Category: Lab News

We are very fortunate to receive two R01 grants from the NIH, totaling $6.1 million over four years.  These awards will support investigations into genetic and acquired airway diseases linked to motile cilia dysfunction.  The studies feature a multidisciplinary approach and involved close collaborations with the Brody, Dutcher and Horani labs, as well as other […]

Maneesha talked about her research on the role of basal bodies in regulating cilia function in mammalian multiciliated cells.

First, I got to visit former postdoc Ewelina Betleja who is at the Max Planck Institute for Heart and Lung Research in Bad Nauheim. Was great hearing about her exciting new work in Thomas Braun’s group. Then went to Gottingen for an amazing conference on expansion microscopy… so much amazing science! Finally, got to visit […]

The Science Advisory Panel of the Polycystic Kidney Disease Foundation

The Ciliopathy Research Group at the summer BBQ

It was a fun conference in Pomona (CA). Susan and Steve were session chairs, while Amjad and Moe presented data from the group. Pubmed link

Primary ciliary dyskinesia is a rare monogenic syndrome that is associated with chronic respiratory disease, infertility, and laterality defects. Although more than 50 genes causative of primary ciliary dyskinesia have been identified, variants in the genes encoding coiled-coil domain-containing 39 (CCDC39) and CCDC40 in particular cause severe disease that is not explained by loss of […]

Ultrastructure expansion microscopy (U-ExM) involves the physical magnification of specimens embedded in hydrogels, which allows for super-resolution imaging of subcellular structures using a conventional diffraction-limited microscope. Methods for expansion microscopy exist for several organisms, organs, and cell types, and used to analyze cellular organelles and substructures in nanoscale resolution. Here, we describe a simple step-by-step […]

Autosomal dominant polycystic kidney disease (ADPKD) is a monogenic disorder accounting for approximately 5% of patients with renal failure, yet therapeutics for the treatment of ADPKD remain limited. ADPKD tissues display abnormalities in the biogenesis of the centrosome, a defect that can cause genome instability, aberrant ciliary signaling, and secretion of pro-inflammatory factors. Cystic cells […]

Mutations in genes that disrupt centrosome structure or function can cause congenital kidney developmental defects and lead to fibrocystic pathologies. Yet, it is unclear how defective centrosome biogenesis impacts renal progenitor cell physiology. Here, we examined the consequences of impaired centrosome duplication on kidney stromal progenitor cell growth, differentiation, and fate. Conditional deletion of the […]

Mutations that disrupt centrosome biogenesis or function cause congenital kidney developmental defects and fibrocystic pathologies. Yet how centrosome dysfunction results in the kidney disease phenotypes remains unknown. Here, we examined the consequences of conditional knockout of the ciliopathy gene Cep120, essential for centrosome duplication, in the nephron and collecting duct progenitor niches of the mouse […]

Congrats to Ewa and Tao for having their papers accepted for publication in EMBO Reports and Development, respectively!

Reciprocal signaling between progenitor cells of the stromal mesenchyme (SM), metanephric mesenchyme and ureteric bud is critical for proper mammalian kidney morphogenesis. Several of these signaling pathways are regulated by the centrosome, and its associated structure the primary cilium. Mutations in genes that disrupt centrosome biogenesis or function cause congenital kidney developmental defects and lead […]

Mutations that disrupt centrosome structure or function cause congenital kidney developmental defects and fibrocystic pathologies. Yet, it remains unclear how mutations in proteins essential for centrosome biogenesis impact embryonic kidney development. Here, we examined the consequences of conditional deletion of a ciliopathy gene, Cep120, in the two nephron progenitor niches of the embryonic kidney. Cep120 loss led to […]

DNAAF5 is a dynein motor assembly factor associated with the autosomal heterogenic recessive condition of motile cilia, primary ciliary dyskinesia (PCD). The effects of allele heterozygosity on motile cilia function are unknown. We used CRISPR-Cas9 genome editing in mice to recreate a human missense variant identified in patients with mild PCD and a second, frameshift […]

Multiciliated cells (MCCs) project dozens to hundreds of motile cilia from their apical surface to promote the movement of fluids or gametes in the mammalian brain, airway or reproductive organs. Differentiation of MCCs requires the sequential action of the Geminin family transcriptional activators, GEMC1 and MCIDAS, that both interact with E2F4/5-DP1. How these factors activate […]

DeHaven did his undergraduate studies at  Westminster College (MO). He then completed a Master of Science degree in Physiological Sciences at the University of Arizona, where he studied the role of microtubule associated proteins in GLUT4 translocation during insulin stimulation . He will be investigating microtubule dynamics and reorganization during stem cell differentiation. Welcome to the lab!

Maneesha did her graduate studies with Dr. Cynthia He at the National University of Singapore. She studied the role of an arginine kinase and the lipidated protein intraflagellar transport (LIFT) pathway in cilia of Trypanosoma brucei. She will be studying cellular pathways that regulate centrosome-cilia protein trafficking. Welcome to the lab!

