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Lupus Mechanisms and Targets Award (LMTA)

The Lupus Mechanisms and Targets Award ($600,000 for 3 years) supports research focused on the identification and/or investigation of molecular pathways or targets that could lead to new or improved therapies for people with lupus.

If you are a researcher and would like to learn more about our funded research please click here.

2020 Funded Grant

 

Marcus Clark, MD
The University of Chicago

 

Inflammation of the kidneys is one of the most severe complications of lupus. It affects about half of lupus patients, and often proceeds even when the patients are treated with strong drugs. Dr. Clark found that the immune reaction causing this inflammation does not happen in mouse models of lupus, so he had to find another way to study it. There are many types of cells in the kidney, and these cells can affect each other. Dr. Clark’s lab developed computer programs that can analyze images taken of kidney cells, finding the difference between when cells of different types are just resting next to each other peacefully versus when they work together to cause inflammation. Each person has a different mix of these cells, and the makeup of the mix can affect the course of disease.

 

With LRA’s Lupus Mechanisms and Targets Award, Dr. Clark hopes that by examining the precise mix of cells from the kidneys of lupus patients, and how they interact with each other, this technology can predict how each patient will fare. This also points to the possibility of developing personalized drugs that would help different patient groups.

 

What this study means for people with lupus

Customized maps of the cells causing inflammation in the kidneys of lupus patients could help doctors foresee how each person will progress and help researchers develop more personalized treatments.

2020 Funded Grant

 

Jessica A. Hamerman, PhD
Benaroya Research Institute at Virginia Mason

 

Antibodies come in a few different flavors. In lupus, antibodies against the body’s own tissues—called autoantibodies—clump up to form large immune complexes that cause organ damage in people with lupus, worsening the progression of disease. Most of the autoantibodies in the complexes are of one particular shape, called IgG. Though most research focus has been on how IgG in immune complexes causes disease in lupus, Dr. Hamerman’s group is studying a different type of autoantibody called IgA. She has also shown that these IgA’s stimulate the immune system in lupus.

 

In her future work funded with the Lupus Mechanisms and Targets Award, she plans to test if these newly discovered IgA autoantibodies are key in the development of lupus, and if so, if they might be targeted with new drugs.

 

What this means for people with lupus

Dr. Hamerman showed that a type of autoantibody, IgA, that has not been well studied before, is important in lupus. If IgA proves key in causing the disease, it may offer a good target for drug development.

2020 Funded Grant

 

Alessandra B Pernis, MD
The Hospital for Special Surgery

 

A  certain type of B cell has recently been identified that makes many of the autoantibodies which cause damage in people with lupus. Building on the knowledge that patients with more of these cells can have worse disease, Dr. Pernis  found some of the molecules that control the growth of these cells in mice. With her Lupus Mechanisms and Targets Award, she hopes to explore if these molecules, and this cell type, cause tissue damage in people with lupus.

 

What this means for people with lupus

This newly identified B cell subtype and the molecules that control these cells could serve as molecular markers to tell which patients are at risk of severe disease or may even serve as a target for new drugs.

2020 Funded Grant

 

Gregg J Silverman, MD
New York University School of Medicine

 

The microbiome is the community of bacteria, viruses, and fungi that reside in everyone’s body, in the gut and on our skin. A robust microbiome is essential for good health, and changes in the species that make up the microbiome have been linked to many different disease states. Dr. Silverman has found one particular species of bacteria that is present at high levels in the intestines of lupus patients with kidney disease. With his Lupus Mechanisms and Targets Award from the LRA, he will test if this strain of bacteria has a role in causing lupus.

 

What this means for people with lupus

Dr. Silverman has found a species of bacteria that is more prevalent in the gut of people with lupus than among healthy people who served as the control group. In his future work he hopes to see if detection of this species of bacteria might help in the earlier diagnosis of those at risk of developing kidney disease.

2020 Funded Grant

 

Roger Bryan Sutton, PhD
Texas Tech University Health Sciences Center

 

One of the processes that causes tissue damage in lupus patients is the generation of autoantibodies: antibodies that trigger inflammation. One part of the body that an autoantibody can react to is DNA, the genetic material inside your cells. If any DNA leaks out of cells —which happens sometimes in everyone—there is a special enzyme that cleans it up. But in some lupus patients, this enzyme doesn’t work well. Injecting it into people with lupus could possibly help them, but the injected enzyme wouldn’t  last for very long in the body.

 

With LRA’s Lupus Mechanisms and Targets Award, Dr. Sutton’s lab is planning to fortify this enzyme so it would last longer, which may allow it to be tested as a potential therapy for SLE.

 

What this means for people with lupus

Making a version of this enzyme that is long-lasting in the body could provide a treatment that would be effective without unpleasant side effects.

