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(A*STAR) Investigating Pak2 regulation of extracellular matrix after myocardial infarction

  • Full or part time
  • Application Deadline
    Friday, January 31, 2020
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Following myocardial infarction (MI), extracellular matrix (ECM) remodelling is critical for acute cardiac tissue healing; however, excessive accumulation of ECM during the chronic stage accelerates the progression to heart failure. In our pilot study, we observed that loss of p21 protein activated kinase-2 (Pak2) disposed the mice more vulnerable to myocardial infarction. In this PhD project, we will 1) Generate the mice with Pak2 knockout in myofibroblasts; 2) Characterise how Pak2 knockout in myofibroblasts impacts ECM remodelling after MI; 3) Investigate molecular mechanism whereby Pak2 regulates ECM composition and remodelling following MI. Obtained data will provide new insights in developing novel treatment strategies for MI through targeting Pak2.

Entry Requirements:
Applications should be submitted online and candidates should make direct contact with the Manchester supervisor to discuss their application directly. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

Funding Notes

This project is available to UK/EU candidates. Funding covers fees (UK/EU rate) and stipend for four years. Overseas candidates can apply providing they can pay the difference in fees and are from an eligible country. Candidates will be required to split their time between Manchester and Singapore, as outlined on View Website.

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

1. Binder P, Wang S, Radu M, Zin M, Collins L, Khan S, Li Y, Sekeres K, Humphreys N, Swanton E, Reid A, Oceandy D, Guan K, Müller OJ, Cartwright EJ, Chernoff J, Wang X*, Liu W*. (2019). Pak2 as a novel therapeutic target for cardioprotective endoplasmic reticulum stress response. Circ Res. 124(5):696-711. 9 (Co-corresponding author)
2. Wei Liu, Andrea Ruiz, Shou-bao Wang, Saba Khan, Min Zi, Jing Guo, Gina Galli, Elizabeth Cartwright, Xin Wang. Mitochondrial dysfunction from the loss of extracellular signal-regulated protein kinase 5 in metabolic stress-induced cardiomyopathy. Nature Commun. 2017 Sep 8;8(1):494.
3. Sanjoy K. Chowdhury, Wei Liu, Min Zi, Hoyee Tsui, Shunyao Wang, Simon Castro, Sukhpal Prehar, Yong Ji, Catherine B. Millar, Ming Lei, Xiuqin Zhang, Ruiping Xiao, Henggui Zhang, Mark R. Boyett, Elizabeth. J. Cartwright, Holly A. Shiels, Xin Wang. Stress-activated kinase MKK7 governs epigenetics of cardiac repolarisation for arrhythmia prevention. Circulation. 2017;135:683-699.
4. Riham Abou-Leisa, Tamer M. A. Mohamed, Nicholas Stafford, Arfa Maqsood, Min Zi, Sukhpal Prehar, Florence Baudoin-Stanley, Xin Wang, Elizabeth J. Cartwright, Ludwig Neyses, Delvac Oceandy. The Plasma Membrane Calcium ATPase 4 Signaling in Cardiac Fibroblasts Mediates Cardiomyocyte Hypertrophy. Nat Commun. 2016 Mar 29;7:1107.
5. Tsui H, Zi M, Wang S, Chowdhury SK, Prehar S, Liang Q, Cartwright EJ, Lei M, Liu W, Wang X. Smad3 Couples Pak1 With the Antihypertrophic Pathway Through the E3 Ubiquitin Ligase, Fbxo32. Hypertension. 2015 Dec;66(6):1176-83.

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