Weining Lu, MD

Biography

Dr. Lu is a Principal Investigator, Physician-Scientist, and Associate Professor of Medicine, Pathology, and Laboratory Medicine at Boston University and Boston Medical Center. 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. 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. 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) (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). Molecular genetics of kidney and urinary tract development and congenital anomalies of the kidney and urinary tract (CAKUT).
2). Podocyte biology & injury in podocytopathy and nephrotic syndrome. Pericyte biology & injury in renal fibrosis.
3). Discover new drug targets and novel therapeutics for patients with podocytopathy, proteinuric kidney diseases, diabetic kidney disease, and cardiovascular and neovascular retinal eye diseases.
4). Develop new biomarkers and artificial intelligence-based digital pathology tools to improve the diagnosis and clinical trials of cardiovascular–kidney–metabolic (CKM) and neovascular retinal eye diseases.
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).

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

VISION STATEMENT of Dr. Lu’s laboratory on scientific research 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 medical and biomedical innovation ecosystem and society at large.
CORE VALUES: Curiosity, Innovation, Respect, Anti-bias, Focus on outcomes, Hard work, Perseverance, Honesty, Fair play, Courage, Integrity.

CURRENT LAB MEMBERS:

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

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

Yash Patel (PhD, Amanbhai Patel College of Pharmacy, CHARUSAT University), Postdoctoral Research Fellow. Working on the clinical pharmacy of novel therapeutics for kidney and eye diseases in Lu Lab, ypatel3@bu.edu.

Aarushi Dabas (BS in Biology and Child Studies & Human Development, Tufts University), Research Assistant working on the Biomarker Project with the Lu and Waikar Labs, assisting with the development of the MSD immunoassay for novel biomarkers in kidney, cardiovascular, and eye diseases. adabas20@bu.edu

Maura Dodge (MS in Population Health Research and Epidemiology at BU School of Public Health, BS in Biology at Saint Michael’s College), PhD student at BU Chobanian & Avedisian School of Medicine, Graduate Medical Sciences (GMS), Program in Biomedical Sciences (PiBS). Maura is currently performing a rotation research project in Lu Lab titled “Evaluate the role of novel SLIT/ROBO therapeutics in developing kidneys in a pre-clinical animal model,” mcdodge@bu.edu

Ryan Chahal (Third Year [M3] Medical Student at Boston University Chobanian & Avedisian School of Medicine). Research project: “Molecular control of kidney macula densa cell development”. Current BU MD medical student, chahalry@bu.edu

Laura Dodd (Biology Major, BU College of Arts and Sciences), Currently taking the Biology undergraduate research project course in Lu Lab titled “Studying SLIT2 expression in an animal model of chronic kidney disease” (Course BI350: Junior Research in Biology, four academic credits), ldodd02@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 BU School of Medicine MD program. Competed a BU Biomedical Engineering Senior Project in Lu Lab titled “Digital Biopsy for Glomerular Ultrastructural Measurement in Transmission EM Images” (Course: ENG BE465, two academic credits, and ENG BE466, four academic credits). Current BU Medical Student, alaudon@bu.edu

Easton Liaw (Human Physiology Major, Boston University Sargent College of Health and Rehabilitation Sciences), pre-medical student, BU Undergraduate Research Opportunities Program (UROP), Research project title: “A New Biomarker for Chronic Kidney Disease”, eliaw@bu.edu

Jiayi Amy Ji (Biochemistry & Molecular Biology Major, Boston University College of Arts and Sciences). Undergraduate Research Project in Lu Lab titled “Study the 3-D morphology of Kidney Glomerular Structure in an Animal Model of Chronic Kidney Disease”, amy2003@bu.edu

Harshita Pattam (Boston University 7-Year Combined Liberal Arts / Medical Education Program). BU Undergraduate Research Opportunities Program (UROP), Research project title: “Analyzing a Mouse Model of Congenital Anomalies of the Kidney and Urinary Tract.” Current BU BA/MD student, hpattam@bu.edu

Winston Tan, a BS/MD student currently in the 8-year Human Physiology and the Modular Medical/Dental Integrated Curriculum (MMEDIC) early acceptance program at Boston University. Working on the Inaugural BU Biomedical Innovation Technologies Affinity Research Collaboratives (BIT-ARC) research project to develop an artificial intelligence (AI) based digital pathology diagnostic tool for kidney disease, tanw@bu.edu

Omer Ege Vurkac is an undergraduate BU student majoring in Human Physiology at Boston University Sargent College. He is performing a research project in Lu Lab titled “Study Cardiorenal Syndrome in a mouse model of proteinuric chronic kidney disease.”

Kun Angel Yan (BU undergraduate student majoring in Biology, College of Arts and Sciences. She is currently a student research assistant at Lu Lab, working on pre-clinical animal models of proteinuric kidney disease. angelyk@bu.edu

Sarayu Chandiri is an undergraduate student majoring in Biology with a specialization in Cell Biology, Molecular Biology & Genetics at the Boston University College of Arts and Sciences. sarayuc@bu.edu

Simran Raikundalia (BU Presidential Scholar, Biochemistry & Molecular Biology (BMB) Major, BU College of Arts and Sciences), Currently taking the BMB undergraduate research project course in Lu Lab titled “Studying the molecular mechanisms of chronic kidney disease animal models with single-cell RNA sequencing technology” (Course BB340: Junior Research in BMB, two academic credits), simranr@bu.edu

Adhya Ramganesh (Boston University 7-Year Combined Liberal Arts / Medical Education Program). BU Undergraduate Research Opportunities Program (UROP), Research project titled “Non-invasive measurement of renal function in a pre-clinical animal model of chronic kidney disease.” Current BU BA/MD student, adhyasub@bu.edu

Sedef Yurdakul (BU Trustee Scholar, Human Physiology Major, BU Sargent College), pre-medical student, BU Undergraduate Research Opportunities Program (UROP), Research project title: “Validate a new biomarker for lupus nephritis and animal model of proteinuric kidney disease”, sedefyur@bu.edu

GRADUATED FORMER PHD STUDENTS:

Hila Milo Rasouly (PhD, Graduate Program in Genetics and Genomics, Graduate Medical Sciences, Boston University 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, Boston University School of Medicine). PhD thesis title: “Functional characterization of the SLIT2-ROBO2 signaling pathway in the podocyte”.

GRADUATED FORMER MS STUDENTS:

Tou S. Thao (MS in Medical Sciences Program, Graduate Medical Sciences, Boston University 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)”. Medical Student at the University of Minnesota Medical School. Current PGY1 Emergency Medicine Resident Physician.

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