Weining Lu, MD
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Title Associate Professor
Institution Boston University School of Medicine
Department Medicine
Division Nephrology
Address 650 Albany St
 Boston, MA 02118
Telephone (617) 414-1770
Email
Other Positions
Institution Boston Medical Center
Research Expertise & Professional Interests
The primary research interests in Dr. Lu’s laboratory focus on the genetics of renal tract development and congenital anomalies of the kidney and urinary tract (CAKUT). CAKUT is a complex birth defect with a diverse phenotypic spectrum, including kidney anomalies (e.g. aplastic, hypoplastic, dysplastic and cystic kidney, hydronephrosis), and ureteric anomalies (e.g. vesicoureteral reflux (VUR), reflux nephropathy, and obstructive uropathy). CAKUT is a genetically heterogeneous disorder with an incidence of 1 in 100 infants and accounts for up to 60% of the diagnoses underlying chronic kidney disease among the 0 to 12-year age group. CAKUT is also the leading causes of chronic kidney disease and renal failure in children and may manifest as primary renal diseases in adults as increasing numbers of children with congenital or inherited renal tract birth defects are surviving to adulthood. Despite the high incidence of CAKUT in children with chronic kidney disease, the genetic and molecular bases of CAKUT remain largely unclear.

Dr. Lu’s translational research program has adopted combined human and mouse molecular genetics approaches to identify a number of developmental genes to the study of renal tract development and CAKUT. The first human molecular genetics approach is to study individuals with CAKUT and apparent chromosomal defects, with the aim of using genomic imbalances and chromosomal rearrangements as signposts to identify these critical genes (reverse genetics). Thereafter, molecular identification and analysis of candidate genes as well as mutation studies in affected individuals with a familial pattern of CAKUT will be carried out (forward genetics). The second approach is to study temporal and spatial expression patterns of candidate genes in human and mouse. Meanwhile, knockout and transgenic mouse models of candidate genes will be studied to elucidate more fully their role in kidney and urinary tract development and disease. Once these candidate genes have been identified, a multidisciplinary approach will be taken to gain further mechanistic insights in vivo and in vitro on the role of these genes in normal and abnormal developmental processes of the kidney and urinary tract, and on the pathogenesis of CAKUT and chronic kidney disease. This multidisciplinary approach includes the application of human and mouse genetics, developmental biology, biochemistry, molecular biology, pharmacology, renal physiology and pathophysiology. The ultimate goal is to provide new knowledge of disease mechanisms underlying developmental antecedents of renal tract birth defect and chronic kidney disease, which will lead to innovative strategies for diagnosis and treatment. Current research activities in Dr. Lu’s lab include (1) Role of Slit-Robo signaling in kidney and urinary tract development, CAKUT, VUR, podocyte biology, and chronic kidney disease; (2) Identification of novel causative and susceptibility genes for renal tract birth defects in children with chronic kidney disease. Dr. Lu’s research program is supported by grants from the National Institute of Health (NIH), March of Dimes Foundation, and Centers for Therapeutic Innovation.
Self-described Keywords
  • CAKUT
  • Vesicoureteral reflux (VUR)
  • Podocyte biology
  • Kidney and urinary tract development
  • Lower urinary tract development and disease
  • Chronic kidney disease
  • Slit-Robo signaling pathway
Publications
1. Rasouly HM, Lu W. Lower urinary tract development and disease. Wiley Interdiscip Rev Syst Biol Med. 2013 Feb 13.
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2. Fan X, Li Q, Pisarek-Horowitz A, Rasouly HM, Wang X, Bonegio RG, Wang H, McLaughlin M, Mangos S, Kalluri R, Holzman LB, Drummond IA, Brown D, Salant DJ, Lu W. Inhibitory Effects of Robo2 on Nephrin: A Crosstalk between Positive and Negative Signals Regulating Podocyte Structure. Cell Rep. 2012 Jul 26; 2(1):52-61.
