Weining Lu, MD
Associate Professor
Boston University School of Medicine
Dept of Medicine
Nephrology Section

MD, Zhejiang University
MSc, Northeastern University



The primary research interests in Dr. Lu’s laboratory focus on three scientific areas: 1. Molecular genetics of renal tract development and birth defects in the kidney and urinary tract; 2. Biological functions and disease mechanisms of the renal tract birth defect genes and their roles after birth in common kidney disease; 3. SLIT-ROBO and ZEB signaling in kidney development and disease.

Congenital anomalies of the kidney and urinary tract (CAKUT) is a complex birth defect with a diverse phenotypic spectrum, including kidney anomalies (e.g. renal agenesis, multicystic dysplastic kidney (MCDK), renal cystic disease, hydronephrosis), and ureteric anomalies (e.g. vesicoureteral reflux (VUR), reflux nephropathy, and obstructive uropathy) (Ref 1, 2). CAKUT is a genetically heterogeneous disorder with an incidence of 1 in 100 infants and accounts for up to 50-60% of the diagnoses underlying chronic kidney disease among the 0 to 12-year age group. CAKUT is also the leading cause 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 kidney and urinary tract development and pathogenesis of CAKUT and chronic kidney disease. The first human molecular genetics approach is to study individuals with CAKUT and apparent genetic defects, with the aim of using gene mutations, genomic imbalances and chromosomal rearrangements as signposts to identify these critical genes (reverse genetics) (Ref 2). 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) (Ref 2, 3). 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 roles in kidney and urinary tract development and disease (Ref 4-6). Once these candidate genes (e.g. SLIT2, ROBO2, ZEB2) 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 (Ref 4-6). This multidisciplinary approach includes the application of human and mouse genetics, developmental biology, protein biochemistry, molecular biology, pathology, pharmacology, and novel therapeutics. The goal is to provide new knowledge of disease mechanisms underlying developmental antecedents of kidney and urinary tract disorders, which will lead to discoveries of novel drug targets and therapeutics for patients with common kidney diseases (Ref 6).

Current research activities in Dr. Lu’s lab include (1) Role of SLIT2-ROBO2 and ZEB2 signaling in renal tract development and disease, podocyte biology and injury, pericyte biology and renal fibrosis; (2) Discovery of novel causative and susceptibility genes (e.g. ROBO2, ZEB2) for renal tract birth defects in children with chronic kidney disease; (3) Identify novel drug targets and therapeutics for patients with chronic kidney disease. Dr. Lu’s research program is supported by grants from the National Institutes of Health (NIH), March of Dimes Foundation, Pfizer Centers for Therapeutic Innovation, and Massachusetts Life Sciences Center.

References:

(1). Lu W, Bush KT, Nigam SK. Regulation of ureteric bud outgrowth and the consequences of disrupted development. In Kidney Development, Disease, Repair and Regeneration (ed. Little MH), Pages 209-227 (Elsevier, 2016) (http://www.sciencedirect.com/science/article/pii/B9780128001028000187)
(2). Lu W, van Eerde AM, Fan X, et al. Disruption of ROBO2 is associated with urinary tract anomalies and confers risk of vesicoureteral reflux. Am J Hum Genet 2007; 80:616-632. PMID: 17357069 (http://www.ncbi.nlm.nih.gov/pubmed/17357069).
(3) Hwang DY, Kohl S, Fan X, et al. Mutations of the SLIT2-ROBO2 pathway genes SLIT2 and SRGAP1 Confer Risk for Congenital Anomalies of the Kidney and Urinary Tract. Hum Genet 2015; 134(8):905-916; PMID: 26026792 (http://www.ncbi.nlm.nih.gov/pubmed/26026792).
(4). Fan X, Li Q, Pisarek-Horowitz A, et al. Inhibitory effects of Robo2 on nephrin: a crosstalk between positive and negative signals regulating podocyte structure. Cell Reports 2012; 2:52-61. PMID: 22840396 (http://www.ncbi.nlm.nih.gov/pubmed/22840396).
(5). Rasouly HM, Kumar S, Chen S, et al. Loss of Zeb2 in mesenchyme-derived nephrons causes primary glomerulocystic kidney disease. Kidney Int 2016; Aug 30. PMID: 27591083 (http://www.ncbi.nlm.nih.gov/pubmed/27591083).
(6) Fan X, Yang H, Kumar S, et al. SLIT2/ROBO2 signaling pathway inhibits nonmuscle myosin IIA activity and destabilizes kidney podocyte adhesion. JCI Insight 2016, Nov 17; 1(19):e86934. PMID: 27882344 (https://www.ncbi.nlm.nih.gov/pubmed/27882344)

