I have a Ph.D. in molecular and cellular biology and biochemistry. I have a broad background in renal physiology, pathology and renal medicine from my combined research and clinical nephrology fellowship training at MGH/BWH. I have 14 years of experience working in the basic science fields of epithelial cell biology and protein/vesicle trafficking. I have also been practicing clinical nephrology for 14 years.
I have a Ph.D. in molecular and cellular biology and biochemistry. I have a broad background in renal physiology, pathology and renal medicine from my combined research and clinical nephrology fellowship training at MGH/BWH. I have 14 years of experience working in the basic science fields of epithelial cell biology and protein/vesicle trafficking. I have also been practicing clinical nephrology for 14 years. The focus of my laboratory is the study of epithelial biology, with an emphasis on membrane protein and vesicle trafficking, in both tubular cells, and more recently in podocytes as well. We have established multiple in vitro and in vivo model systems to study the pathophysiology of kidney diseases, and applied a variety of advanced imaging technologies, in combination with complex biochemical and molecular biological methods, to interrogate epithelial cell function. We have received research support from the NIH/NIDDK (RO1, R21, R03, and research supplemental grant), American Society of Nephrology, Nephcure Foundation, S&R Foundation (Ryuji Ueno Award), and MGH/Harvard Medical School. I am dedicated to investigating the basic physiology and pathological process of kidney dysfunction, and seeking novel therapeutic interventions for treating kidney diseases.
Positions and Honors
1997-2000 Research fellow, Dept. Medicine, BIDMC, Harvard Medical School.
2000-2001 Internship, Internal Medicine, New York University Medical Center.
2001-2002 Residency, Internal Medicine, New York University Medical Center.
2002-2006 Fellowship in Nephrology, MGH/BWH, Harvard Medical School.
2006-2011 Instructor in Medicine, Harvard Medical School
Clinical Assistant in Medicine, Division of Nephrology/MGH
2012- present Assistant professor in Medicine, Harvard Medical School
HONORS AND AWARDS
2006-2011 Mentored Clinical Research Award (KO8 award), NIH/NIDDK
2009-2012 Gottschalk Research Grant, American Society of Nephrology (ASN)
2009-1012 Claflin Distinguished Scholars, MGH/ECOR
2009-2012 NIH/NIDDK RO3
2012-2014 Milton Award, Harvard Medical School
2012-2014 NIH/NIDDK R21
2012-2015 Nephcure foundation research grant
2013-2018 NIH/NIDDK R01
2015 Recipient of the S&R Foundation Ryuji Ueno Award, APS
1997-present Member, American Society of Nephrology (ASN)
2000-present Member, American College of Physician-American Society of Internal Medicine
2007-present Member, American Society for Biochemistry and Molecular Biology (ASBMB)
2007-present Member, National Kidney Foundation (NKF)
2008-2010 Member, Basic Science Committee at American Society of Nephrology (ASN)
2010-present Committee member, scientific advisory group, cell biology and physiology (ASN)
2009-present Faculty Member of Faculty 1000 (F1000).
2010-present Member, the American Physiological Society (APS)
2012-present Member, the American Heart Association (AHA)
Selected Peer-reviewed Publications
1. Lu HA, Tian-Xiao Sun, Richard B, Blackburn K, McLaughlin M, and Dennis Brown. Inhibition of
endocytosis causes phosphorylation (S256)-independent plasma membrane accumulation of AQP2. A
J Renal Physiol 286:F233-F243. 2004. PMID: 14519593
2. Lu HA, Sun TX, Matsuzaki T, Yi XH, Eswara J, Bouley R, McKee M, Brown D. Heat shock protein 70 interacts with aquaporin-2 (AQP2) and regulates its trafficking. J.Biol.Chem., 2007, Sep 28;282(39):28721-28732. PMID: 17636261
3. Yi X; Bouley R, Lin HY, Bechoua S, Sun TX; Del Re E, Shioda T, Raychowdhury MK, Lu HA; Abou-Samara AB, Brown D, Ausiello DA. Alix (AIP1) is a Vasopressin Receptor (V2R) interacting protein that Increases Lysosomal Degradation of the V2R. Am J Physiol Renal Physiol., 2007, May;292(5):F1303-13. PMID: 17287200
4. Paunescu TG, Da Silva N, Russo LM, McKee M, Lu HA, Breton S, Brown D. Association of soluble adenylyl cyclase with the V-ATPase in renal epithelial cells. Am J Physiol Renal Physiol. 2008 Jan; 294(1):F130-8. PMID: 17959750
5. Bouley R, Udo H, Lu HA, Nunes P, Brown D. Bypassing vasopressin receptor signaling pathways in nephrogenic diabetes insipidus. Semin Nephrol. 2008 May;28(3):266-78. PMID: 18519087
6. Lu HA, Matsuzaki T, Bouley R, Hasler U, Qin QH, Brown D. The phosphorylation state of serine 256 is dominant over that of serine 261 in the regulation of AQP2 trafficking in renal epithelial cells. Am J Physiol Renal Physiol. 2008 Jul;295(1):F290-4. PMID: 18434387
7. Brown D, Nunes P, Hasler U, Bouley R, Lu HA. Phosphorylation events and the modulation of aquaporin 2 cell surface expression. Curr Opin Nephrol Hypertension. 2008 Sep;17(5):491-8. PMID: 18695390
8. Hasler U, Nunes P, Bouley R, Lu HA, Matsuzaki T, Brown D. Acute Hypertonicity Alters Aquaporin-2 Trafficking and Induces a MAPK-dependent Accumulation at the Plasma Membrane of Renal Epithelial Cells. J. Biol.Chem., 2008 Sep 26;283(39):26643-61. PMID:18664568.
