Weining Lu MD

Associate Professor, Nephrology

650 Albany St | (617) 414-1770
Weining Lu
Sections

Nephrology

Centers

Evans Center for Interdisciplinary Biomedical Research

Biography

Dr. Lu is a Principal Investigator and Associate Professor of Medicine, Pathology, and Laboratory Medicine at Boston University. He also acts as a Primary Mentor for medical students, graduate students, fellows, and postdocs in the Nephrology Section of the Department of Medicine. Dr. Lu has a long-standing interest in nephrology and genetics, including kidney development, congenital anomalies of the kidney and urinary tract (CAKUT), vesicoureteral reflux (VUR), podocyte biology and injury, ROBO/SLIT signaling, and chronic kidney disease. His significant scientific contributions in the field include: (1) the discovery of ROBO2 as one of the causative genes for CAKUT and VUR (OMIM 610878), (2) the identification of SLIT2/ROBO2 signaling as a novel drug target for proteinuric kidney diseases, which negatively regulates nephrin signaling, non-muscle myosin IIA signaling and podocyte adhesions in podocyte biology and injury, (3) the creation of the first animal model for autosomal dominant polycystic kidney disease (PKD1), and (4) the discovery of ZEB2 as one of the causative genes for glomerulocystic kidney disease and its essential role in kidney stromal progenitor cell differentiation and renal fibrosis. In recognition of his seminal contribution to the development of a potential new drug for chronic kidney disease in collaboration with Pfizer, Dr. Lu was named the 2019 Boston University Innovator of the Year, an award bestowed annually on a faculty member who “translates his/her world-class research into inventions and innovations that benefit humankind” (https://www.bu.edu/articles/2019/weining-lu-kidney-researcher-innovator-of-the-year/).

RESEARCH PROGRAM:

The primary research interests of Dr. Lu’s laboratory are focused on four scientific areas. 1) Molecular genetics of the kidney and urinary tract development and congenital anomalies of the kidney and urinary tract (CAKUT). 2) Biological function and disease mechanism of kidney and urinary tract birth defect genes and their roles after birth in chronic kidney diseases. 3) SLIT/ROBO and ZEB signaling in kidney and urinary tract development and disease. 4) Discovery and development of novel drug targets and therapeutics for patients with chronic kidney diseases.

Congenital anomalies of the kidney and urinary tract (CAKUT) is a complex congenital disability with a diverse phenotypic spectrum, including kidney anomalies (e.g., renal agenesis, multicystic dysplastic kidney, hydronephrosis), and ureteric anomalies (e.g., vesicoureteral reflux, 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 childhood diagnoses underlying chronic kidney disease. CAKUT is also the leading cause and a significant risk factor for kidney failure in children and young adults under 40 (Ref 3).

Dr. Lu’s translational research program has adopted combined human and mouse molecular genetics approaches to identify several developmental genes that are important in kidney and urinary tract development and pathogenesis of CAKUT. The first human molecular genetics approach is to study individuals with CAKUT and apparent genetic defects and to use gene mutations, genomic imbalances, and chromosomal rearrangements as signposts to identify disease-causal genes (reverse genetics) (Ref 2). After that, molecular identification and analysis of disease genes and mutation studies in affected individuals with a familial pattern of CAKUT will be carried out (forward genetics) (Ref 2, 4). The second approach is to study temporal and spatial expression patterns of disease genes in human and mouse models. Concurrently, the phenotype of knockout and transgenic mouse models will be examined to more fully elucidate the roles of disease genes in kidney and urinary tract development and disease. Once these disease genes (e.g., ROBO2, SLIT2, ZEB2) are identified, a multidisciplinary research 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 kidney injury after birth (Ref 5-8). This multidisciplinary approach includes biomedical research techniques in molecular genetics, developmental biology, protein biochemistry, molecular biology, pathology, pharmacology, pre-clinical animal models, patient samples, and biomarker studies. The goal of this research program is to provide new knowledge of the biological mechanism that leads to CAKUT and kidney injury after birth, which has already led to the discovery of novel drug targets and therapeutics for patients with chronic kidney disease (Ref 7-9) (https://www.eurekalert.org/pub_releases/2016-11/bumc-rip_1111516.php & https://www.eurekalert.org/pub_releases/2020-05/buso-rsn050420.php).

Current research projects in Dr. Lu’s lab include (1) the development of novel therapeutics for patients with proteinuric kidney diseases, (2) molecular mechanisms of SLIT/ROBO and ZEB signaling in podocyte biology/injury and renal fibrosis, and (3) pathogenesis of VUR and CAKUT and identification of novel causative birth defect genes for CAKUT/VUR in patients. Dr. Lu’s research program is supported by grants from the National Institutes of Health (NIH) and Pfizer’s Centers for Therapeutic Innovation (CTI).