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3. Wang H, Li Q, Liu J, Mendelsohn C, Salant DJ, Lu W. Noninvasive assessment of antenatal hydronephrosis in mice reveals a critical role for robo2 in maintaining anti-reflux mechanism. PLoS One. 2011; 6(9):e24763.
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4. Paredes J, Sims-Lucas S, Wang H, Lu W, Coley B, Gittes GK, Bates CM. Assessing vesicoureteral reflux in live inbred mice via ultrasound with a microbubble contrast agent. Am J Physiol Renal Physiol. 2011 May; 300(5):F1262-5.
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5. Bonegio RG, Beck LH, Kahlon RK, Lu W, Salant DJ. The fate of Notch-deficient nephrogenic progenitor cells during metanephric kidney development. Kidney Int. 2011 May; 79(10):1099-112.
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6. Higgins AW, Alkuraya FS, Bosco AF, Brown KK, Bruns GA, Donovan DJ, Eisenman R, Fan Y, Farra CG, Ferguson HL, Gusella JF, Harris DJ, Herrick SR, Kelly C, Kim HG, Kishikawa S, Korf BR, Kulkarni S, Lally E, Leach NT, Lemyre E, Lewis J, Ligon AH, Lu W, Maas RL, MacDonald ME, Moore SD, Peters RE, Quade BJ, Quintero-Rivera F, Saadi I, Shen Y, Shendure J, Williamson RE, Morton CC. Characterization of apparently balanced chromosomal rearrangements from the developmental genome anatomy project. Am J Hum Genet. 2008 Mar; 82(3):712-22.
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7. Lu W, Quintero-Rivera F, Fan Y, Alkuraya FS, Donovan DJ, Xi Q, Turbe-Doan A, Li QG, Campbell CG, Shanske AL, Sherr EH, Ahmad A, Peters R, Rilliet B, Parvex P, Bassuk AG, Harris DJ, Ferguson H, Kelly C, Walsh CA, Gronostajski RM, Devriendt K, Higgins A, Ligon AH, Quade BJ, Morton CC, Gusella JF, Maas RL. NFIA haploinsufficiency is associated with a CNS malformation syndrome and urinary tract defects. PLoS Genet. 2007 May 25; 3(5):e80.
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8. Lu W, van Eerde AM, Fan X, Quintero-Rivera F, Kulkarni S, Ferguson H, Kim HG, Fan Y, Xi Q, Li QG, Sanlaville D, Andrews W, Sundaresan V, Bi W, Yan J, Giltay JC, Wijmenga C, de Jong TP, Feather SA, Woolf AS, Rao Y, Lupski JR, Eccles MR, Quade BJ, Gusella JF, Morton CC, Maas RL. Disruption of ROBO2 is associated with urinary tract anomalies and confers risk of vesicoureteral reflux. Am J Hum Genet. 2007 Apr; 80(4):616-32.
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9. Leach NT, Sun Y, Michaud S, Zheng Y, Ligon KL, Ligon AH, Sander T, Korf BR, Lu W, Harris DJ, Gusella JF, Maas RL, Quade BJ, Cole AJ, Kelz MB, Morton CC. Disruption of diacylglycerol kinase delta (DGKD) associated with seizures in humans and mice. Am J Hum Genet. 2007 Apr; 80(4):792-9.
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10. Wilson SJ, Amsler K, Hyink DP, Li X, Lu W, Zhou J, Burrow CR, Wilson PD. Inhibition of HER-2(neu/ErbB2) restores normal function and structure to polycystic kidney disease (PKD) epithelia. Biochim Biophys Acta. 2006 Jul; 1762(7):647-55.
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11. Hughes P, Robati M, Lu W, Zhou J, Strasser A, Bouillet P. Loss of PKD1 and loss of Bcl-2 elicit polycystic kidney disease through distinct mechanisms. Cell Death Differ. 2006 Jul; 13(7):1123-7.
