Education & Training
- Ph.D. in Developmental Genetics from University Rochester, Rochester, NY, 1997
- M.S. in Biology from University Rochester, Rochester, NY 1993
- B.S. in Biology from Minnesota State University Moorehead, Moorehead, MN, 1991
Research Interest Summary
Research Categories
Research Interests
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 (lhx1a, pax2a, pax8, wt1a/b, NakATPase, chd17, RARE, FUCCI) and lines (LyzC, MPEG) that follow the 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 vitro and 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.
Representative Publications
de Groh, E.D., Swanhart, L.M., Cianciolo Cosentino, C., Jackson, R.L., Dai, W., Kitchens, C.A., Day, B.W., Smithgall, T.E. and N.A. Hukriede (2010) Inhibition of Histone Deacetylase Expands the Renal Progenitor Cell Population. JASN 21, 794-802. PMCID: PMC2871303
Diep, C.Q., Ma, D., Arora, N., Wingert, R.A., Bollig, F., Djordjevic, G., Lichman, B., Zhu, H., Ikenaga, T., Ono, F., Englert, C., Hukriede, N.A., Handin, R.I., and A.J. Davidson (2011) Identification of adult renal progenitor cells capable of nephron formation and regeneration in zebrafish. Nature Feb 3;470(7332), 95-100. PMCID: PMC3170921
Cirio, M.C., Zhao, H., Haldin, C.E., Cianciolo Cosentino, C., Stuckenholz, C., Chen, X., Hong, S-K, Dawid, I.B. and N.A. Hukriede (2011) Lhx1 is required for specification of the renal progenitor cell field. PLOS ONE Apr 15; 6(4):e18858. PMCID: PMC3078140
Cianciolo Cosentino C, Skrypnyk, N., Brilli L.B., Chiba, T., Novitskaya, T., Woods, C., West, J., Korotchenko, V.N., McDermott, L., Day, B.W., Davidson A.J., Harris, R., de Caestecker, M.P., and N.A. Hukriede (2013) Histone Deacetylase inhibitor enhances recovery after AKI. JASN May 26(6), 943-53. PMCID: PMC3665399
Sanker, S., Cirio, M.C., Vollmer, L.L., Goldberg, N.D., McDermott, L.A., Hukriede, N.A., and A. Vogt (2013) Development of high-content assay for kidney progenitor cell expansion in transgenic zebrafish. J. BioMol. Screen. Dec;18(10):1193-202. PMCID: PMC3830658
Novitskaya, T., McDermott, L., Zhang, K.X., Paueksakon, P., Hukriede, N.A., and M.P. de Caestecker (2014) A PTBA class small molecule enhances recovery and reduces post injury fibrosis after aristolochic acid-induced kidney injury. AJP-Renal Mar;306(5):F496-504. PMCID: PMC3949031
Chiba, T, Skrypnyk, N., Brilli Skvarca, L, Penchey, R., Zhang, K.X., Rochon, E.R., Fall, J.L., Paueksakon, P., Yang, H., Roman, B.L., Zhang, M-Z., Harris, R., Hukriede, N.A., and M.P. de Caestecker (2015) Retinoic Acid Signaling Coordinates Macrophage-Dependent Injury and Repair after Acute Kidney Injury. JASN Jun 24. pii: ASN.2014111108. PMCID: PMC4731115
Skrypnyk, N. I., Sanker, S., Brilli Skvarca, L., Woods, C., Chiba, T., Patel, K., Goldberg, N. D., McDermott, L., Vinson, P. N., Calcutt, M. W., Vernetti, L. A., Vogt, A., Huryn, D. M., Hukriede, N. A., and M. P. de Caestecker. (2016) Delayed treatment with PTBA analogues reduces post injury renal fibrosis after kidney injury. AJP- Renal Physiology 310: F705-16. (Epub Dec. 9, 2015). PMCID: PMC4835925
Naylor R.A., Brilli Skvarca L, Thisse C, Thisse, Hukriede N.A., and Davidson AJ. (2016) The anterior–posterior axis of the non-axial mesoderm aligns with the classic dorsal-ventral axis and is sequentially patterned by the BMP and RA pathways. Nature Comm. Jul 13;7:12197. PMCID: PMC4947171