Biography
Dr. Lu is a Principal Investigator, Physician-Scientist, and Associate Professor of Medicine, Pathology, and Laboratory Medicine at Boston University (BU) and Boston Medical Center (BMC). He is also the Primary Mentor for medical students, graduate students, undergraduate students, fellows, postdocs, and junior faculty in the Nephrology Section Department of Medicine (DOM). Dr. Lu’s laboratory focuses on basic and translational research in nephrology and genetics, including kidney development, congenital anomalies of the kidney and urinary tract (CAKUT) and vesicoureteral reflux (VUR), podocyte biology and injury, pericyte biology, kidney fibrosis, ROBO/SLIT and ZEB signaling, pre-clinical animal models of kidney disease, as well as the discovery of new biomarkers, artificial-intelligence-based digital pathology tools to improve diagnosis and clinical trials, and novel drug discovery and development for chronic kidney and eye disease. His significant scientific contributions in the field of nephrology and genetics include (1) discovering ROBO2 as one of the causative genes for CAKUT and VUR (OMIM 610878), (2) identifying SLIT2/ROBO2 signaling as a novel drug target for proteinuric chronic kidney diseases, which functions as a negative regulator for podocyte adhesions in podocyte biology and injury, (3) creating the first animal model for autosomal dominant polycystic kidney disease (PKD1), and (4) discovering ZEB2 as one of the causative genes for glomerulocystic kidney disease and its essential role in kidney stromal progenitor cell differentiation and kidney 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 their world-class research into inventions and innovations that benefit humankind.” This successful Academia-Industry collaboration has led to clinical trials and the first licensing agreement between Pfizer and BMC/BU. Dr. Lu is the Chair of the Core Oversight Advisory Committee in the Department of Medicine, a Co-Director of the BU Clinical and Translational Institute (CTSI) R01 Proposal Writing Workshop, the Lead Director of the Inaugural BU Biomedical Innovation Technologies Affinity Research Collaboratives (BIT-ARC) and the new B4D-ARC (Biomarkers for Diagnosis and Drug Development - A Data Science Approach), and a voting member of the Boston University Institutional Biosafety Committee (IBC). He is also a fellow of the American Society of Nephrology and the International Society of Nephrology. Dr. Lu is an Academic Editor of the scientific journal PLOS ONE and a member of the NIH grant review study sections of various grant mechanisms, including R01, R21, R03, F32, RC1, RC2, RC4, R13, R15, U01, UH2, UH3, U24, U54, P01, P20, P50, and SBIR/STTR. Dr. Lu’s research program is supported by grants from the government (e.g., NIH, DOD), foundations (e.g., NKF, MOD), industry (e.g., Pfizer), and internal awards from BU/BMC (e.g., DOM, Evans Center, CTSI, Ignition Award). Dr. Lu completed his training in the Renal Division and Genetics Division at Brigham and Women’s Hospital, Harvard Medical School, before he was recruited to the BU/BMC Nephrology Section.
RESEARCH PROGRAM:
The primary research interests of Dr. Lu’s laboratory focus on basic and translational research in 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 congenital disability 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 new biomarkers, novel drug targets, and therapeutics for patients with cardiovascular–kidney–metabolic (CKM) and eye 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 also the leading cause of chronic kidney disease and kidney failure in children and young adults under 40 (Ref 3).
Dr. Lu’s basic and translational research program has adopted combined human and mouse molecular genetics approaches to identify developmental genes crucial in kidney and urinary tract development, as well as the pathogenesis of CAKUT. The first human molecular genetics approach involves studying patients with CAKUT and apparent genetic defects, utilizing gene mutations, genomic imbalances, and chromosomal rearrangements as signposts to identify disease-causing genes (reverse genetics) (Ref 2). Following this, molecular identification and analysis of disease genes, as well as mutation studies in affected patients with a familial pattern of CAKUT, will be conducted (forward genetics) (Ref. 2, 4). The second approach involves studying the temporal and spatial expression patterns of disease genes in both human and mouse models. Concurrently, the knockout and transgenic mouse models of human disease genes will be generated and examined to recapitulate the human disease phenotype. Once these disease genes (e.g., ROBO2, SLIT2, ZEB2) are identified and animal models are created, 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 5-9). The multidisciplinary research approach encompasses pre-clinical animal models, patient samples, and biomarker studies, utilizing various new biomedical technologies and research techniques in molecular genetics, developmental biology, protein biochemistry, molecular biology, pathology, pharmacology, and computational and data sciences. Dr. Lu’s basic and translational research program connects the bench and bedside. It has generated new knowledge of disease mechanisms of CAKUT and kidney disease after birth, which advances the discovery of novel drug targets and therapeutics for patients with chronic kidney disease (Ref 7-10).
CITED 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). 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) Kumar S, Fan X, Rasouly HM, et al. ZEB2 controls kidney stromal progenitor differentiation and inhibits abnormal myofibroblast expansion and kidney fibrosis. JCI Insight 2023, Jan10;(8)1:e158418. PMID: 36445780. https://insight.jci.org/articles/view/158418
(7) 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).
(8) 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).
(9) 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).
(10) 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
For current research projects and lab members, please visit the LU Lab website: https://sites-staging.bu.edu/lulab/
Biomedical research projects are available for students and postdoctoral researchers. For inquiries regarding these research opportunities, please contact Dr. Lu at wlu@bu.edu