assessed neurological deficit and infarct volume after 1 hour of occlusion and 23 hours of reperfusion and after 24 hours of occlusion.Blood pressure and cerebrovascular anatomy were similar between genotypes. We found that vasodilation of carotid arteries in response to acetylcholine or sodium nitroprusside was diminished in sGCalpha(1)(-/-) compared with wild-type mice. Cerebral blood flow deficits did not differ between the genotypes during occlusion, but during reperfusion, cerebral blood flow was 45% less in sGCalpha(1)(-/-) mice. Infarct volumes and neurological deficits were similar after 24 hours of occlusion in both genotypes. After 1 hour of ischemia and 23 hours of reperfusion, infarct volumes were 2-fold larger and neurological deficits were worse in sGCalpha(1)(-/-) than in the wild-type mice.sGCalpha(1) deficiency impairs vascular reactivity to nitric oxide and is associated with incomplete reperfusion, larger infarct size, and worse neurological damage, suggesting that cGMP generated by sGCalpha(1)beta(1) is protective in ischemic stroke.

    View details for DOI 10.1161/STROKEAHA.109.577635

    View details for Web of Science ID 000280330700037

    View details for PubMedID 20595671

  • ApoE 4 reduces the expression of A beta degrading enzyme IDE by activating the NMDA receptor in hippocampal neurons NEUROSCIENCE LETTERS Du, J., Chang, J., Guo, S., Zhang, Q., Wang, Z. 2009; 464 (2): 140-145

    Abstract

    Apolipoprotein E (ApoE) 4 is a potent risk factor for Alzheimer's disease (AD). However, the mechanism underlying ApoE4 function in the pathology of AD is not well understood. We report here that, in comparison with ApoE2 and ApoE3, ApoE4 significantly reduces levels of insulin-degrading enzyme (IDE), which is responsible for the cellular clearance of Abeta in neurons. This differential regulation of IDE by various ApoE isoforms was blocked by coincubation with N-methyl-d-aspartic acid (NMDA) receptor inhibitors and receptor-associated protein (RAP), which blocked the interaction between ApoE and members of the low-density lipoprotein (LDL) receptor family. Moreover, inhibition of the NMDA receptor increased IDE levels in neurons, while activation of the NMDA receptor-reduced IDE expression. Further studies demonstrate that, as a pathway downstream of the NMDA receptor, cAMP-dependent protein kinase (PKA) contributes to the NMDA receptor-reduced IDE expression. These results suggest that ApoE4 down-regulates IDE expression in neurons by binding to its receptor and stimulating the NMDA receptor pathway, which may account for its role in AD pathogenesis.

    View details for DOI 10.1016/j.neulet.2009.07.032

    View details for Web of Science ID 000270419400014

    View details for PubMedID 19616072

  • Endoplasmic reticulum mediated necrosis-like apoptosis of Hela cells induced by Ca2+ oscillation JOURNAL OF BIOCHEMISTRY AND MOLECULAR BIOLOGY Hu, Q. L., Chang, J. L., Tao, L. T., Yan, G. L., Xie, M. C., Wang, Z. 2005; 38 (6): 709-716

    Abstract

    Apoptosis and necrosis are distinguished by modality primarily. Here we show an apoptosis occurred instantly, induced by 300 muM W-7 ((N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride), inhibitor of calmodulin), which demonstrated necrotic modality. As early as 30 min after W-7 addition, apoptotic (sub-diploid) peak could be detected by fluorescence-activated cell sorter (FACS), "DNA ladders" began to emerge also at this time point, activity of caspase-3 elevated obviously within this period. Absence of mitochondrial membrane potential (MMP) reduction and cytochrome c, AIF (apoptosis inducing factor) release, verified that this rapid apoptosis did not proceed through mitochondria pathway. Activation of caspase-12 and changes of other endoplasmic reticulum (ER) located proteins ascertained that ER pathway mediated this necrosis-like apoptosis. Our findings suggest that it is not credible to judge apoptosis by modality. Elucidation of ER pathway is helpful to comprehend the pathology of diseases associated with ER stress, and may offer a new approach to the therapy of cancer and neurodegenerative diseases.

    View details for Web of Science ID 000233627800012

    View details for PubMedID 16336787

Stanford Medicine Resources: