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Member Profile



Mark P. de Caestecker

Personal Information
Title Professor
Expertise None Selected
Institution Vanderbilt University
Data Summary
TypeCount
Grants/SubContracts 2
Progress Reports 1
Publications 2
Protocols 0
Committees 0
Experiments 0
Strains 0
Models 0

SubContract(s)


Retinoic acid signaling and regeneration of damaged nephrons post AKI
There is increasing evidence that incomplete repair of damaged nephrons after episodes of acute kidney injury (AKI), plays an important role in accelerating chronic kidney disease (CKD) in the patients with diabetic nephropathy. However, the intrinsic mechanisms regulating regenerative repair of damaged nephrons is poorly understood. Retinoic acid (RA) signaling plays an essential role in initiating progenitor cell expansion during organ and appendage regeneration in zebrafish, but the role of this pathway in mediating nephron repair is currently unknown. We have shown that RA signaling is activated in the kidney after AKI, and that RA signaling increases repair and decreases post injury fibrosis after AKI. We have also shown that Raldh2 and Rdh10, enzymes that are required for conversion retinol to active RA metabolites, are rapidly induced in peri-tubular fibroblasts after AKI, and that expression is regulated oxidative stress and TGF-ß. The goal of these studies is to use in vitro and in vivo models to understand how RA synthesis is regulated by oxidative stress after AKI, and to provide evidence that fibroblast-derived RA acts as a paracrine signaling factor to promote a program of regenerative repair of damaged nephron segments after AKI. By understanding the cellular cues triggering RA synthesis by peri-tubular fibroblasts after AKI, in the long term we anticipate that these studies will enable us to design approaches to modulate this response and enhance post AKI repair.

Use of a novel PTBA analogue to ameliorate CKD progression after AKI in experimental diabetic nephropathy
The goal of these studies is to evaluate the effects of short-term treatment with a novel class of HDAC inhibitors on long-term chronic kidney disease (CKD) progression after acute kidney injury (AKI) in experimental diabetic nephropathy (DN). Studies are part of an on-going collaborative research program with Neil Hukriede from Pittsburgh, to develop novel therapeutics that reduce post-AKI fibrosis and are effective when administered late after the initiating injury. The specific focus of this pilot project is to determine whether our lead agent, UPHD186, is effective in preventing post AKI fibrosis and progressive CKD in the context of both mild and severe experimental DN, in order to define potential therapeutic applications of this agent.


Progress Reports

Annual Reports

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