Imperial College London

ProfessorLanZhao

Faculty of MedicineDepartment of Medicine

Professor of Experimental Medicine
 
 
 
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Contact

 

+44 (0)20 7594 6823l.zhao

 
 
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Location

 

531ICTEM buildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

68 results found

Kiely D, Levin D, Hassoun P, Ivy DD, Jone P-N, Bwika J, Kawut SM, Lordan J, Lungu A, Mazurek J, Moledina S, Olschewski H, Peacock A, Puri GD, Rahaghi F, Schafer M, Schiebler M, Screaton N, Tawhai M, Van Beek EJ, Vonk-Noordegraaf A, Vanderpool RR, Wort J, Zhao L, Wild J, Vogel-Claussen J, Swift Aet al., 2019, EXPRESS: Statement on imaging and pulmonary hypertension from the Pulmonary Vascular Research Institute (PVRI)., Pulm Circ, ISSN: 2045-8932

JOURNAL ARTICLE

Abdul-Salam VB, Russomanno G, Chien-Nien C, Mahomed AS, Yates LA, Wilkins MR, Zhao L, Gierula M, Dubois O, Schaeper U, Endruschat J, Wojciak-Stothard Bet al., 2019, CLIC4/Arf6 Pathway A New Lead in BMPRII Inhibition in Pulmonary Hypertension, CIRCULATION RESEARCH, Vol: 124, Pages: 52-65, ISSN: 0009-7330

JOURNAL ARTICLE

Ashek A, Spruijt OA, Harms HJ, Lammertsma AA, Cupitt J, Dubois O, Wharton J, Dabral S, Pullamsetti SS, Huisman MC, Frings V, Boellaard R, de Man FS, Botros L, Jansen S, Noordegraaf AV, Wilkins MR, Bogaard HJ, Zhao Let al., 2018, 3 '-deoxy-3'-[18F]fluorothymidine positron emission tomography depicts heterogeneous proliferation pathology in idiopathic pulmonary arterial hypertension patient lung: a potential biomarker for pulmonary arterial hypertension, Circulation: Cardiovascular Imaging, Vol: 11, ISSN: 1941-9651

Background:Pulmonary vascular cell hyperproliferation is characteristic of pulmonary vascular remodeling in pulmonary arterial hypertension. A noninvasive imaging biomarker is needed to track the pathology and assess the response to novel treatments targeted at resolving the structural changes. Here, we evaluated the application of radioligand 3′-deoxy-3′-[18F]-fluorothymidine (18FLT) using positron emission tomography.Methods and Results:We performed dynamic 18FLT positron emission tomography in 8 patients with idiopathic pulmonary arterial hypertension (IPAH) and applied in-depth kinetic analysis with a reversible 2-compartment 4k model. Our results show significantly increased lung 18FLT phosphorylation (k3) in patients with IPAH compared with nonpulmonary arterial hypertension controls (0.086±0.034 versus 0.054±0.009 min−1; P<0.05). There was heterogeneity in the lung 18FLT signal both between patients with IPAH and within the lungs of each patient, compatible with histopathologic reports of lungs from patients with IPAH. Consistent with 18FLT positron emission tomographic data, TK1 (thymidine kinase 1) expression was evident in the remodeled vessels in IPAH patient lung. In addition, hyperproliferative pulmonary vascular fibroblasts isolated from patients with IPAH exhibited upregulated expression of TK1 and the thymidine transporter, ENT1 (equilibrative nucleoside transporter 1). In the monocrotaline and SuHx (Sugen hypoxia) rat pulmonary arterial hypertension models, increased lung 18FLT uptake was strongly associated with peripheral pulmonary vascular muscularization and the proliferation marker, Ki-67 score, together with prominent TK1 expression in remodeled vessels. Importantly, lung 18FLT uptake was attenuated by 2 antiproliferative treatments: dichloroacetate and the tyrosine kinase inhibitor, imatinib.Conclusions:Dynamic 18FLT positron emission tomography imaging can be used to report hyperproliferation in pulmonary h

JOURNAL ARTICLE

Michelakis ED, Gurtu V, Webster L, Barnes G, Watson G, Howard L, Cupitt J, Paterson I, Thompson RB, Chow K, O'Regan DP, Zhao L, Wharton J, Kiely DG, Kinnaird A, Boukouris AE, White C, Nagendran J, Freed DH, Wort SJ, Gibbs JSR, Wilkins MRet al., 2017, Inhibition of pyruvate dehydrogenase kinase improves pulmonary arterial hypertension in genetically susceptible patients, SCIENCE TRANSLATIONAL MEDICINE, Vol: 9, ISSN: 1946-6234

