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 […]
Author: mmahjoub
Ewa’s paper is published in EMBO Reports!
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 […]
Tao’s paper is published in Development!
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 […]
Ewa and Tao’s manuscripts are accepted!
Congrats to Ewa and Tao for having their papers accepted for publication in EMBO Reports and Development, respectively!
A big welcome to our new Summer Scholar Arushi Katyal!
Arushi is a sophomore at Boston College, and is joining the lab for 2 months as part of the WU Pediatric Center of Excellence in Nephrology (PCEN) Summer Scholar program. She will be investigating how defects in centrosome biogenesis affect the immune response during embryonic kidney development. Welcome to the lab!
Ewa’s new preprint about the effects of Cep120/centrosome loss in the kidney stromal progenitors is now on bioRxiv
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 […]
Tao’s new preprint on the consequences of Cep120/centrosome loss in nephron progenitors during kidney development is now on bioRxiv
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 […]
New collaboration with WU Ciliopathy Group colleagues on DNAAF5 gene dosage is published in JCI Insight
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 […]
Our collaboration on roles of GEMC1/MCIDAS during multiciliogenesis is published in Cell Death and Disease
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 […]
Moe, Megan and Tao attend the FASEB Cilia 2022 conference
Tao Cheng gave a wonderful talk titled “Developmental defects caused by centrosome dysfunction during kidney morphogenesis”.
Our review titled “Development of a Multiciliated Cell” is published in Current Opinion in Cell Biology!
Multiciliated cells (MCC) are evolutionary conserved, highly specialized cell types that contain dozens to hundreds of motile cilia that they use to propel fluid directionally. To template these cilia, each MCC produces between 30 and 500 basal bodies via a process termed centriole amplification. Much progress has been made in recent years in understanding the […]
Our collaboration on the role of Cep120 in axon development is published in Cell Reports
Microtubule (MT) modifications are critical during axon development, with stable MTs populating the axon. How these modifications are spatially coordinated is unclear. Here, via high-resolution microscopy, we show that early developing neurons have fewer somatic acetylated MTs restricted near the centrosome. At later stages, however, acetylated MTs spread out in soma and concentrate in growing […]
Welcome to our new research assistant Chidera Agwu!
Chidera did his undergraduate studies at Saint Louis University (MO), receiving his Bachelor of Science degree in Neuroscience. He will be investigating how defects in centrosome biogenesis and structure affect embryonic kidney development. Welcome to the lab!
Welcome to our new graduate rotation student DeHaven McCrary!
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!
Welcome our new postdoc Dr. Maneesha Pandey!
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’re recruiting – multiple positions available.
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 lab is awarded a 3-year grant from the Department of Defense!
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 […]
Our NHLBI grant is renewed for another 4 years!
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 […]
Introducing our new rotation student, Jennysue Kasiah
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!
Welcome to our new postdoc Dr. Ewa Langner!
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!
Rashmi’s paper is published in eLife!
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 […]
Our paper about centriole appendages is published in Nature Comm.
This study was led by Jadranka Loncarek’s group (NIH). They used correlative super-resolution (STORM) microscopy and TEM tomography to characterize the organization of centriole distal appendages in various ciliated cells. The study, titled “High-resolution characterization of centriole distal appendage morphology and dynamics by correlative STORM and electron microscopy” is available online at Nature Communications.
NIH funded postdoc position focused on cystic kidney diseases
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. […]
Moe presents our recent work at ASCB… and meets up with Erica!
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, […]
Our recent paper is highlighted in Nature Reviews – Nephrology.
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 […]
The analysis of new mutations in RTTN is published.
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.
Welcome to our visiting professor, Dr. Elif Firat-Karalar
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 […]
Lai Kuan and Kyuhwan’s paper is published in JCB!
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 published in eLife. Congratulations Ewelina!
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 ).
Moe visits his old lab at SFU
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.
Our second collaboration with Dr Hodzic on Nesprin1 is published.
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.
Mahjoub lab receives pilot grant from the ICTS!
Thanks to the ICTS for their generous support.
Our paper on Nesprin1 is published in Current Biology
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.
Our paper on the PAK4 inhibitor is published in KI
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 […]
Mahjoub lab receives award from Children’s Discovery Institute!
Thanks to the CDI for their generous support.
The Mahjoub lab receives Translational Innovation Award!
Thanks to the Washington University Nephrology Division for their generous support.