University of Pittsburgh Department of Cell Biology
    • Neil Hukriede, Ph.D.

    Neil Hukriede, Ph.D.

    Director, Center for Integrative Organ Systems (cenIOS)
    Tel: 412-383-2211
    Address: 5061 BST3
    3501 Fifth Avenue
    Pittsburgh, PA 15213
  • Research

    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 themolecular 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 kidneysin vivo. Zebrafish transgenic lines reporting injury progressionand 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. (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 vitroand in vivo analysis confirmed that PTBA functions as a new HDI. Furthermore, studies on PTBA analogue-mediated kidney regeneration in zebrafish and mouse models of AKI have shown compound treatments increase the rate of renal recovery and decrease fibrosis. These findings validate our strategy that discoveries using the zebrafish model are directly translatable to mammalian models of AKI.

  • Publications

    1. Maggiore JC, LeGraw R, Przepiorski A, Velazquez J, Chaney C, Streeter E, Silva-Barbosa A, Franks J, Hislop J, Hill A, Wu H, Pfister K, Howden SE, Watkins SC, Little M, Humphreys BD, Watson A, Stolz DB, Kiani S, Davidson AJ, Carroll TJ, Cleaver O, Sims-Lucas S, Ebrahimkhani MR, Hukriede NA. Genetically engineering endothelial niche in human kidney organoids enables multilineage maturation, vascularization and de novo cell types.. bioRxiv. 2023 May 30;():. pii: 2023.05.30.542848. doi: 10.1101/2023.05.30.542848. PubMed PMID: 37333155;
    2. Hukriede NA, Soranno DE, Sander V, Perreau T, Starr MC, Yuen PST, Siskind LJ, Hutchens MP, Davidson AJ, Burmeister DM, Faubel S, de Caestecker MP. Experimental models of acute kidney injury for translational research.. Nat Rev Nephrol. 2022 May;18(5):277-293. doi: 10.1038/s41581-022-00539-2. PubMed PMID: 35173348;
    3. de Caestecker MP, Siew ED, Harris RC, Hukriede NA. Introduction: The 2019 Federation of American Societies for Experimental Biology Acute Kidney Injury From Bench to Bedside Conference.. Semin Nephrol. 2020 Mar;40(2):99-100. doi: 10.1016/j.semnephrol.2020.01.001. PubMed PMID: 32303287;


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