In the past year, we have focused on dissemination of information regarding human urinary exosomes and their use in biomarker discovery studies. This has been done through review articles (see publication list below,) and through information provided on our NHLBI DIR website (Google search: Knepper Systems.) We have completed and published work on the interaction between urinary Tamm-Horsfall protein (uromodulin) and urinary exosomes including protocols for eliminating such interactions to achieve quantitative retrieval of exosomes from human urinary samples. We have also maintained our Urinary Exosome Protein Database (http://dir.nhlbi.nih.gov/papers/lkem/exosome/), which has been a useful resource for the renal research community. Ongoing work has focused on development of bioinformatic methods for analysis of biomarker discovery data and application to a dataset obtained by our collaborator, Dr. Serena Bagnasco, obtained from mass spectrometry analysis of urinary exosomes from renal transplant patients with rising creatinine level (in preparation for publication). Relevant publications from the past two years: 2: van Balkom BW, Pisitkun T, Verhaar MC, Knepper MA. Exosomes and the kidney: prospects for diagnosis and therapy of renal diseases. Kidney Int. 2011 Aug 31. doi: 10.1038/ki.2011.292. Epub ahead of print PubMed PMID: 21881557. 10: Gonzales PA, Zhou H, Pisitkun T, Wang NS, Star RA, Knepper MA, Yuen PS. Isolation and purification of exosomes in urine. Methods Mol Biol. 2010;641:89-99. PubMed PMID: 20407943. 13: Fernndez-Llama P, Khositseth S, Gonzales PA, Star RA, Pisitkun T, Knepper MA. Tamm-Horsfall protein and urinary exosome isolation. Kidney Int. 2010 Apr;77(8):736-42. Epub 2010 Feb 3. PubMed PMID: 20130532. 16: Knepper MA, Mindell JA. Structural biology: Molecular coin slots for urea. Nature. 2009 Dec 10;462(7274):733-4. PubMed PMID: 20010678. 20: Knepper MA. Common sense approaches to urinary biomarker study design. J Am Soc Nephrol. 2009 Jun;20(6):1175-8. Epub 2009 May 21. PubMed PMID: 19470673.

Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2012
Total Cost
$74,864
Indirect Cost
Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
City
State
Country
Zip Code
Chen, Lihe; Lee, Jae Wook; Chou, Chung-Lin et al. (2017) Transcriptomes of major renal collecting duct cell types in mouse identified by single-cell RNA-seq. Proc Natl Acad Sci U S A 114:E9989-E9998
Huebner, Alyssa R; Cheng, Lei; Somparn, Poorichaya et al. (2016) Deubiquitylation of Protein Cargo Is Not an Essential Step in Exosome Formation. Mol Cell Proteomics 15:1556-71
Knepper, Mark A; Kwon, Tae-Hwan; Nielsen, Soren (2015) Molecular Physiology of Water Balance. N Engl J Med 373:196
Knepper, Mark A; Kwon, Tae-Hwan; Nielsen, Soren (2015) Molecular physiology of water balance. N Engl J Med 372:1349-58
Pisitkun, Trairak; Dummer, Patrick; Somparn, Poorichaya et al. (2014) Integrated Design of Antibodies for Systems Biology Using Ab Designer. J Proteomics Bioinform 7:088-94
Yu, Panpan; Pisitkun, Trairak; Wang, Guanghui et al. (2013) Global analysis of neuronal phosphoproteome regulation by chondroitin sulfate proteoglycans. PLoS One 8:e59285
Miller, R Lance; Sandoval, Pablo C; Pisitkun, Trairak et al. (2013) Vasopressin inhibits apoptosis in renal collecting duct cells. Am J Physiol Renal Physiol 304:F177-88
Wilson, Justin L L; Miranda, Carlos A; Knepper, Mark A (2013) Vasopressin and the regulation of aquaporin-2. Clin Exp Nephrol 17:751-64
Knepper, Mark A; Miranda, Carlos A (2013) Urea channel inhibitors: a new functional class of aquaretics. Kidney Int 83:991-3
Jensen, Thomas B; Pisitkun, Trairak; Hoffert, Jason D et al. (2012) Assessment of the effect of 24-hour aldosterone administration on protein abundance in fluorescence-sorted mouse distal renal tubules by mass spectrometry. Nephron Physiol 121:p9-15

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