Magdalena Riedl Khursigara, MD, PhD

2025 Ben J. Lipps Research Fellowship Award

Institution: Broad Institute

Project Title: Elucidating the Role of TMED7 in Trafficking of Misfolded Protein Mucin 1

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

My research focuses on identifying therapeutic targets for diverse monogenic kidney diseases by evaluating the role of cargo receptor-mediated trafficking in the secretory pathway.

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

Mucin 1 kidney disease (MKD) is a form of Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD) resulting in chronic kidney disease and kidney failure. MKD is characterized by the toxic accumulation of Mucin 1 owing to a frameshift mutation in the MUC1 gene (MUC1-fs). MUC1-fs misfolds and subsequently gets sequestered in organelles such as the Golgi compartment. The entrapment is mediated by a family of cargo receptors called TMEDs. Here we will study the role of TMED7, as our lab has identified this protein as having a major role in MUC1-fs entrapment, and its potential as a drug target for this devastating disease.

What inspired you to focus your research in this area?

As a pediatric nephrologist, I have seen many children with genetic kidney diseases with no treatment available. Their childhood is dominated by doctor's appointments and dialysis sessions instead of going to playgrounds and having fun. I remember that one child I was taking care of with atypical Hemolytic Uremic Syndrome (aHUS), a devastating disease leading to frequent disease relapses and loss of kidney function. He had been admitted to the hospital constantly, but when a new treatment became available (the C5 inhibitor eculizumab), he received a kidney transplant with prophylactic use of eculizumab. It was amazing to watch how his life changed, and he was able to be a child again. This patient inspired me to pursue the road of research.

What impact do you hope your research will have on patients?

We need more therapies for children with genetic kidney disease. We also need to speed up drug discovery. I plan to do that using multi-omics approaches, including optical pooled screens and CRISP knockout screens, and repurpose already existing drugs.

What are your career goals at the end of the grant period? Five years out? Ten years out?

I want to become a physician-scientist and combine both my passions, clinical work and research. I want to study the fundamental mechanisms of genetic kidney diseases and find modulators by understanding the mechanism and performing drug repurposing screens.

What are the major challenges to beginning a career in nephrology research today?

I think, it's just a long road to become a physician-scientist. Medical school, PhD, residency, fellowship, and now a post-doc, that is almost 20 years spent learning and developing skills. I think this pathway needs to be accelerated to make it more attractive for young people to choose a career in nephrology and science.

What advice would you give to others to encourage them to apply for this grant funding?

The same advice I give my kids almost daily. Try to do your best every day. Learn from both successes and failures and strive towards excellence.

Something you may not know about me is…

I'm an avid baker, and I mainly bake cakes, bread, and cookies from my home country Austria.

In my free time I like to…

Bake and explore nature, but honestly, as a parent, I spend most of my free time exploring playgrounds.