The mentor, Mark Knepper, M.D., Ph.D., is a Biomedical Engineer who uses systems biology-based approaches to study how the kidney regulates water excretion. This involves use of large-scale data acquisition techniques, such as protein mass spectrometry and 'next-generation' nucleotide sequencing technologies to discover molecular mechanisms involved in renal water transport. Much of the focus is on regulation of molecular water channels called "aquaporins" by the hormone vasopressin. The Epithelial Systems Biology Laboratory is a small close-knit group of scientists devoted to development and exploitation of cutting-edge experimental and computational tools for these studies.
The objective is to carry out an experimental study that the student can pursue independently of other ongoing laboratory studies, generating a publication with the BESIP student as first author. The current opportunity for a BESIP student is in the category of proteomics in renal physiology. The student will use protein mass spectrometry to identify the mechanism of lithium-induced diabetes insipidus. Lithium salts are used to treat a neuro-psychiatric disease called 'bipolar disorder', but cause a defect that blocks water transport in kidney collecting duct cells, preventing the concentration of urine. The goal is to identify the mechanism of this defect by discovering proteins that are altered in abundance. The student will learn basic biochemical techniques and the principles of protein mass spectrometry. He/she will also learn about strategies for bioinformatic analysis of mass spectrometry data. The student will be closely supervised by the mentor to assure rapid progress with the goal of preparing and publishing a paper based on his/her data.
Recent papers by BME students (Sachs, Harbaugh, Zhao, Huling, Liu, Claxton, Corcoran, Grady) and ChE students (Jacob, Feric, Sanghi, Pickering) in the lab include:
- Sachs AN, Pisitkun T, Hoffert, JD, Yu MJ, Knepper MA. LC-MS/MS analysis of differential centrifugation fractions from native inner medullary collecting duct of rat. Am J Physiol Renal Physiol, 2008; 295: F 1799-806.
- Jacob VA, Harbaugh CM, Dietz JR Fenton RA, Kim SM, Castrop H, Schnermann J, Knepper MA, Chou CL, Anderson SA. Magnetic resonance imaging of urea transporter knockout mice shows renal pelvic abnormalities. Kidney Int., 2008; 74: 1202-8.
- Feric M, Zhao B, Hoffert JD, Pisitkun T, Knepper MA. Large-scale phosphoproteomic analysis of membrane proteins in renal proximal and distal tubule. Am J Physiol Cell Physiol. 2011; 300: C755-70.
- 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.
- Zhao B, Knepper MA, Chou CL, Pisitkun T. Large-scale phosphotyrosine proteomic profiling of rat renal collecting duct epithelium reveals predominance of proteins involved in cell polarity determination. Am J Physiol Cell Physiol. 2012;302:C27-45
- Claxton JS, Sandoval PC, Liu G, Chou CL, Hoffert JD, Knepper MA. Endogenous carbamylation of renal medullary proteins. PLoS One. 2013 Dec 26;8(12):e82655.
- 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.
- Pickering CM, Grady C, Medvar B, Emamian M, Sandoval PC, Zhao Y, Yang CR, Jung HJ, Chou CL, Knepper MA. Proteomic profiling of nuclear fractions from native renal inner medullary collecting duct cells. Physiol Genomics. 2016; 48:154-66.
- 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. [Epub ahead of print] PMID: 27974320.
- 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.