JOURNAL ARTICLE

Duluc L, Ahmetaj-Shala B, Mitchell J, Abdul-Salam VB, Mahomed AS, Aldabbous L, Oliver E, Iannone L, Dubois OD, Storck EM, Tate EW, Zhao L, Wilkins MR, Wojciak-Stothard Bet al., 2017, Tipifarnib prevents development of hypoxia-induced pulmonary hypertension, CARDIOVASCULAR RESEARCH, Vol: 113, Pages: 276-287, ISSN: 0008-6363

JOURNAL ARTICLE

Ashek A, Dubois O, Wilkins M, Zhao Let al., 2016, Kinetic Analysis Of 3 '-Deoxy-3 '-[18f]-Fluorothymidine (flt) Positron Emission Tomography (pet) In Monocrotaline-Induced Pulmonary Hypertension Rat, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X

CONFERENCE PAPER

Zhao L, Oliver E, Maratou K, Atanur SS, Dubois OD, Cotroneo E, Chen C-N, Wang L, Arce C, Chabosseau PL, Ponsa-Cobas J, Frid MG, Moyon B, Webster Z, Aldashev A, Ferrer J, Rutter GA, Stenmark KR, Aitman TJ, Wilkins MRet al., 2015, The zinc transporter ZIP12 regulates the pulmonary vascular response to chronic hypoxia, NATURE, Vol: 524, Pages: 356-U229, ISSN: 0028-0836

JOURNAL ARTICLE

Cotroneo E, Ashek A, Wang L, Wharton J, Dubois O, Bozorgi S, Busbridge M, Alavian KN, Wilkins MR, Zhao Let al., 2015, Iron Homeostasis and Pulmonary Hypertension Iron Deficiency Leads to Pulmonary Vascular Remodeling in the Rat, CIRCULATION RESEARCH, Vol: 116, Pages: 1680-1690, ISSN: 0009-7330

JOURNAL ARTICLE

Wilkins MR, Ghofrani H-A, Weissmann N, Aldashev A, Zhao Let al., 2015, Pathophysiology and Treatment of High-Altitude Pulmonary Vascular Disease, CIRCULATION, Vol: 131, Pages: 582-590, ISSN: 0009-7322

JOURNAL ARTICLE

Ashek A, Tang SP, Dubois O, Coello C, Ashworth S, Passchier J, Wilkins MR, Zhao Let al., 2014, Quantification of respiratory inflammation with [11C]PBR28 in a rodent model of pulmonary arterial hypertension, Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), Publisher: SPRINGER, Pages: S389-S389, ISSN: 1619-7070

CONFERENCE PAPER

Francis BN, Hale A, Channon KM, Wilkins MR, Zhao Let al., 2014, Effects of tetrahydrobiopterin oral treatment in hypoxia-induced pulmonary hypertension in rat, PULMONARY CIRCULATION, Vol: 4, Pages: 462-470, ISSN: 2045-8932

JOURNAL ARTICLE

Iannone L, Zhao L, Dubois O, Duluc L, Rhodes CJ, Wharton J, Wilkins MR, Leiper J, Wojciak-Stothard Bet al., 2014, miR-21/DDAH1 pathway regulates pulmonary vascular responses to hypoxia, BIOCHEMICAL JOURNAL, Vol: 462, Pages: 103-112, ISSN: 0264-6021

JOURNAL ARTICLE

Wojciak-Stothard B, Abdul-Salam VB, Lao KH, Tsang H, Irwin DC, Lisk C, Loomis Z, Stenmark KR, Edwards JC, Yuspa SH, Howard LS, Edwards RJ, Rhodes CJ, Gibbs JSR, Wharton J, Zhao L, Wilkins MRet al., 2014, Aberrant Chloride Intracellular Channel 4 Expression Contributes to Endothelial Dysfunction in Pulmonary Arterial Hypertension, CIRCULATION, Vol: 129, Pages: 1770-1780, ISSN: 0009-7322

