The Dr. William E. Paul Distinguished Innovator Award ($1M over 4 years) provides outstanding scientists with substantial support to conduct novel research into the fundamental causes of systemic lupus erythematosus.
2020 funded grant
Jacques Banchereau, PhD
The Jackson Laboratory for Genomic Medicine
Many of the common drugs used to treat systemic lupus erythematosus (SLE) focus on decreasing inflammation, which is a late symptom of the disease. While these drugs bring some relief, scientists and clinicians have been working instead to identify the root cause of lupus so they can stop the disease before major damage occurs. Roughly 20 years ago, Dr. Jacques Banchereau identified a clue to this mystery when he found that people with high SLE disease activity have an increased number of a specific type of immune cell known as classical dendritic cells. A number of genes that have been associated with lupus are active in these cells, but their function is not fully known. At the time of the initial discovery, the technology did not exist to further study these dendritic cells. The Distinguished Innovator Award will allow Dr. Banchereau to use today’s cutting-edge technology to isolate these dendritic cells from lupus patients and investigate their potential role as the initiators of the cascade of immune disease that characterizes SLE.
“Our work indicates that classical dendritic cells may be the root of all of the trouble suffered by people with lupus,” said Dr. Banchereau. “This award will help us confirm if this is the case, and if so, we hope it will point to potential treatment approaches that could stop the problem at its source.”
2020 funded grant
Ignacio Sanz, MD
Emory University
B cells are the cells that make antibodies. Some of them make autoantibodies , which target own tissue for immune response. In healthy people, those cells that make autoantibodies are destroyed. But in lupus and other autoimmune disorders they are not, so the autoantibodies they make interfere with the body’s own tissues. Dr. Sanz studies how and why they are able to thrive in people with lupus.
He has found that even at a very early phase in their development, these B cells already have lupus-specific genetic changes that allow them to continue growing when they should be destroyed. This is especially true in African Americans with severe lupus. Dr. Sanz plans to use the Distinguished Innovator Award to further probe the genetic pathways that allow these misguided B cells to mature in lupus patients. This work should help researchers develop more personalized therapies and will build on Dr. Sanz’s earlier research in which he showed that a drug that eliminates B cells can be effective in treating lupus.
What this study means for people with lupus:
“Determining how B cells that make autoantibodies thrive in lupus patients, and in different ethnic and clinical subsets of patients, will help us devise more personalized and effective therapeutics,” said Dr. Sanz.
2019 funded grant
Fabienne Mackay, PhD
University of Melbourne, Australia
Our studies have found that some high-fiber diets can protect mice from type I diabetes and lupus, diseases that result when the immune system attacks patients’ own cells. When broken down by bacteria in the intestines, the food produces large amounts of fatty acids called butyrate and acetate that may reduce inflammation and induce other beneficial effects. We now plan to test whether diet is protective in lupus. We will feed mice that are prone to lupus different diets designed to increase the levels of butyrate, acetate, or other molecules that may reduce immune system attacks. However, the diets may not be enough. To give them a boost, we will also treat the animals with monoclonal antibodies that eliminate immune cells that cause tissue damage.
What this study means for people with lupus
“We plan to test a novel combination approach to reverse lupus in mice. We will treat the animals with molecules that kill off harmful immune cells and feed them diets that may protect against the disease. If the approach works in mice, clinical trials could test it in people.”
2019 Funded Grant
Vanderbilt University School of Medicine
“The Achilles heel of the harmful immune cells in lupus may be their metabolism. We will test two drugs being developed for cancer that target cells’ metabolism to find out if they reduce lupus symptoms in mice. If the drugs are beneficial, clinical trials could test them in patients with lupus.”
2018 Funded Grant
Nir Hacohen, PhD
Broad Institute, Inc.
About half of patients with lupus develop lupus nephritis, or lupus kidney disease. This complication is the leading cause of illness and death in patients with lupus. However, researchers don’t know which cells are injuring the kidneys. That’s what Dr. Hacohen’s project aims to determine. In a previous study, his lab analyzed the kidneys of patients with lupus kidney disease and discovered 21 types of immune cells, most of which are absent from healthy kidneys. With the Distinguished Innovator Award, they will extend this work and examine tissue biopsies from newly diagnosed patients to ascertain which of the 21 immune cell types are present in patients with the most or least severe kidney injury. This analysis will allow his team to determine which types are related to kidney damage, function, and response to therapy. The results will provide new targets for treatments, as well as new tools to predict whether patients will respond to treatment and to provide insight into their future kidney health.
What this study means for people with lupus:
Dr. Hacohen’s research seeks to determine which cells cause kidney damage in lupus. Identifying these cells could lead to new treatments that prevent this damage.
2018 Funded Grant
Vijay K Kuchroo DVM, PhD
Brigham and Women’s Hospital, Inc.
In lupus, immune cells known as B cells release proteins called antibodies that attack patients’ own tissues. But several types of immune cells, including regulatory T and B cells, can block production of these antibodies and prevent lupus development in mice. Dr. Kuchroo and his colleagues had previously found that regulatory T and B cells make a protein called fibrinogen-like protein 2 (Fgl2) that curbs B cells’ production of destructive antibodies. In their new study supported with the Distinguished Innovator Award, they will determine how Fgl2 prevents B cells from making antibodies that target patients’ tissues and how it protects against lupus. In addition, regulatory T and B cells carry proteins on their surface, including one known as TGIT, that act as on-off switches. TGIT also stimulates regulatory T and B cells to make Fgl2. Another aim of their study is to determine whether TGIT and similar protein switches have a role in the development of lupus. Their findings could suggest new approaches for treating lupus by stimulating regulatory T and B cells, possibly through TGIT.
What this study means for people with lupus
Harmful immune cells cause the symptoms of lupus, but helpful immune cells called regulatory T and B cells may prevent them. Dr. Kuchroo wants to find out more about how certain types of regulatory T and B cells work, which might reveal whether we can use them for lupus treatment.
2016 Funded Grant
Boris Reizis, PhD
New York University School of Medicine
Dr. Reizis and his team are pursuing a novel idea that could explain what causes lupus, why flares develop, and how a treatment might be developed to prevent the attack. It has been shown that billions of cells die every day in our blood
and release their DNA packaged into small containers called microparticles. they believe that the abnormal buildup of DNA in these microparticles can cause the immune attack to begin and that the microparticles may provide vehicles for the DNA to travel throughout the body, causing the immune system to attack specific organs in their wake.
What this study means for people with lupus
Dr. Reizis will study how the DNA-carrying microparticles form and how the body normally gets rid of this DNA. they also plan to develop techniques that eliminate this DNA to provide a basis for future lupus treatments.
