Research Project 3 – KIDNEY

Intercepting Renal Damage Following Skin Exposure to Arsenicals

This project is based on findings that cutaneous exposure to lewisite not only damages the skin but is also rapidly absorbed and exerts toxic effects in the kidney leading to both acute and delayed kidney damage.  A research team led by Dr. Anupam Agarwal found that arsenicals cause epigenetic histone remodeling by hyperacetylation and recruitment of BRD4 to promotor regions of inducible genes associated with inflammation and tissue damage.  Therefore, the overall goal of this project will be to develop mechanism-based post-exposure countermeasures that can mitigate arsenical-induced kidney damage. 

The aims of this project are:

1. To characterize an arsenical mediated murine model of acute kidney injury (AKI) to determine the dose- and time-dependence of kidney damage.
2. To determine the mechanisms by which arsenicals cause AKI (focusing on BRD4 and HO-1 for intervention in arsenicals-induced AKI.)
3. To develop a targeted therapeutic intervention in arsenical-induced AKI and to determine the optimal window for the beneficial effects by post-exposure treatment to arsenicals.

Successful completion of this research will not only provide an antidote for chemical injury but will also contribute to a broader understanding of how endogenous responses can be exploited towards developing new therapeutic strategies for acute kidney injury.