JOURNAL ARTICLE

George PM, Oliver E, Dorfmuller P, Dubois OD, Reed DM, Kirkby NS, Mohamed NA, Perros F, Antigny F, Fadel E, Schreiber BE, Holmes AM, Southwood M, Hagan G, Wort SJ, Bartlett N, Morrell NW, Coghlan JG, Humbert M, Zhao L, Mitchell JAet al., 2014, Evidence for the Involvement of Type I Interferon in Pulmonary Arterial Hypertension, CIRCULATION RESEARCH, Vol: 114, Pages: 677-688, ISSN: 0009-7330

JOURNAL ARTICLE

Iannone L, Leiper J, Zhao L, Wilkins MR, Wojciak-Stothard Bet al., 2014, Ddah1 Regulates Pulmonary Vascular Responses To Hypoxia Via Mir-21, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 189, ISSN: 1073-449X

JOURNAL ARTICLE

Cotroneo E, Ashek A, Wharton J, Dubois O, Bozorgi S, Busbridge M, Wilkins M, Zhao Let al., 2014, Pulmonary Vascular Remodelling In The Chronic Iron-Deficient Rat, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 189, ISSN: 1073-449X

JOURNAL ARTICLE

Watson G, Oliver E, Zhao L, Wilkins MRet al., 2013, Pulmonary hypertension: Old targets revisited (Statins, PPARs, Beta-Blockers), Handbook of Experimental Pharmacology, Vol: 218, Pages: 531-548, ISSN: 0171-2004

Pulmonary arterial hypertension is a therapeutic challenge. Despite progress in recent years with three drug classes-prostanoids, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors-long-term patient survival remains poor. Importantly, the introduction and commercial success of these new treatments has been accompanied by growing interest in the pathology of pulmonary hypertension. This, in turn, has stimulated a re-evaluation of the molecular factors driving the structural remodelling of pulmonary arterioles and the opportunities to preserve right ventricular function in pulmonary hypertension. Academics with restricted access to new chemicals have turned to existing drugs to investigate new ideas. It is in this context that the role of statins, peroxisome proliferator-activated receptors (PPARs) and beta-blockers are of interest as potential treatments for pulmonary hypertension. © Springer-Verlag Berlin Heidelberg 2013.

JOURNAL ARTICLE

Zhao L, Ashek A, Wang L, Fang W, Dabral S, Dubois O, Cupitt J, Pullamsetti SS, Cotroneo E, Jones H, Tomasi G, Quang-De N, Aboagye EO, El-Bahrawy MA, Barnes G, Howard LS, Gibbs JSR, Gsell W, He J-G, Wilkins MRet al., 2013, Heterogeneity in Lung (18)FDG Uptake in Pulmonary Arterial Hypertension Potential of Dynamic (18)FDG Positron Emission Tomography With Kinetic Analysis as a Bridging Biomarker for Pulmonary Vascular Remodeling Targeted Treatments, CIRCULATION, Vol: 128, Pages: 1214-1224, ISSN: 0009-7322

JOURNAL ARTICLE

Wang L, Guo L-J, Liu J, Wang W, Yuan JX-J, Zhao L, Wang J, Wang Cet al., 2013, MicroRNA expression profile of pulmonary artery smooth muscle cells and the effect of let-7d in chronic thromboembolic pulmonary hypertension, PULMONARY CIRCULATION, Vol: 3, Pages: 654-664, ISSN: 2045-8932

JOURNAL ARTICLE

Li J-F, Lin Y, Yang Y-H, Gan H-L, Liang Y, Liu J, Yang S-Q, Zhang W-J, Cui N, Zhao L, Zhai Z-G, Wang J, Wang Cet al., 2013, Fibrinogen A alpha Thr312Ala Polymorphism Specifically Contributes to Chronic Thromboembolic Pulmonary Hypertension by Increasing Fibrin Resistance, PLOS ONE, Vol: 8, ISSN: 1932-6203

JOURNAL ARTICLE

Zhao L, Chen C-N, Hajji N, Oliver E, Cotroneo E, Wharton J, Wilkins MR, Wang D, Li M, Stenmark KR, McKinsey TA, Buttrick Pet al., 2013, Response to Letter Regarding Article, "Histone Deacetylation Inhibition in Pulmonary Hypertension: Therapeutic Potential of Valproic Acid and Suberoylanilide Hydroxamic Acid", CIRCULATION, Vol: 127, Pages: E540-E540, ISSN: 0009-7322