CURRENT LAB MEMBERS:

Xueping Fan (PhD, McGill University), Instructor in Medicine, 617-414-1772, xpfan@bu.edu.

Sudhir Kumar (DVM, Ludwig Maximilians University Munich), Postdoc, 617-638-7353, kumars@bu.edu.

Richa Sharma (PhD, SGPGIMS Medical Institute in Lucknow), Postdoc, 617-414-2298, richa26@bu.edu.

Tou S. Thao (MS in Medical Sciences Program, Graduate Medical Sciences, Boston University School of Medicine), Graduate student, 617-414-2238, tthao@bu.edu

PHD STUDENTS GRADUATED RECENTLY:

Anna Pisarek-Horowitz (PhD, Graduate Program in Molecular Translational Medicine, Graduate Medical Sciences, Boston University School of Medicine).

Hila Milo Rasouly (PhD, Graduate Program in Genetics and Genomics, Graduate Medical Sciences, Boston University School of Medicine).

Inquiry about thesis project and research position in Dr. Lu’s lab, please contact: wlu@bu.edu

Boston Medical Center


Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.

  1. Gore BB, Miller SM, Jo YS, Baird MA, Hoon M, Sanford CA, Hunker A, Lu W, Wong RO, Zweifel LS. Roundabout receptor 2 maintains inhibitory control of the adult midbrain. Elife. 2017 Apr 10; 6. PMID: 28394253; DOI: 10.7554/eLife.23858;.
  2. Vivante A, Mann N, Yonath H, Weiss AC, Getwan M, Kaminski MM, Bohnenpoll T, Teyssier C, Chen J, Shril S, van der Ven AT, Ityel H, Schmidt JM, Widmeier E, Bauer SB, Sanna-Cherchi S, Gharavi AG, Lu W, Magen D, Shukrun R, Lifton RP, Tasic V, Stanescu HC, Cavaillès V, Kleta R, Anikster Y, Dekel B, Kispert A, Lienkamp SS, Hildebrandt F. A Dominant Mutation in Nuclear Receptor Interacting Protein 1 Causes Urinary Tract Malformations via Dysregulation of Retinoic Acid Signaling. J Am Soc Nephrol. 2017 Aug; 28(8):2364-2376. PMID: 28381549; DOI: 10.1681/ASN.2016060694;.
  3. Chen J, Van Der Ven A, Newman J, Vivante A, Mann N, Shril S, Schulz J, Ityel H, Schmidt MJ, Widmeier E, Gileadi O, Sharrocks A, Palmer K, Costantini K, Cebrian C, Thowfeequ S, Wenger RH, Bauer SB, Lee RS, Lu W, Lienkamp SS, Lifton RP, Tasic V, Kehinde EO, Hildebrandt F. ETV4 mutation in a patient with congenital anomalies of the kidney and urinary tract. International Journal of Pediatrics and Child Health. 2016; 2(4):61-71. View Publication
  4. Fan X, Yang H, Kumar S, Tumelty KE, Pisarek-Horowitz A, Rasouly HM, Sharma R, Chan S, Tyminski E, Shamashkin M, Belghasem M, Henderson JM, Coyle AJ, Salant DJ, Berasi SP, Lu W. SLIT2/ROBO2 signaling pathway inhibits nonmuscle myosin IIA activity and destabilizes kidney podocyte adhesion. JCI Insight. 2016 Nov 17; 1(19):e86934.View Related Profiles. PMID: 27882344.
  5. Havasi A, Lu W, Cohen HT, Beck L, Wang Z, Igwebuike C, Borkan SC. Blocking peptides and molecular mimicry as treatment for kidney disease. Am J Physiol Renal Physiol. 2017 Jun 01; 312(6):F1016-F1025.View Related Profiles. PMID: 27654896; DOI: 10.1152/ajprenal.00601.2015;.
