Moe R. Mahjoub, PhD

Bridge Grant Pilot Program

Institution: Washington University in St Louis

How would you sum up your overall research focus in one sentence?

The overall focus of my research is to define how the cytoskeleton regulates cell physiology, tissue formation, and organ development in mammals.

Provide a brief overview of the research project you will conduct with help from the grant.

This project aims to develop new therapies for the Nephronophthisis-related renal ciliopathies (NPHP-RC), a group of congenital kidney disorders caused by defects in the function of the centrosome-cilium organelle complex. There are currently no therapeutic options for NPHP-RC, therefore patients are at a greater risk of developing end-stage kidney failure at an early age. That is why there is an urgent need to study the underlying disease mechanisms and to identify new therapeutic targets. To address this, we established new preclinical NPHP-RC models in my lab, including transgenic mice and patient cell-derived kidney organoids, and identified pathways that we hypothesize are driving the cystic and fibrotic disease phenotypes. In this proposal, we aim to perform comprehensive preclinical evaluation of targeting these pathways using genetic and pharmacological tools, including the use of repurposed drugs and combination therapies.

What inspired you to focus your work in this area?

I have been interested in understanding the basic biology of cilia and centrosomes for most of my career – how they are built, how they function, and what happens when there is a mutation that impacts these key cytoskeletal structures. The kidney is particularly sensitive to defects in these organelles – variants in more than 60 genes essential for cilia or centrosome function result in cystic and fibrotic kidney diseases. Surprisingly, we still do not fully understand how defects in these organelles causes these renal disease syndromes, which is one major motivation for our research.

What impact do you hope your research will have on people with kidney diseases?

My hope is that the successful completion of this study will advance our understanding of the pathomechanisms of NPHP-RC from descriptive to applied/therapeutic standpoints, and provide a strong rationale for advancing these specific therapeutics for testing in clinical trials. This is badly needed because, as of now, there are no FDA approved drugs for the NPHP-RC.

What has surprised you most about your career?

The life of an academic scientist is much more of a roller-coaster than I ever imagined.

What are the major challenges facing nephrology research today?

I know it's cliché, but funding is the biggest challenge by far. At a time when the nephrology field is making big advances in multiple areas, the current challenges at NIH and the reduction in federal funding are hurting the field in a big way.

In one sentence, please describe the importance of having grant funding available through KidneyCure.

Funding from KidneyCure has been a massive help – it was critical for me to retain the postdoctoral scholar working on this project, to provide the resources needed to continue acquiring data, and allow us time to develop this project further and resubmit our well-scored proposal to NIH/NIDDK.

Something you may not know about me is…

I used to be a professional DJ.

In my free time I like to…

Read (science fiction), listen to music (most genres except country), go on hikes with my dogs, sports (soccer and hockey), and travel (anywhere and everywhere I can!).