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) Calderon-Margalit R, Golan E, Twig G, et al. History of Childhood Kidney Disease and Risk of Adult End-Stage Renal Disease. N Engl J Med 2018; 378(5):4280438. PMID: 29385364 (https://www.ncbi.nlm.nih.gov/pubmed/29385364).
(4) 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).
(5). 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).
(6). 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).
(7) 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).
(8) Pisarek-Horowitz A, Fan X, Kumar S, et al. Loss of Roundabout Guidance Receptor 2 (Robo2) in Podocytes Protects Adult Mice from Glomerular Injury by Maintaining Podocyte Foot Process Structure. American Journal of Pathology, 2020; 190(4):799-816. PMID: 32220420.
(https://ajp.amjpathol.org/article/S0002-9440(20)30024-9/pdf).
(9) Beck LH, Berasi SP, J. Copley B, Gorman D, Levy DI, Lim CN, Henderson JM, Salant DJ, Lu W. PODO: Trial Design: Phase 2 Study of PF-06730512 in Focal Segmental Glomerulosclerosis. Kidney Int Rep 2021; 6(6):1629-1633. PMID: 34169203. DOI: https://doi.org/10.1016/j.ekir.2021.03.892


VISION STATEMENT of Dr. Lu’s laboratory on science and medical education: (1) to advance new knowledge, biomedical innovation, and scientific learning; (2) to promote understanding, collaboration, diversity, and inclusion in biomedical research and education; (3) to contribute positively to the scientific, medical and biomedical community, and society at large.
CORE VALUES: Curiosity, Innovation, Diversity, Equity, Inclusion, Hard work, Perseverance, Honesty, Fair play, Courage, Integrity.

CURRENT LAB MEMBERS:

Xueping Fan (PhD, McGill University), Research Scientist and Assistant Professor, 617-414-1772, xpfan@bu.edu.

Sudhir Kumar (DVM, PhD, Ludwig Maximilians University Munich), Research Scientist and Assistant Professor, 617-638-7353, kumars@bu.edu.

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

Aneesha Pydi (Boston University 7 Year Combined Liberal Arts / Medical Education Program), MD medical student, aneeshap@bu.edu

Rhianna DelBene (Chemistry Major, Boston University College of Arts and Sciences), Undergraduate student, BU Undergraduate Research Opportunities Program (UROP), rdelbene@bu.edu

Emily Zaltz (Health Science Major, Boston University Sargent College of Health and Rehabilitation Sciences), Undergraduate pre-medical student, BU Undergraduate Research Opportunities Program (UROP),

Jessica Siu (Biology Major, Boston University College of Arts & Sciences), Undergraduate pre-dental student, BU Undergraduate Research Opportunities Program (UROP), jksiu88@bu.edu

Aksel Laudon (Biomedical Engineering Major, Boston University College of Engineering), BS/MD student, Modular Medical/Dental Integrated Curriculum (MMEDIC) early acceptance program to BUSM MD program, BU Undergraduate Research Opportunities Program (UROP), alaudon@bu.edu


PHD STUDENTS GRADUATED RECENTLY:

Hila Milo Rasouly (PhD, Graduate Program in Genetics and Genomics, Graduate Medical Sciences, Chobanian and Avedisian School of Medicine). PhD thesis title: “Discovery and analysis of genes important in kidney development and disease.”

Anna Pisarek-Horowitz (PhD, Graduate Program in Molecular Translational Medicine, Graduate Medical Sciences, Chobanian and Avedisian School of Medicine). PhD thesis title: “Functional characterization of the SLIT2-ROBO2 signaling pathway in the podocyte”.

MS STUDENTS GRADUATED RECENTLY:

Tou S. Thao (MS in Medical Sciences Program, Graduate Medical Sciences, Chobanian and Avedisian School of Medicine). MS thesis title: “Functional study of ROBO2 missense mutation identified in patients with congenital anomalies of the kidney and urinary tract (CAKUT)”.

Biomedical research projects for students and postdocs are available. For inquiries regarding these research opportunities, please contact Dr. Lu at wlu@bu.edu

Other Positions

Education

Medicine, MD, Zhejiang University, 1989

Biomedical Sciences, MSc, Northeastern University, 1996

Publications

Published on 11/29/2022

Kumar S, Fan X, Milo Rasouly H, Sharma R, Salant DJ, Lu W. ZEB2 controls kidney stromal progenitor differentiation and inhibits abnormal myofibroblast expansion and kidney fibrosis. JCI Insight. 2022 Nov 29. PMID: 36445780.

Published on 9/1/2022

Wu CW, Lim TY, Wang C, Seltzsam S, Zheng B, Schierbaum L, Schneider S, Mann N, Connaughton DM, Nakayama M, van der Ven AT, Dai R, Kolvenbach CM, Kause F, Ottlewski I, Stajic N, Soliman NA, Kari JA, El Desoky S, Fathy HM, Milosevic D, Turudic D, Al Saffar M, Awad HS, Eid LA, Ramanathan A, Senguttuvan P, Mane SM, Lee RS, Bauer SB, Lu W, Hilger AC, Tasic V, Shril S, Sanna-Cherchi S, Hildebrandt F. Copy Number Variation Analysis Facilitates Identification of Genetic Causation in Patients with Congenital Anomalies of the Kidney and Urinary Tract. Eur Urol Open Sci. 2022 Oct; 44:106-112. PMID: 36185583.

