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Across the Pacific Ocean, in the closely guarded temple for the Qin Shihuang, emperor of China, a golden figure stands tall. His name is Lu Bu and his back is made of bronze. He’s not just a statue, though. He’s a figure that guards the tomb of Qin Shihuang.
Dr. Lu’s translational research program has adopted combined human and mouse molecular genetics approaches to identify a number of 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, with the aim of using gene mutations, genomic imbalances and chromosomal rearrangements as signposts to identify disease-causal genes (reverse genetics) (Ref 2). Thereafter, molecular identification and analysis of disease genes as well as 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 humans and mouse models. Concurrently, the phenotype of knockout and transgenic mouse models will be studied 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 using biomedical research techniques in molecular genetics, developmental biology, protein biochemistry, molecular biology, pathology, and pharmacology. 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).