We are looking for postdoctoral fellows, graduate students and research assistants interested in the biology of microtubules, centrosomes and cilia. Our lab investigates how mutations in centrosomal and ciliary genes disrupt normal cell physiology, leading to human disease syndromes called “Ciliopathies”. These include cystic-fibrotic kidney diseases, and respiratory/airway defects such as Primary Cilia Dyskinesia. Multiple […]

The Mahjoub lab has received a 3-year, $1.83M Investigator-Initiated Research Award from the Department of Defense – Congressionally Directed Medical Research Program. The project is titled “Targeting Centrosome Clustering as a Novel Therapy for Autosomal Dominant Polycystic Kidney Disease“.  This project focuses on the preclinical evaluation of small molecule inhibitors that target centrosome clustering as a […]

This grant involves a close collaboration with Dr. Susan Dutcher, Professor of Genetics, Cell Biology and Physiology, and Dr. Steven Brody, the Dorothy R. and Hubert C. Moog Professor of Pulmonary Medicine. We received a four-year, $3.14 million RO1 renewal grant from the National Heart, Lung, and Blood Institute (NHLBI) to study the “Regulation of Motile Cilia […]

Jennysue will be using cutting-edge imaging techniques, including expansion and superresolution microscopy, to study mechanisms that regulate centriole biogenesis and ciliogenesis in multiciliated cells. Welcome to the lab!

Ewa received a Bekker Programme postdoctoral fellowship from the Polish National Agency for Academic Exchange, and will be studying metabolic changes in Autosomal Dominant Polycystic Kidney Disease. Welcome to the lab!

Congratulations to first author Rashmi Nanjundappa, as well as former lab member Kyuhwan Shim, for their recent publication. This was a wonderful collaboration with Jadranka Loncarek (NIH) and her postdoc Dong Kong, as well as Steve Brody (Washington University) and Tim Stearns (Stanford). The study, “Regulation of Cilia Abundance in Multiciliated cells” can be found […]

An NIH (T32)-funded postdoctoral position is available in the Mahjoub Lab (Division of Nephrology, Washington University in St. Louis) to study the consequences of centrosomal defects during kidney development and homeostasis. Our group investigates how mutations in centrosomal and ciliary genes disrupt embryonic kidney development and cause renal Ciliopathies including Polycystic Kidney Disease and Nephronophthisis. […]

This was a reunion with the very first member of my lab, Erica Silva. She was an undergrad in Tim Stearns’ lab when I was a postdoc, and joined me when I moved to Washington University. She helped me setup the lab, start experiments, and train the first crew. We published the very first paper from the lab, […]

This study was a large collaboration between labs at UC Davis, Kansas University, University of Colorado and Washington University in St Louis. The project discovered that arginine auxotrophy is a key feature of autosomal dominant polycystic kidney disease (ADPKD). The results suggest that dietary arginine depletion, or targeting of the arginine metabolic pathway, may be a new therapeutic avenue in […]

This was a great collaboration with the labs of F. Sessions Cole III (Dept. of Pediatrics), Susan Dutcher (Genetics) and Thomas Ferkol (Pediatrics). The study titled “Functional characterization of biallelic RTTN variants identified in an infant with microcephaly, simplified gyral pattern, pontocerebellar hypoplasia, and seizures” can be found here.

Elif is Moe’s former lab-mate from Stanford, when they were both postdocs in Tim Stearns’ lab. She is now an Assistant Professor at Koc University in Istanbul (Turkey), working on deciphering the functions of centrioles satellites in mammalian cells. She will be spending a month with us here at WashU. You can visit here lab […]

Congratulations to co-first authors Lai Kuan Dionne and Kyuhwan Shim, as well as Tao Cheng, for their recent paper. It was a lot of hard work and the project took over 3 years to complete. This was a wonderful collaboration with Sanjay Jain (WU Nephrology) and his lab members Masato Hoshi and Amanda Knoten, as […]

Ewelina’s paper is now online at eLife. The study shows the presence of an active mechanism that regulates centrosome homeostasis during quiescence, mediated by Cep120.(https://elifesciences.org/articles/35439 ).

It was very nostalgic to go back to Simon Fraser University, and walk the hallways again. Plus, it’s always great to see my old graduate mentor Lynne Quarmby.

This project was led by Dr. Didier Hodzic in the Opthalmology Department at Washington University.  The manuscript was published in Neurobiology of Disease and can be found here.

Thanks to the ICTS for their generous support.

This project was led by Dr. Didier Hodzic in the Opthalmology Department at Washington University. The study defined a novel function for the nuclear envelope-associated protein Nesprin1 at centriolar rootlets of various ciliated cell types. The manuscript was published in Current Biology and can be found here.

This was a large collaboration between labs at UC Davis, China Medical University, University of Kansas, Washington University in St Louis, and Karyopharm Therapeutics. This study characterized a new small molecule inhibitor of PAK4 that specifically kills cystic renal epithelial cells, and is now being evaluated in a clinical trial. The manuscript was published in Kidney International and […]

Thanks to the CDI for their generous support.

Thanks to the Washington University Nephrology Division for their generous support.