Name: Naoka Murakami, MD PhD

Institution: Brigham and Women's Hospital

Grant: Carl W. Gottschalk Research Scholar Grant (2019)

Project Title: Roles of Immune Checkpoint Signaling in Autoimmune Kidney Diseases
 

How would you sum up your research in one sentence?

• My research focuses on how immune system can tell between self and non-self using novel transgenic animal models.
   

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

• The overall goal of my research project is to dissect the mechanisms of tolerance against kidney-restricted antigens. We hypothesize that tolerance in the kidney is regulated by co-stimulatory molecules expressed in antigen-specific T cells and their ligands found in kidney parenchymal cells or antigen presenting cells; and that disruption of tolerance would lead to maladaptive inflammation in the kidney. To test this hypothesis, we will investigate T cell tolerance mechanism at steady state and characterize kidney-infiltrating pathogenic T cells, with combination of novel transgenic animals and tetramer-based approach. This will represent unique preclinical tools, which will lead to identification of novel therapeutic targets.
   

What inspired you to focus your research in this area?

• I have always been amazed by how our body can recognize self from non-self. Immune system is a collective memory of encounters to self and non-self (e.g. viruses, bacteria, cancer neo-antigens) and it should work to prevent autoimmunity. In the beginning of fellowship, I had a patient with melanoma who developed very severe interstitial nephritis after receiving immune checkpoint inhibitors and I was stunned by how easily this tolerance to self-antigens could be broken. This inspired me to develop my current research project to study mechanism of tolerance to kidney-specific antigens.
   

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

• I hope my work will lead us to better understand immune regulation against self-antigens and allo-antigens in the kidneys. Ultimately, this knowledge will help develop therapeutics for patients with autoimmune kidney diseases as well as transplant recipients.
   

What are your short and long-term career goals?

• By the end of the grant period, I will be more skillful in data analysis, have answered my questions and develop more collaborative works. In five to ten years, I hope to be an independent scientist to study self-tolerance in autoimmune kidney diseases and transplant. In addition, I wish to grow as a scientist who supports junior scientists/students, as my mentors have been doing for me!  
   

What has surprised you most about your career?

• I started my research career in biochemistry field, studying bioactive lipids and their signaling pathways. I am pleasantly surprised that my clinical and research career path evolved to study immune system in autoimmune kidney diseases. I am thrilled to have more surprises coming forward!
   

What are the major challenges facing nephrology research today?

• Lack of fundamental understanding of disease process, especially for relatively rare autoimmune kidney diseases (e.g. lupus nephritis, membranous nephropathy, primary podocytopathy). Without mechanistic understanding, developing therapeutics might not be easy. Through my research, I hope to provide scientific evidence to uncover some of disease mechanisms to help develop therapeutics.
   

Something you may not know about me is…

• I have a sweet tooth.
   

In my free time I like to…

• Spend time with my son, travel, eat sweets.