  6. Rasouly HM, Kumar S, Chan S, Pisarek-Horowitz A, Sharma R, Xi QJ, Nishizaki Y, Higashi Y, Salant DJ, Maas RL, Lu W. Loss of Zeb2 in mesenchyme-derived nephrons causes primary glomerulocystic disease. Kidney Int. 2016 Dec; 90(6):1262-1273.View Related Profiles. PMID: 27591083; DOI: 10.1016/j.kint.2016.06.037;.
  7. Lu W, Bush KT, Nigam SK. Regulation of Ureteric Bud Outgrowth and the Consequences of Disrupted Development. In "Kidney Development, Disease, Repair and Regeneration" (ed. Little MH). Academic Press. Elsevier. 2016; 209-227. View Publication
  8. Zhang Y, Fan J, Ho JW, Hu T, Kneeland SC, Fan X, Xi Q, Sellarole MA, de Vries WN, Lu W, Lachke SA, Lang RA, John SW, Maas RL. Crim1 regulates integrin signaling in murine lens development. Development. 2016 Jan 15; 143(2):356-66. PMID: 26681494; PMCID: PMC4725338; DOI: 10.1242/dev.125591;.
  9. Vivante A, Kleppa MJ, Schulz J, Kohl S, Sharma A, Chen J, Shril S, Hwang DY, Weiss AC, Kaminski MM, Shukrun R, Kemper MJ, Lehnhardt A, Beetz R, Sanna-Cherchi S, Verbitsky M, Gharavi AG, Stuart HM, Feather SA, Goodship JA, Goodship TH, Woolf AS, Westra SJ, Doody DP, Bauer SB, Lee RS, Adam RM, Lu W, Reutter HM, Kehinde EO, Mancini EJ, Lifton RP, Tasic V, Lienkamp SS, Jüppner H, Kispert A, Hildebrandt F. Mutations in TBX18 Cause Dominant Urinary Tract Malformations via Transcriptional Dysregulation of Ureter Development. Am J Hum Genet. 2015 Aug 6; 97(2):291-301. PMID: 26235987; DOI: 10.1016/j.ajhg.2015.07.001;.
  10. Hwang DY, Kohl S, Fan X, Vivante A, Chan S, Dworschak GC, Schulz J, van Eerde AM, Hilger AC, Gee HY, Pennimpede T, Herrmann BG, van de Hoek G, Renkema KY, Schell C, Huber TB, Reutter HM, Soliman NA, Stajic N, Bogdanovic R, Kehinde EO, Lifton RP, Tasic V, Lu W, Hildebrandt F. Mutations of the SLIT2-ROBO2 pathway genes SLIT2 and SRGAP1 confer risk for congenital anomalies of the kidney and urinary tract. Hum Genet. 2015 Aug; 134(8):905-16.View Related Profiles. PMID: 26026792; PMCID: PMC4497857; DOI: 10.1007/s00439-015-1570-5;.
Showing 10 of 35 results. Show More

This graph shows the total number of publications by year, by first, middle/unknown, or last author.

Bar chart showing 35 publications over 16 distinct years, with a maximum of 5 publications in 2016

YearPublications
19972
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20081
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20172

Dr. Lu has completed the Boston University Medical Center CTSI Mentor Training Program.

Available to Mentor as: (Review Mentor Role Definitions):
  • Advisor
  • Career Mentor
  • Co-Mentor or Peer Mentor
  • Diversity Mentor
  • Education Mentor
  • Project Mentor
  • Research / Scholarly Mentor
  • Work / Life Integration Mentor
Contact for Mentoring:
  • Email (see 'Contact Info')

650 Albany St Evans Biomed Research Ctr
Boston MA 02118
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