Published on 4/12/2022

Liron David, Laurel Martinez, Qiongchao Xi, Xueping Fan, Kameron A. Kooshesh, Ying Zhang, Jagesh V. Shah, Weining Lu, Richard L. Maas, Hao Wu. Piezo mechanosensory channels regulate centrosome integrity. bioRxiv, Cold Spring Harbor Laboratory. 2022.

Published on 4/3/2021

Beck LH, Berasi SP, Copley JB, Gorman D, Levy DI, Lim CN, Henderson JM, Salant DJ, Lu W. PODO: Trial Design: Phase 2 Study of PF-06730512 in Focal Segmental Glomerulosclerosis. Kidney Int Rep. 2021 Jun; 6(6):1629-1633. PMID: 34169203.

Published on 2/2/2021

Stephen Berasi, Janet Elizabeth Buhlmann, Nathan Higginson-Scott, Michael Shamashkin, Matthew Russo, Stefano V. Gulla, Zong Sean Juo, Sreekumar R. Kodangattil, Weining Lu, Xueping Fan, David J. Salant. RECOMBINANT ROBO2 PROTEINS, COMPOSITIONS, METHODS AND USES THEREOF. 2021.

Published on 10/23/2020

Berasi S, Buhlmann J, Shamashkin M, Russo M, Yang Y, Knowlton K, Higginson-Scott N, Lin H, Andresen C, Jones R, Fan X, Kumar S, Sharma R, Pydi A, Salant DJ, and Lu W. A ROBO2 fusion protein (PF-06730512) traps SLIT ligands and therapeutically ameliorates podocyte injury. 2020 Kidney Week. 2020.

Published on 10/16/2020

Sarah R Vargas, Casey Ritenour, Cheryl Tyszkiewicz, Seo-Kyoung Hwang, Chang-Ning Liu, Lindsay Tomlinson, Stephen Berasi, Xueping Fan, Weining Lu, Hongying Yang. Deep Learning for Quantitative Image Analysis of Morphological Changes in Podocyte Foot Processes in Electron Micrographs of Rat Model of Passive Heymann Nephritis. 2020 Digital Pathology & AI Congress. 2020.

Published on 9/4/2020

Connaughton DM, Dai R, Owen DJ, Marquez J, Mann N, Graham-Paquin AL, Nakayama M, Coyaud E, Laurent EMN, St-Germain JR, Blok LS, Vino A, Klämbt V, Deutsch K, Wu CW, Kolvenbach CM, Kause F, Ottlewski I, Schneider R, Kitzler TM, Majmundar AJ, Buerger F, Onuchic-Whitford AC, Youying M, Kolb A, Salmanullah D, Chen E, van der Ven AT, Rao J, Ityel H, Seltzsam S, Rieke JM, Chen J, Vivante A, Hwang DY, Kohl S, Dworschak GC, Hermle T, Alders M, Bartolomaeus T, Bauer SB, Baum MA, Brilstra EH, Challman TD, Zyskind J, Costin CE, Dipple KM, Duijkers FA, Ferguson M, Fitzpatrick DR, Fick R, Glass IA, Hulick PJ, Kline AD, Krey I, Kumar S, Lu W, Marco EJ, Wentzensen IM, Mefford HC, Platzer K, Povolotskaya IS, Savatt JM, Shcherbakova NV, Senguttuvan P, Squire AE, Stein DR, Thiffault I, Voinova VY, Somers MJG, Ferguson MA, Traum AZ, Daouk GH, Daga A, Rodig NM, Terhal PA, van Binsbergen E, Eid LA, Tasic V, Rasouly HM, Lim TY, Ahram DF, Gharavi AG, Reutter HM, Rehm HL, MacArthur DG, Lek M, Laricchia KM, Lifton RP, Xu H, Mane SM, Sanna-Cherchi S, Sharrocks AD, Raught B, Fisher SE, Bouchard M, Khokha MK, Shril S, Hildebrandt F. Mutations of the Transcriptional Corepressor ZMYM2 Cause Syndromic Urinary Tract Malformations. Am J Hum Genet. 2020 10 01; 107(4):727-742. PMID: 32891193.

Published on 3/24/2020

Pisarek-Horowitz A, Fan X, Kumar S, Rasouly HM, Sharma R, Chen H, Coser K, Bluette CT, Hirenallur-Shanthappa D, Anderson SR, Yang H, Beck LH, Bonegio RG, Henderson JM, Berasi SP, Salant DJ, Lu W. Loss of Roundabout Guidance Receptor 2 (Robo2) in Podocytes Protects Adult Mice from Glomerular Injury by Maintaining Podocyte Foot Process Structure. Am J Pathol. 2020 04; 190(4):799-816. PMID: 32220420.

Published on 11/21/2019

Stephen Berasi, Janet Elizabeth Buhlmann, Eric M. Bennett, Nathan Higginson-Scott, Huilan Gao, Zong Sean Juo, Stefano V. Gulla, Christine Huard, Sreekumar R. Kodangattil, Jian Li, Weining Lu, Xueping Fan, David J. Salant. Anticorps anti-robo2, compositions, méthodes et utilisations. 2019.

View full list of 53 publications.