Dr. Neil Hukriede is a Professor and Vice-Chair in the Department of Developmental Biology, University of Pittsburgh School of Medigine and program director for the Integrative Systems Biology graduate program. He received his Ph.D. from the University of Rochester, Rochester, NY and trained as a National Academy of Sciences Research Associate at the National Institutes of Health, Bethesda, MD.
Acute kidney injury (AKI) is associated with a high mortality and morbidity and AKI survivors often develop end stage renal disease. At present, there are no established therapies to prevent renal injury or accelerate the rate of renal recovery following AKI. The consequences of abnormal kidney function are frequently fatal, with dialysis and organ transplantation the only current long-term treatments for kidney disease. Importantly, the vertebrate kidney has the potential to regenerate, but the molecular mechanisms of kidney regeneration are largely unknown. A better understanding of the processes controlling renal regeneration after injury may provide important clues for the development of new therapies.
The Hukriede lab focuses on two lines of study.
(1) To explore the mechanisms of kidney regeneration we examine damaged kidneys in vivo. Zebrafish transgenic lines reporting injury progression and immune response to injury in larval and adult AKI models are used for real-time image analysis to understand the mechanisms that control renal regeneration. In addition, we use human kidney organoids to model injury and repair.
(2) The Hukriede lab performs chemical screens to identify compounds that could increase the number of renal progenitor cells. A compound identified from one such screen, 4-(phenylthio)butanoic acid (PTBA), was found to expand the expression domains of molecular markers of kidney organogenesis. PTBA exhibits structural and functional similarity to histone deacetylase inhibitors (HDI) and in vitro and in vivo analysis confirmed that PTBA functions as a new HDI, which is selective for HDAC8. Furthermore, studies on PTBA analogue-mediated kidney regeneration in zebrafish, mouse, and human kidney organoid models of AKI have shown compound treatments increase the rate of renal recovery and decrease fibrosis.
Our current studies are focused on confirming HDAC8 as a therapeutic target for promoting
productive repair after AKI, and developing novel HDAC8 inhibitors with improved potency, drug-like properties, and efficacy, that have the potential to advance to clinical trial to treat AKI.