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12. Cuajungco MP, Leyne M, Mull J, Gill SP, Lu W, Zagzag D, Axelrod FB, Maayan C, Gusella JF, Slaugenhaupt SA. Tissue-specific reduction in splicing efficiency of IKBKAP due to the major mutation associated with familial dysautonomia. Am J Hum Genet. 2003 Mar; 72(3):749-58.
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13. Nauli SM, Alenghat FJ, Luo Y, Williams E, Vassilev P, Li X, Elia AE, Lu W, Brown EM, Quinn SJ, Ingber DE, Zhou J. Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat Genet. 2003 Feb; 33(2):129-37.
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14. Liu S, Lu W, Obara T, Kuida S, Lehoczky J, Dewar K, Drummond IA, Beier DR. A defect in a novel Nek-family kinase causes cystic kidney disease in the mouse and in zebrafish. Development. 2002 Dec; 129(24):5839-46.
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15. Silverman ES, Le L, Baron RM, Hallock A, Hjoberg J, Shikanai T, Storm van's Gravesande K, Auron PE, Lu W. Cloning and functional analysis of the mouse 5-lipoxygenase promoter. Am J Respir Cell Mol Biol. 2002 Apr; 26(4):475-83.
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16. Lee ML, Lu W, Whitmore GA, Beier D. Models for microarray gene expression data. J Biopharm Stat. 2002 Feb; 12(1):1-19.
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17. Herron BJ, Lu W, Rao C, Liu S, Peters H, Bronson RT, Justice MJ, McDonald JD, Beier DR. Efficient generation and mapping of recessive developmental mutations using ENU mutagenesis. Nat Genet. 2002 Feb; 30(2):185-9.
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18. Lu W, Shen X, Pavlova A, Lakkis M, Ward CJ, Pritchard L, Harris PC, Genest DR, Perez-Atayde AR, Zhou J. Comparison of Pkd1-targeted mutants reveals that loss of polycystin-1 causes cystogenesis and bone defects. Hum Mol Genet. 2001 Oct 1; 10(21):2385-96.
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19. Mrug M, Green WJ, DasGupta S, Beier DR, Lu W, D'Eustachio P, Guay-Woodford LM. An integrated genetic and physical map of the 650-kb region containing the congenital polycystic kidney (cpk) locus on mouse chromosome 12. Cytogenet Cell Genet. 2001; 94(1-2):55-61.
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20. Pritchard L, Sloane-Stanley JA, Sharpe JA, Aspinwall R, Lu W, Buckle V, Strmecki L, Walker D, Ward CJ, Alpers CE, Zhou J, Wood WG, Harris PC. A human PKD1 transgene generates functional polycystin-1 in mice and is associated with a cystic phenotype. Hum Mol Genet. 2000 Nov 1; 9(18):2617-27.
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21. Lu W, Lu W. Chinese herbs and urothelial carcinoma. N Engl J Med. 2000 Oct 26; 343(17):1269; author reply 1269-70.
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22. Lu W, Fan X, Basora N, Babakhanlou H, Law T, Rifai N, Harris PC, Perez-Atayde AR, Rennke HG, Zhou J. Late onset of renal and hepatic cysts in Pkd1-targeted heterozygotes. Nat Genet. 1999 Feb; 21(2):160-1.
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23. Lu W, Peissel B, Babakhanlou H, Pavlova A, Geng L, Fan X, Larson C, Brent G, Zhou J. Perinatal lethality with kidney and pancreas defects in mice with a targetted Pkd1 mutation. Nat Genet. 1997 Oct; 17(2):179-81.
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24. Geng L, Segal Y, Pavlova A, Barros EJ, Löhning C, Lu W, Nigam SK, Frischauf AM, Reeders ST, Zhou J. Distribution and developmentally regulated expression of murine polycystin. Am J Physiol. 1997 Apr; 272(4 Pt 2):F451-9.
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Co-Authors  
Beck, Laurence
Bonegio, Ramon
Fan, Xueping
Salant, David
See all (4) people