Currently at Duke University
The goal of my research is to study the molecular mechanisms of nephrotic syndrome and podocyte regeneration using zebrafish mesonephros (adult fish kidney) as a new model system. Specifically, I have successfully generated a transgenic zebrafish model of inducible podocyte injury, which can mimic human nephrotic phenotypes in adult zebrafish, and have established a new transgene-based functional assay for zebrafish renal glomerular barrier. I will apply these transgenic models that I have established for high-throughput screenings for therapeutical chemical compounds that protect podocytes from damages, study podocyte regeneration, and isolate novel nephrotic zebrafish mutants. I have had more than 10 years of training and research experience in zebrafish development and genetics since I entered the Rackham Graduate School at the University of Michigan in the year 2000. During my post-graduate training, I have participated in the study of genes regulating the development of the nervous system in zebrafish embryos and completed my doctoral dissertation on the characterization of two zebrafish mutants, relaxed and non-active. I was also involved in a forward genetic screening for mutants affecting zebrafish motor behaviors. Thus, I have accumulated experience on zebrafish mutant screening and positional cloning. After receiving my PhD degree I joined Dr Hildebrandt‰Ûªs lab, focusing on developing zebrafish models of pediatric kidney diseases using transgenesis and targeted gene lesion or gene-knockdown. I have characterized in zebrafish the function of Nephrocystin-3, a ciliopathy-related gene responsible for juvenile nephronophthisis (Zhou et al. AJP Renal Physiol. 2010); SDCCAG8, a gene responsible for retinal-renal ciliopathy (Otto et al. Nat Genetics. 2011); and COQ6, mutations of which causes nephrotic syndrome and sensory deafness (Heeringa et al. JCI. 2011). I have also participated in a number of projects studying human genetics of nephronophthisis and nephrotic syndrome.
Zhou W*, Otto EA*, Cluckey A, Airik R, Hurd TW, Chaki M, and 32 authors. FAN1 mutations cause karyomegalic interstitial nephritis, linking chronic renal failure to DNA damage response signaling. Nat Genet. 2012.(*These authors contributed equally to this work)
Chaki M, Airik R, Ghosh A, Giles R, Chen R, Slaats G, Wang H, Hurd T; Zhou W, Cluckey A, Gee HY, and 60 authors, Levy S, Smogorzewska A, Otto EA, Hildebrandt F. Exome capture reveals ZNF423 and CEP164 mutations, linking renal ciliopathies to DNA damage. Cell, 2012
Zhou W*, Hildebrandt F. Inducible Podocyte Injury and Proteinuria in Transgenic Zebrafish. J Am Soc Nephrol. 2012 Mar 22. (* Corresponding author)
Heeringa SF*, Chernin G*, Chaki M, Zhou W, Sloan AJ, Ji Z, Xie LX, Salviati L, Hurd TW, Vega-Warner V, et al. COQ6 mutations cause nephrotic syndrome with sensorineural deafness in humans, concurrent with increased apoptosis. J Clin Invest. 121(5):2013-24, 2011. PMID:21540551 (*These authors contributed equally to this work)
Zhou W, Boucher RC, Bollig F, Englert C, Hildebrandt F. Characterization of mesonephric development and regeneration using transgenic zebrafish. Am J Physiol Renal Physiol. 299(5):F1040-7, 2010. PMID: 20810610