Zhao Lab Research
Recovery of endothelial integrity after vascular injury is vital for endothelial barrier function and vascular homeostasis. Endothelial dysfunction
plays a critical role in the initiation and progression of vascular diseases such as atherosclerosis and acute lung injury. A part of the research in the lab is to
elucidate the molecular mechanisms of endothelial repair, and endothelial progenitor cells-mediated endothelial regeneration and neovascularization using the unique
mouse model with endothelial cell-restricted deletion of FoxM1 (J. Clin. Invest., 2006, 116: 2333).
Pulmonary hypertension is a progressive disease with high mortality. Caveolin-1, the scaffolding protein of caveolae is implicated in pulmonary
hypertension and fibrosis (Proc. Natl. Acad. Sci., USA, 2002, 99: 11375). We are currently investigating the underlying molecular mechanism using genetic knockout
mouse models and pharmacological approaches. The lab is also working on mechanisms of other lung diseases such as acute lung injury.
- Mirza, M.K., Sun, Y., Zhao, Y.D., Potula, H.H.S.K., Frey, R.S., Vogel, S.M., Malik, A.B., and Zhao, Y.Y. FoxM1 regulates re-annealing of endothelial adherens junctions through transcriptional control of b-catenin. The Journal of Experimental Medicine. 2010, 207:1675-1685.
- Mirza, M.K., Yuan, J., Gao, X.P., Garrean, S., Brovkovych, V., Malik, A.B., Tiruppathi, C., and Zhao, Y.Y. Caveolin-1 deficiency dampens Toll-like receptor 4 signaling through eNOS activation. Am J Pathol. 2010, 176: 2344-2351.
- Zhao, Y.D., Ohkawara, H., Vogel, S.M., Malik, A.B., and Zhao, Y.Y. Bone marrow-derived progenitor cells prevent thrombin-induced increase in lung vascular permeability. Am J Physiol Lung Cell Mol Physiol. 2010, 298:L36-44.
- Zhao, Y.Y. and Malik A.B. A novel insight into the mechanism of pulmonary hypertension: Involving Caveolin-1 deficiency and eNOS activation. Trends in Cardiovascular Medicine. 2009, 19:238-242.
- Zhao, Y.D., Rehman, J., Ohkawara, H., Wary, K.K., Vogel, S.M., Minshall, R.D., Zhao, Y.Y., and Malik, A.B. Bone marrow progenitor cells induce endothelial adherens junction integrity by sphingosine-1-phosphate-mediated Rac1 and Cdc42 signaling. Cir Res. 2009, 105:696-704.
- Zhao, Y.Y.*, Zhao, Y.D., Mirza, M.K., Huang, J.H., Potula, H.H.S.K., Vogel, S.M., Brovkovych, V., Yuan, J.X.J., Wharton, J., and Malik, A.B. Persistent eNOS activation secondary to caveolin-1 deficiency induces pulmonary hypertension in mice and humans through protein kinase G nitration. J Clin Invest. 2009, 119:2009-2018.
- Xu, J., Gao, X.P., Ramchandran, R., Zhao, Y.Y., Vogel, S.M., and Malik, A.B. 2008. Non-muscle MLCK mediates neutrophil transmigration in sepsis-induced lung inflammation by activation of b2 integrins. Nat Immunol. 2008, 9:880-886.
- Zhao YY*, Gao XP, Zhao YD, Mirza MK, Frey RS, Wang IC, Kalinichenko VV, Costa RH, and Malik AB. Endothelial cell-restricted disruption of FoxM1 impairs endothelial repair following LPS-induced vascular injury. J Clin Invest. 2006, 116:2333-2343.
- Zhao YY, Liu Y, Stan RV, Fan L, Gu Y, Dalton N, Chu PH, Peterson K, Ross J, Jr., and Chien, KR. Defects in caveolin-1 cause dilated cardiomyopathy and pulmonary hypertension in knockout mice. Proc Natl Acad Sci, USA. 2002, 99:11375-11380.
- Crone S*, Zhao YY* Fan L, Gu YS, Minamisawa S, Peterson K, Chen J, Kahn R,
Condorelli G, Ross J, Jr., Chien KR, and Lee KF. ErbB2 myocyte survival pathways are essential in the prevention of dilated cardiomyopathy. Nat Med. 2002, 8:459-465.
(* Contributed equally).
- Zhao YY, Feron O, Dessy C, Han XQ, Marchionni MA, Kelly RA. Neuregulin Signaling in the heart: dynamic targeting of ErbB4 to caveolar microdomains in cardiac myocytes. Circ Res. 1999, 84:1380-1387.
- Zhao YY, Sawyer DR, Baliga RR, Opel DJ, Han XQ, Marchionni MA, Kelly RA. Neuregulins promote survival and growth of cardiac myocytes: persistence of erbB2 and erbB4 expression in neonatal and adult myocardium. J Biol Chem. 1998, 273:10261-10269.