9. Nunes P, Hasler U, McKee M, Lu HA, Bouley R, Brown D, A fluorimetry-based ssYFP secretion assay to monitor vasopressin-induced exocytosis in LLC-PK1 cells expressing aquaporin-2 (AQP2). Am J Physiol Cell Physiol. 2008 Dec;295(6):C1476-87. PMID: 18799651
10. Bouley R, Palomino Z, Tang SS, Nunes P, Kobori H, Lu HA, Shum WW, Sabolic I, Brown D, Ingelfinger JR, Jung FF. Angiotensin II and hypertonicity modulate proximal tubular aquaporin 1 expression. Am J Physiol Renal Physiol. 2009 Dec;297(6):F1575-86. PMID: 19776169
11. Bouley R, Lu HA, Nunes P, Da Silva N, McLaughlin M, Chen Y, Brown D. Calcitonin has a vasopressin
like effect on aquaporin-2 trafficking and urinary concentration. J Am Soc Nephrol. 2011 Jan;22(1):59-72.
12. Li W, Zhang Y, Bouley R, Chen Y, Matsuzaki T, Nunes P, Hasler U, Brown D, Lu HA. Simvastatin enhances aquaporin 2 surface expression and urinary concentration in vasopressin deficient Brattleboro rats through modulation of Rho GTPase. Am J Physiol Renal Physiol, 2011 Aug 301(2): F309-318. PMID: 21511701
Hightlighted by Editorial: Statins affect AQP2 traffic. Wade J.B. Am J Physiol Renal Physiol. 2011 Aug 301: F308
13. Yui N, Lu HA, Bouley R, Brown D. AQP2 is Necessary for Vasopressin and Forskolin Mediated Filamentous Actin Depolymerization in Renal Epithelial Cells. Biol Open. 2012 Feb 15;1(2):101-8. PMID:
14. Rice W L, Zhang Y, Chen Y, Matsuzaki T, Brown D, Lu HA. Differential, phosphorylation dependent trafficking of AQP2 in LLC-PK1 cells. PLoS One, 2012;7(2):e32843. PMID: 22403603.
15. Brown D, Bouley R, Paunescu T, Breton S, Lu A. New insights into the dynamic regulation of water and acid/base balance by renal epithelial cells. Am J Physiol Renal Physiol. 2012 May;302(10):C1421-33. Review. PMID: 22460710.
16. Chen Y, Rice W, Gu Z Z, Li J, Huang JJ, Brenner M, Van Hok A, Xiong JP, Gundersen G, Norman J, Hsu V, Fenton, R, Brown D, Lu HA. Role of Aquaporin 2 in promoting cell migration and epithelial morphogenesis. J Am Soc Nephrol. 2012 Sep;23(9):1506-17. PMID: 22859853
Highlighted by Editorial: Aquaporin 2: not just for moving water. Jeff M. Sands. J Am Soc Nephrol. 2012 Sept;23(9)
Figure 6 was used for the journal cover image for J Am Soc Nephrol. Issue 2012 Sept;23(9)
17. Yui N, Lu HA, Chen Y, Bouley R, Brown D. Basolateral targeting and microtubule dependent transcytosis of the aquaporin-2 water channel. Am J Physiol Cell Physiol. 2013 Jan 1;304(1):C38-48.:23015545.
18. Huang J, McKee M, Huang HD, Xiang A, Davidson AJ, Lu HA. A Zebrafish model of conditional targeted podocytes ablation and regeneration. Kidney Int. 2013 Mar 6. PMID 23466998.
19. Brown D and Lu HA. AQP2 inhibitors: fishing in the chemical pool. Editorial. J Am Soc Nephrol. April 2013
20. Păunescu TG, Lu HA, Russo LM, Pastor-Soler NM, McKee M, McLaughlin MM, Bartlett BE, Breton S, Brown D. Vasopressin induces apical expression of caveolin in rat kidney collecting duct principal cells. Am J Physiol Renal Physiol. 2013 Dec 15;305(12):F1783-95. PMID: 24133120
21. Nomura N, Nunes P, Bouley R, Nair AV, Shaw S, Ueda E, Pathomthongtaweechai N, Lu HA, Brown D. High throughput chemical screening identifies AG-490 as a stimulator of aquaporin 2 membrane expression and urine concentration. Am J Physiol Cell Physiol. 2014 Jun 18. PMID: 24944200
22. Arthur J, Huang J, Nomura N, Jin WW, Li W, Brown D, Lu HA. Characterization of the putative phosphorylation sites of the AQP2 c-terminus and their role in AQP2 trafficking in LLC-PK1 cells. Am J Physiol Renal Physiol. 2015, Oct 15;309(8):F673-9. PMID: 26290367
23. Rice W, Li W, Mamuya F, McKee M, Paunescu, Lu HA. Polarized trafficking of AQP2 revealed in three-dimensional epithelial culture. PLoS One. 2015 Jul 6;10(7). PMID: 26147297.
24. Cheung PW, Nomura N, Nair AV, Pathomthongtaweechai N, Ueberdiek L, Lu HA, Brown D, Bouley R. EGF Receptor Inhibition by Erlotinib Increases Aquaporin 2-Mediated Renal Water Reabsorption.. J Am Soc Nephrol. 2016 Mar 9. PMID: 26961350
Complete List of Published Work in MyBibliography: http://www.ncbi.nlm.nih.gov/myncbi/collections/bibliography/41158049/