Name: Amar J. Majmundar, MD, PhD

Institution: Boston Children’s Hospital, Harvard Medical School

Grant: 2020 Norman Siegel Research Scholar Grant

Project Title: Dissecting the Molecular Pathogenesis of NOS1AP and TRIM8 Mutations in Monogenic SRNS/FSGS.

How would you sum up your research in one sentence?

• I will investigate the biological mechanisms by which human mutations cause disease in children with severe kidney disease, specifically, nephrotic syndrome.

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

• I will use proteomics approaches in cultured podocytes to identify the interactors of NOS1AP and ubiquitin substrates of TRIM8 that are altered by human mutations in genes encoding these proteins. I will investigate the role of these downstream proteins in regulating the cellular functions of NOS1AP and TRIM8. I will investigate mouse models of NOS1AP- and TRIM8-associated nephrotic syndrome.

What inspired you to focus your research in this area?

• I have always been excited by the genetic basis of pediatric disease from early on in my medical and graduate training, because genetic causes provide us a starting point for understanding the biological mechanisms of disease and applying that understanding to patients directly. I was inspired by the patients with severe nephrotic syndrome, whom we care for in our renal service and who show great perseverance despite the challenges posed by their disease. When deciding on my fellowship laboratory, I was inspired by the research of my mentor Friedhelm Hildebrandt, MD. His career has focused on describing the genetic landscape of pediatric renal diseases. I was excited by the direct connection of his work to understanding basic kidney disease mechanisms.

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

• Understanding the genetic basis of renal diseases has many implications for patients. By making a molecular diagnosis, that can spare the patient further diagnostic workups that are unnecessary and focus the physician on necessary evaluations related to the genetic cause. The molecular diagnosis can also often provide prognostic information based on the natural history of other patients with similar gene mutations. With my research, I hope to develop a deeper biological understanding of two genetic forms of nephrotic syndrome. In the long-term, I believe this knowledge could be important in developmental potential therapies for patients.

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

• In the next decade of my career, I plan to become an independent physician-scientist who leads a laboratory focused on the pathogenesis of genetic forms of nephrotic syndrome in children and, also, cares for children with kidney disease as a pediatric nephrologist.

What has surprised you most about your career?

• I was not planning to do nephrology when I started my pediatrics training but was immediately drawn to it because of my experiences working with our pediatric nephrologists at Boston Children’s Hospital and caring for nephrology patients.

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

• I encourage all post-doctoral fellowship researchers to apply for this grant for two reasons. In writing the grant, it focuses you on what is most critical in developing your future research career: what you want to study, what mentorship and resources you need, what experimental approaches you should employ, etc. The award itself will provide critical support to help you begin your career and, in fact, carry out the ideas you thought hard about and proposed in the grant writing process.

Something you may not know about me is…

• I am a huge NBA fan and am excited for the season to resume when its safe to do so.

In my free time I like to…

• Spend time with my wife and kids.