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January 9, 2023

Lupus Nephritis: New Approach Could Pave the Way for Innovative Treatments

When Jessica Hamerman, PhD, was perusing research papers in 2021, one discovery stopped her in her tracks — and ultimately put her on a whole new research path. 

The study introduced a potential new paradigm in treating lupus-related kidney disease (lupus nephritis). It detailed how researchers at St. Jude Children’s Research Hospital found immune cells called patrolling monocytes in the kidneys of people with lupus nephritis. This was surprising because scientists had no idea this type of cell — or the entire branch of the immune system that they come from — was involved in lupus nephritis.  

“Most lupus nephritis research has focused on cells in a part of the immune system called the adaptive immune system. But patrolling monocytes are part of a completely different part of the immune system, the innate immune system,” Dr. Hamerman says. “That means this finding could open up entirely new ways to treat the disease.”

What's more, the same study showed that blocking patrolling monocytes prevented lupus nephritis in lab models. That means this cell type could open the door to new therapies. This is important because about half of people with lupus develop lupus nephritis, which happens when immune cells mistakenly attack the kidneys. Available treatments don’t work for everyone, and without effective treatment, lupus nephritis can lead to kidney failure. 

Now Dr. Hamerman is teaming up with BRI genetics expert John Ray, PhD. Together, they’re examining if certain genes allow patrolling monocytes to move into the kidneys — and if blocking those genes could treat or even prevent lupus nephritis. 

Teaming up on an innovative research approach

Drs. Hamerman and Ray will combine their unique skill sets to examine and manipulate genes in lifelike models. This approach has never been done at BRI and is very new in immunology. 

First, Dr. Hamerman will build an innovative lab model that will allow them to look more closely at a subset of genes to see which ones are expressed in monocytes. Then, Dr. Ray will use CRISPR, a Nobel prize-winning gene-editing tool, to examine how various genetic changes in that model impact patrolling monocytes. This should help them identify which genes help control patrolling monocytes — and if blocking certain genes could stop or prevent lupus nephritis. 

“My work focuses on using genomic tools to understand disease, while Jessica is an expert in the underlying biology of lupus and building models to replicate the disease in the lab,” Dr. Ray says. “We hope that combining our unique skill sets can make a big impact.”

They also plan to examine parts of the genome (where your genetic material is stored) called “regulatory regions.”  

“Regulatory regions are regions of the genome that don’t contain any genes, but because your DNA is so tightly coiled, genes can brush up against them, helping facilitate how much or how little a nearby gene is expressed,” Dr. Ray says. 

From there, they hope to take their findings back to actual people, to see if patterns they find in the lab model also exist in blood samples from people with lupus.

“The model allows us to manipulate the genes and show cause and effect in a way that’s not possible in human samples,” Dr. Hamerman says. “Then we can use human samples to check our work and verify that what we’re seeing in the lab model is true in people with lupus and in human cells from healthy donors.” 

Using the latest in immunology to make a big impact

The research team is just getting this work up and running, but they’re excited to see what they find. This type of study, combining advanced lab models with genome editing, could shed light on why patrolling monocytes end up in the kidneys and how to stop them — and it will bring a new research method to BRI that could be used across immune system diseases.  

“This approach is on the leading edge of what immunologists are capable of,” Dr. Ray says. “It could really open up BRI’s ability to study disease processes and break them down in a way that allows us to see which genes are involved and why. I think it will be hugely impactful.”

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