JOURNAL ARTICLE

Chen C-N, Watson G, Zhao L, 2013, Cyclic guanosine monophosphate signalling pathway in pulmonary arterial hypertension, VASCULAR PHARMACOLOGY, Vol: 58, Pages: 211-218, ISSN: 1537-1891

JOURNAL ARTICLE

Ashek A, Dubois O, Gsell W, Wilkins M, Zhao Let al., 2013, Assessment Of Vascular Remodelling In Pulmonary Arterial Hypertension In Vivo Using 18f-Flurodeoxyglucose Positron Emission Tomography (pet) Imaging, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 187, ISSN: 1073-449X

JOURNAL ARTICLE

Watson G, Oliver E, Zhao L, Wilkins MRet al., 2013, Pulmonary hypertension: old targets revisited (statins, PPARs, beta-blockers)., Pages: 531-548

Pulmonary arterial hypertension is a therapeutic challenge. Despite progress in recent years with three drug classes-prostanoids, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors-long-term patient survival remains poor. Importantly, the introduction and commercial success of these new treatments has been accompanied by growing interest in the pathology of pulmonary hypertension. This, in turn, has stimulated a re-evaluation of the molecular factors driving the structural remodelling of pulmonary arterioles and the opportunities to preserve right ventricular function in pulmonary hypertension. Academics with restricted access to new chemicals have turned to existing drugs to investigate new ideas. It is in this context that the role of statins, peroxisome proliferator-activated receptors (PPARs) and beta-blockers are of interest as potential treatments for pulmonary hypertension.

BOOK CHAPTER

Hameed AG, Arnold ND, Chamberlain J, Pickworth JA, Paiva C, Dawson S, Cross S, Long L, Zhao L, Morrell NW, Crossman DC, Newman CMH, Kiely DG, Francis SE, Lawrie Aet al., 2012, Inhibition of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) reverses experimental pulmonary hypertension, JOURNAL OF EXPERIMENTAL MEDICINE, Vol: 209, Pages: 1919-1935, ISSN: 0022-1007

JOURNAL ARTICLE

Zhao L, Chen C-N, Hajji N, Oliver E, Cotroneo E, Wharton J, Wang D, Li M, McKinsey TA, Stenmark KR, Wilkins MRet al., 2012, Histone Deacetylation Inhibition in Pulmonary Hypertension Therapeutic Potential of Valproic Acid and Suberoylanilide Hydroxamic Acid, CIRCULATION, Vol: 126, Pages: 455-+, ISSN: 0009-7322

JOURNAL ARTICLE

Zeng W-J, Xiong C-M, Zhao L, Shan G-L, Liu Z-H, Xue F, Gu Q, Ni X-H, Zhao Z-H, Cheng X-S, Wilkins MR, He J-Get al., 2012, Atorvastatin in Pulmonary Arterial Hypertension (APATH) study, EUROPEAN RESPIRATORY JOURNAL, Vol: 40, Pages: 67-74, ISSN: 0903-1936

JOURNAL ARTICLE

Nasim MT, Ogo T, Chowdhury HM, Zhao L, Chen C-N, Rhodes C, Trembath RCet al., 2012, BMPR-II deficiency elicits pro-proliferative and anti-apoptotic responses through the activation of TGF-TAK1-MAPK pathways in PAH, HUMAN MOLECULAR GENETICS, Vol: 21, Pages: 2548-2558, ISSN: 0964-6906

JOURNAL ARTICLE

Wojciak-Stothard B, Zhao L, Oliver E, Dubois O, Wu Y, Kardassis D, Vasilaki E, Huang M, Mitchell JA, Louise H, Prendergast GC, Wilkins MRet al., 2012, Role of RhoB in the Regulation of Pulmonary Endothelial and Smooth Muscle Cell Responses to Hypoxia, CIRCULATION RESEARCH, Vol: 110, Pages: 1423-+, ISSN: 0009-7330

JOURNAL ARTICLE

Li Y-Y, Zhai Z-G, Yang Y-H, Pang B-S, Wang H-Y, Zhang W, Zhao L, Wang J, Wang Cet al., 2011, Association of the 894 G > T polymorphism in the endothelial nitric oxide synthase gene with risk of venous thromboembolism in Chinese population, THROMBOSIS RESEARCH, Vol: 127, Pages: 324-327, ISSN: 0049-3848

JOURNAL ARTICLE

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