Weining Lu, MD
|Institution||Boston University School of Medicine|
|Address||650 Albany St|
Boston MA 02118
|Institution||Boston Medical Center|
The primary research interests in Dr. Lu’s laboratory focus on three scientific areas: 1. Genetics of normal renal tract development (Ref 1); 2. Genetics of kidney and urinary tract birth defects (Ref 2); 3. Biological functions of renal tract birth defect genes and their roles in common kidney diseases (Ref 3, 4). Congenital anomalies of the kidney and urinary tract (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) (Ref 1). 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 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 renal tract development and pathogenesis of CAKUT. The first human molecular genetics approach is to study individuals with CAKUT and apparent genomic 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). 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). 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 (Ref 3). This multidisciplinary approach includes the application of human and mouse genetics, developmental biology, biochemistry, molecular biology, pharmacology and experimental therapeutics, 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 can result in novel therapeutics for patients with common kidney diseases. 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.
1. Rasouly HM, Lu W. Lower urinary tract development and disease. Wiley Interdiscip Rev Syst Biol Med 2013; 5:307-42.
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.
3. 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.
4. 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:e24763.
- Chronic kidney disease
- Kidney and urinary tract development
- Lower urinary tract development and disease
- Podocyte biology
- Slit-Robo signaling pathway
- Vesicoureteral reflux (VUR)
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