Epithelial Systems Biology Laboratory

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Kidney Systems Biology Project

The Epithelial Systems Biology Laboratory (ESBL) is utilizing next-generation DNA sequencing and protein mass spectrometry to investigate vasopressin signaling and transcriptional regulation in the renal collecting duct. The resulting data sets are made freely available to all investigators via web resources assessible here. Opportunities exist for postdoctoral fellows who wish to learn these techniques and associated bioinformatic approaches.

References:

  1. Sung CC, Chen L, Limbutara K, Jung HJ, Gilmer GG, Yang CR, Lin SH, Khositseth S, Chou CL, Knepper MA. RNA-Seq and protein mass spectrometry in microdissected kidney tubules reveal signaling processes initiating lithium-induced nephrogenic diabetes insipidus. Kidney Int. 2019; S0085-2538 30267-4 PMID: 31146973.

  2. Rinschen MM, Limbutara K, Knepper MA, Payne DM, Pisitkun T. From Molecules to Mechanisms: Functional Proteomics and Its Application to Renal Tubule Physiology. Physiol Rev. 2018; 98:2571-2606. PMID: 30182799.

  3. Jung HJ, Raghuram V, Lee JW, Knepper MA. Genome-Wide Mapping of DNA Accessibility and Binding Sites for CREB and C/EBPβ in Vasopressin-Sensitive Collecting Duct Cells. J Am Soc Nephrol. 2018; 29:1490-1500. PMID: 29572403.

  4. Lee JW, Alsady M, Chou CL, de Groot T, Deen PMT, Knepper MA, Ecelbarger CM. Single-tubule RNA-Seq uncovers signaling mechanisms that defend against hyponatremia in SIADH. Kidney Int. 2018; 93:128-146. PMID: 28843412.

  5. Isobe K, Jung HJ, Yang CR, Claxton J, Sandoval P, Burg MB, Raghuram V, Knepper MA. Systems-level identification of PKA-dependent signaling in epithelial cells. Proc Natl Acad Sci USA. 2017; 114:E8875-E8884. PMID: 28973931.

  6. Chen L, Lee JW, Chou CL, Nair AV, Battistone MA, Paunescu TG, Merkulova M, Breton S, Verlander JW, Wall SM, Brown D, Burg MB, Knepper MA. Transcriptomes of major renal collecting duct cell types in mouse identified by single-cell RNA-seq. Proc Natl Acad Sci USA. 2017; 114:E9989-E9998. PMID: 29089413.

  7. LeMaire SM, Raghuram V, Grady CR, Pickering CM, Chou CL, Umejiego EN, Knepper MA. Serine/threonine phosphatases and aquaporin-2 regulation in renal collecting duct. Am J Physiol Renal Physiol. 2017; 312:F84-F95. PMID: 27784696.

  8. Corcoran CC, Grady CR, Pisitkun T, Parulekar J, Knepper MA. From 20th century metabolic wall charts to 21st century systems biology: database of mammalian metabolic enzymes. Am J Physiol Renal Physiol. 2017; 312:F533-F542. PMID: 27974320.

  9. Sandoval PC, Claxton JS, Lee JW, Saeed F, Hoffert JD, Knepper MA. Systems-level analysis reveals selective regulation of Aqp2 gene expression by vasopressin. Sci Rep. 2016; 6:34863. PMID: 27725713.

  10. Lee JW, Chou CL, Knepper MA. Deep sequencing in microdissected renal tubules identifies nephron segment-specific transcriptomes. J Am Soc Nephrol. 2015; 26: 2669-77. PMID: 25817355.

  11. Knepper MA. Systems biology of diuretic resistance. J Clin Invest. 2015; 125: 1793-5. PMID: 25893597.

  12. Bradford D, Raghuram V, Wilson JL, Chou CL, Hoffert JD, Knepper MA, Pisitkun T. Use of LC-MS/MS and Bayes' theorem to identify protein kinases that phosphorylate aquaporin-2 at Ser256. Am J Physiol Cell Physiol. 2014; 307: C123-39. PMID: 24598363.

  13. Sanghi A, Zaringhalam M, Corcoran CC, Saeed F, Hoffert JD, Sandoval P, Pisitkun T, Knepper MA. A knowledge base of vasopressin actions in the kidney. Am J Physiol Renal Physiol. 2014; 307: F747-55. PMID: 25056354.

  14. Huling JC, Pisitkun T, Song JH, Yu MJ, Hoffert JD, Knepper MA. Gene expression databases for kidney epithelial cells. Am J Physiol Renal Physiol. 2012; 302: F401-7. PMID: 22114206.

  15. Knepper MA. Systems biology in physiology: the vasopressin signaling network in kidney. Am J Physiol Cell Physiol. 2012; 303: C1115-24. PMID: 22932685.