Research Focus Areas:
Dr. Zhang's research interests concentrated on cardiovascular remodeling and signaling pathway cascades in response to hemodynamic stress, with a particular focus on cellular functions and the underlying regulatory mechanisms. The long-term goal of Dr. Zhang's studies is to advance understanding of the signaling mechanisms that determine cardiopulmonary function and may provide new opportunities for treatment and prevention of various cardiopulmonary diseases. Dr. Zhang utilizes both in vitro and in vivo models in his research along with gene manipulation approaches and analytical techniques.
Dr. Zhang's laboratory has the following research programs with the aims to identify novel therapeutic targets to improve lung and heart function.
- Pulmonary arterial hypertension (PAH) is a devastating disease, which is associated with poor prognosis related to right ventricular (RV) dysfunction and RV failure. While RV failure is the main cause of death in patients with PAH, the underlying mechanisms of RV dysfunction/failure in PAH remain unclear and no RV targeted therapies are available. The goal of this research program is to identify novel therapeutic targets to improve RV function by mitigating mitochondrial dysfunction and improving mitochondrial bioenergetics in the RV cardiomyocytes in PAH.
- MicroRNAs are identified as essential regulatory molecules in both cardiac and pulmonary diseases. The goal of this research program is to identify novel disease-related microRNAs and to investigate their expression, regulation, and functional role in regulating cardiopulmonary diseases including PAH.
Dr. Zhang's laboratory has the expertise in:
- DNA, RNA, and protein extraction and analysis from cultured cells and tissues
- Histology, immunohistochemistry, and immunofluorescence on frozen or paraffin-embedded tissue sections
- Subcellular signal and target identification and studying mitochondrial morphology, function, and their regulation
- Mitochondrial functional assessments using high-resolution O2K FluoRespirometer (Oroboros) and Seahorse XF Analyzers
- Bacterial culture and molecular cloning, site-directed mutagenesis, and subsequent applications for gene manipulations and protein production
- Stable cell line development, including clone screening, selection, and stability
- Diverse cell culture models, including cell lines, primary neonatal and adult cardiac myocytes and fibroblasts, and pulmonary endothelial cells
- Gene manipulations and cell-based assays in cell lines and primary mammalian cells
- Generation of in vivo disease models
- Transgenic model generation (from cloning to injectable transgenic constructs), genotyping, validation, and phenotype characterization
- Cardiac function assessments using echocardiography and in vivo hemodynamic measurements
Current Research Funding:
Title: Role of Endothelial Anoctamin-1 in Pulmonary Artery Hypertension
Grant/Source: R01, NIH/NHLBI (PI: Dr. Choudhary)
Date: 07/01/2019 – 06/30/2023
Role: Research Biologist (Since Dr. Zhang was recruited to Providence VA Medical Center/Ocean State Research Institute in January 2020, he has been collaborating with Dr. Choudhary for assessments of mitochondrial function and signaling transduction for this project)
Past Research Funding:
Title: Effects of LCZ696 on cardiac function and remodeling response to chronic pressure overload
Grant/Source: Novartis/Preclinical Study
Date: 03/01/2016 – 1/31/2019
Title: Regulation of cardiac fibroblast function by microRNAs
Grant/Source: NIH, COBRE for CardioPulmonary Vascular Biology (PI: Dr. Rounds)
Date: 09/20/2013 – 05/31/2018
Role: Targeted Project PI
Title: Regulation of Cardiac Fibroblast Function by MicroRNAs
Grant/Source: American Heart Association, Scientist Development Grant (National Center)
Dates: 1/1/2013 - 12/31/2016
* This AHA grant was relinquished on 9/16/2013 to accept a Targeted Investigator Project in NIH “COBRE for CardioPulmonary Vascular Biology” (P20 GM103652, PI: Dr. Rounds).
