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PhD by Research Programme (Funded Research Programme - Lineage Reprogramming and Organ Regeneration)

Employer
Global Academy Jobs
Location
Singapore
Closing date
Jan 31, 2017

Job Details

Research Project Title: Studying Lineage Reprogramming during Kidney Repair/Regeneration

Principal Investigator: Assistant Professor XIA Yun, LKCMedicine

Project Description:

Kidneys are bilateral organ playing a critical homeostatic role in regulating body fluid composition, waste excretion, and hormone secretion. Adult mammalian kidney parenchyma is comprised of approximately 30 different types of cells, making it one of the most complicated organs inside our body. Given that the number of people suffering from end-stage renal disease (ESRD), a consequence of many conditions including genetic defects, diabetes, cardiovascular diseases, and hypertension, is increasing rapidly, alternative therapeutic methods other than dialysis and kidney transplantation are urgently needed.

The ultimate goal of regenerative medicine is to replace lost or damaged cells, which potentially could be achieved by either extrinsic cell/tissue compensation or intrinsic cell/tissue homeostasis. Mammalian kidney is defined as a non-regenerative organ ascribing to the depletion of embryonic kidney progenitors during 36 weeks gestation in human and neonatal 3-5 days in mouse. Whether residential adult kidney stem cells exist or not is a mystery that has been under many years debating. How to make a non-regenerative organ to regenerate?

Similar to many other non-regenerative organs, adult mammalian kidney has very limited capacity to repair itself. An emerging strategy, referred to as in vivo lineage reprogramming, aims at promoting a tissue’s capability for self-repair either by inducing the proliferation of residual cell or fate conversion of other cell types into the desired cell type. Accumulating evidence indicates that adult mammalian kidney could repair moderate damage through a process involving de-differentiation, proliferation, and re-differentiation of survival cells. In this project, we will employ a reversible mouse acute injury model, kidney ischaemia injury, to interrogate this tissue repair process, during which lineage reprogramming plays essential roles. We would like to identify the cell types presenting strongest survival, proliferation, and repair capacity (referred to as plastic population), and to elucidate whether such capacity has correlation with different develoment stages and age groups. Subsequent genomic and epigenomic profiling of this plastic population will unveil underpinning mechanisms, the activation of which could reinforce in vivo lineage reprogramming to boost self-repair capacity of adult kidney beyond regular physiological range.

If you have questions regarding this project, please email the Principal Investigator, Dr. XIA Yun, at yunxia@ntu.edu.sg

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