Neil Hukriede, Ph.D.

  • Professor and Vice Chair
  • Director, Integrative System Biology

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.

Education & Training

  • B.A. - Minnesota State University, Moorhead MN 1987-1991
  • Ph.D. - University of Rochester, Rochester NY 1991-1998
  • Post-doc - National Institutes of Health, Igor Dawid, Bethesda MD 1998-2003

Representative Publications

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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. PMCID: PMC4835925
  7. Wen, W., Cui, L., Morrisroe, S., Maberry, D., Emlet., D., Watkins, S., Hukriede, N.A., Kellum, J. (2018) A zebrafish larvae model to study the role of innate immunity in septic acute kidney injury. AJP-Renal Physiology Aug 1:315(2):F291-299. PMCID: PMC6139521
  8. Espiritu, E., Bais, A., Hochbaum, D., Phua, Y.L., Butterworth, M.B., Goto, T., Ho., J Hukriede, N.A. and M.C. Cirio, (2018) The Lhx1-Ldb1 complex interacts with Furry to regulate microRNA expression during pronephric kidney development.Sci. Reports Oct. 30; 8(1): 16029. PMCID: PMC6207768
  9. Brilli Skvarca, L., Han, H.I, Missinato, M.A., Espiritu, E., Rochon, E.R., McDaniels, M.D., Roman, B.L., Waxman, J.S., Watkins, S., Davidson, A.J., Tsang, M., and Hukriede, N.A., (2019)Enhancing acute kidney injury regeneration by promoting cellular dedifferentiation in zebrafish. Disease Models and Mech. Apr 5;12(4). pii: dmm037390. doi: 10.1242/dmm.037390.

Research Interest Summary

Kidney Regeneration and Therapeutics

Research Grants

R01 DK069403

Elucidating the cellular mechanisms of a pro-regenerative drug therapy for acute kidney injury

DoD W81XWH-17-1-0610

Optimizing Small Molecule Therapeutics for Diabetic Kidney Disease and Acute Kidney Injury

R01 DK112652

High content in vivo screening for acute kidney injury ameliorating drugs

R01 DK104287

Role of uroplakins in urinary tract development and CAKUT

P30 DK079307

Pittsburgh Center for Kidney Research

New Zealand Health Research Council

Kidney Organoids: Modeling kidney injury and preclinical drug testing