About the Project
With the significant and growing healthcare burden caused by chronic heart failure, the ability to develop new directions for treatment, reducing or preventing the worsening of disease, would be of great value. Since the discovery of endogenous cardiac stem cells (eCSCs) by Beltrami et al. in 2003 (Cell 114(6):763-776), followed by definitive evidence of human cardiac renewal throughout life (Bergmann et al. (2009) Science 324(5923):98-102), there has been keen interest in determining what role(s) these cells play in cardiac regeneration and repair.
Much interest to date has focused closely on their ability to form cardiac myocytes, however eCSCs are also capable of generating vascular cell types (endothelial and smooth muscle cells), offering the ability to generate new blood vessels within the heart. However, another important aspect of eCSC biology is their ability to generate and release a powerful ‘secretome’, allowing beneficial impact on cells via paracrine actions. This is believed to be the underlying cause of the significant improvement in heart function seen when eCSCs were delivered in clinical trials to patients, after cardiac damage from heart attack (Hong and Bolli (2014) Curr. Treat. Options Cardiovasc. Med. 16(7):324).
This project will examine the role played by receptor tyrosine kinases (RTKs) on the promotion of eCSC secretome generation, and in governing the ability of eCSCs to form vascular cell lineages. We will also investigate the impact of RTK inhibitors, drugs with known cardiotoxicity, on secretome generation and release.
Funding Notes
The PhD will start when a suitable applicant is selected and funding confirmed. Applicants should have, or be expecting to receive, a 2.1 Hons degree (or equivalent) or above in a relevant subject. The funding is open to international students (subject to eligibility); self-funded students, or those with funding already available and seeking a suitable research project, are encouraged to apply. For further details, please contact Dr. Smith ([Email Address Removed]).
References
Ellison GM, Vicinanza C, Smith AJ, Aquila I, Leone A, et al. Adult c-kitpos Cardiac Stem Cells Are Necessary and Sufficient for Functional Cardiac Regeneration and Repair. Cell 154(4), 827-42 (2013).
Smith AJ, Lewis FC, Aquila I, Waring CD, Agosti V, et al. Isolation and characterisation of resident endogenous c-kit-positive cardiac stem cells (eCSCs) from the adult mouse and rat heart. Nat. Prot. 9(7): 1662-1681 (2014).
Vicinanza C, Aquila I, Scalise M, Cristiano F, Marino F, Cianflore E, Mancuso T, Marotta P, Sacco W, Lewis FC, Couch L, Shone V, Gritti G, Torella A, Smith AJ, Terracciano CMN, Britti D, Veltri P, Indolfi C, Nadal-Ginard B, Ellison-Hughes GM, Torella D (2017) Adult cardiac stem cells are multipotent and robustly myogenic: c-kit expression is necessary but not sufficient for their identification. Cell Death and Differentiation doi: 10.1038/cdd.2017.130. (Epub ahead of print)
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