- Vang A, da Silva Goncalves Bos D, Fernandez-Nicolas A, Zhang P, Morrison A, Mancini T, Clements RT, Polina I, Cypress MW, Jhun BS, Hawrot E, Mende U, O-Uchi J, Choudhary G. ⍺7 nicotinic acetylcholine receptor mediates right ventricular fibrosis and diastolic dysfunction in pulmonary hypertension. JCI Insight. 2021 May 11;142945.
- Valkov N, King ME, Moeller J, Liu H, Li X, Zhang P. MicroRNA-1-mediated inhibition of cardiac fibroblast proliferation through targeting cyclin D2 and CDK6. Front. Cardiovasc. Med., 2019 May;6:65.
- Yao H, Gong J, Peterson AL, Lu X, Zhang P, Dennery PA Fatty acid oxidation protects against hyperoxia-induced endothelial cell apoptosis and lung injury in neonatal mice. Am J Respir Cell Mol Biol. 2019 Jun;60(6):667-677.
- Chorzalska A, Ahsan N, Rao RSP, Roder K, Yu X, Morgan J, Tepper A, Hines S, Zhang P, Treaba DO, Zhao TC, Olszewski AJ, Reagan J, Liang O, Gruppuso PA, Dubielecka PM. Overexpression of Tpl2 is linked to imatinib resistance and activation of MEK-ERK and NF-κB pathways in a model of Chronic Myeloid Leukemia. Mol Oncol. 2018 May;12(5):630-647.
- Vang A, Clements RT, Chichger H, Kue N, Allawzi A, O'Connell KA, Jeong EM, Dudley S Jr, Sakhatskyy P, Lu Q, Zhang P, Rounds S, Choudhary G. Effect of α7 nicotinic acetylcholine receptor activation on cardiac fibroblasts: A mechanism underlying RV fibrosis associated with cigarette smoke exposure. Am J Physiol Lung Cell Mol Physiol. 2017; 312(5):L748-L759.
- Zhang P, Kofron CM, Mende U. Heterotrimeric G protein-mediated signaling and its non-canonical regulation in the heart. Life Sci. 2015; 129:35-41.
- Chichger H, Vang A, O'Connell K, Zhang P, Mende U, Harrington E, Choudhary G. PKC δ and βII regulate angiotensin II mediated fibrosis through p38: a mechanism of RV fibrosis in pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2015; 308(8):L827-836.
- Zhang P, Mende U. Functional role, mechanisms of regulation and therapeutic potential of Regulator of G protein Signaling 2 in the heart. Trends Cardiovasc Med. 2014; 24(2): 85-93.
- Zhang P, Su J, Mende U. Cross-talk between cardiac myocytes and fibroblasts: from multi-scale investigative approaches to mechanisms and functional consequences. Am J Physiol Heart Circ Phys. 2012; 303(12): H1385-1396.
- Park-Windhol C, Zhang P, Zhu M, Su J, Chaves L, Maldonado Lopez A, King ME, Rickey L, Cullen D, and Mende U. Gq/11-mediated signaling and hypertrophy in mice with cardiac-specific transgenic expression of regulator of G-protein signaling 2. PLoS One 2012; 7(7): e40048.
- Desroches BR*, Zhang P*, Choi B, Maldonado AE, Rago A, Liu G, Nath N, King ME, Yang B, Koren G, Morgan JR, Mende U. Functional scaffold-free 3D cardiac microtissues: a novel model for the investigation of heart cells. Am J Physiol Heart Circ Physiol 2012; 302(10): H2031-2042. * with equal contributions
- Zhang P, Mende U. Regulators of G protein signaling in the heart and their potential as therapeutic targets. Circ Res 2011; 109: 320-333.
- Zhang P*, Su J, King ME, Maldonado AE, Park C, and Mende U. Regulator of G Protein Signaling 2 is a functionally important negative regulator of Angiotensin II-induced cardiac fibroblast responses. Am J Physiol Heart Circ Phys 2011; 301: H147-156. * Corresponding author An image from this paper has been selected as cover image for AJP-Heart and Circulatory Physiology for 6 issues (from July 2011 to December 2011).
Zhang Lab Members & Trainees