2019 Funded Grant

 

Montserrat Anguera, PhD
University of Pennsylvania School of Veterinary Medicine, Philadelphia

 

Women have two X chromosomes, but men only carry one. In women’s cells, one of the X chromosomes typically switches off most of its genes. We hypothesize that many of these genes turn back on in lupus. Because a large number of genes that control the immune system are on the X chromosome, switching them back on could cause the immune system to function abnormally. To test our hypothesis, we will measure whether silenced genes on the X chromosome have turned back on in cells from patients with lupus. We will then measure the effect of this reactivation on the immune system in mice and determine whether we can reverse it in cells from women with lupus.

 

The study and what it means for patients:

“Women are much more likely to develop lupus than are men, and the difference may be partly due to their chromosomes. Most genes on one chromosome in women normally shut down. We will test the hypothesis that some of these genes switch back on in lupus, disrupting the immune system. The work could reveal new targets for lupus therapies.”

2019 Funded Grant

 

Paolo Casali, MD
University of Texas Health Science Center at San Antonio

 

Our hypothesis is that the enzyme Tet2 stimulates B cells to make harmful antibodies, while the enzyme Sirt1 reduces their production.  To test our hypothesis, we will find out whether the levels of these enzymes are abnormal in B cells from mice and patients with lupus. We will also give lupus-prone mice chemicals that increase levels of Sirt1 or reduce levels of Tet2 and test whether the animals produce less of the destructive antibodies. Our project will also search for other molecules that inhibit Tet2 or stimulate Sirt1 that could be developed into lupus treatments.

 

What this study means for people with lupus

“In lupus, immune cells known as B cells release destructive proteins called antibodies that target patients’ own tissues. We will test whether two enzymes increase or reduce the amount of antibodies that B cells produce. We will also identify molecules that switch these enzymes on or off and that could be turned into lupus therapies.”

2019 Funded Grant

 

Hongbo Chi, PhD
St. Jude Children’s Research Hospital, Memphis, Tennessee

 

Follicular T cells are harmful in lupus because they spur other immune cells to release damaging proteins called antibodies. We have identified several metabolic differences between follicular T cells and other immune cells. Mitochondria, the structures that provide power for cells, are more active in follicular T cells, for instance.  We now plan to test mice to find out whether these differences are crucial for follicular T cells to function. We will also study mice that are missing key enzymes for metabolism to find out if they have less severe lupus symptoms.

 

What this study means to people with lupus

“Immune cells known as follicular T cells may be one of the main culprits in lupus. We have found that these cells have a distinctive metabolism. Our new work will try to discover whether the cells’ unique metabolism promotes development of lupus and whether targeting it is a possible approach for new treatments.”

2019 Funded Grant

 

Hui-Chen Hsu, PhD
University of Alabama at Birmingham

 

The harmful B cells in lupus develop from resting B cells that don’t release antibodies. Our goal is to prevent these resting cells from changing into destructive ones. We plan to test whether two immune system molecules that control B cells, interleukin-4 and interleukin-2, can stop the cells from becoming harmful. The first part of our study will test interleukin-4 and low doses of interleukin-2 on isolated cells from patients with lupus. If the two molecules prevent resting B cells from changing and curb antibody release, we will ask whether they are beneficial in mice with lupus. The next step, if results from those experiments are positive, could be clinical trials of interleukin-4 and low doses of interleukin-2 in patients with lupus.

 

What this study means for people with lupus

“The immune cells known as B cells release proteins called antibodies that lead to tissue damage in lupus. Using cells from patients and mice, we will ask whether two immune system molecules can reduce the numbers of harmful B cells and cut the amount of antibodies they release. If our study is successful, the two molecules could be tested as treatments in patients with lupus.”

2019 Funded Grant

 

Vicki Kelley, PhD
Harvard Medical School

 

The switch we identified is a protein called Ptprz that is made by kidney cells and immune cells. To reveal Ptprz’s role in kidney inflammation, we will study genetically modified, lupus-prone mice that lack the protein to find out if they have less inflammation. We will also give other lupus-prone mice a drug developed to treat brain cancer that blocks Ptprz. To find out whether Ptprz is important in lupus, we will analyze kidney tissue from patients with the disease and ask if people with more severe kidney damage produce more Ptprz.

 

What this study means to people with lupus

“We may have discovered a master switch that turns on kidney inflammation, which affects about half of patients with lupus. Our study will determine whether eliminating this switch or shutting it off protects the kidneys in mice. Our results could lead to clinical trials of drugs that turn off the switch.”

 

 

2019 Funded Grant

 

Jason Knight, MD, PhD
University of Michigan, Ann Arbor

 

Neutrophils, a type of immune cell, fight infections by squirting out DNA molecules known as NETs. In patients with lupus, neutrophils may be under stress, which could spur them to release their DNA even in the absence of an infection. Our study will test whether a networks of tubes in the cells known as the endoplasmic reticulum plays a key role in NET release. We suspect that the endoplasmic reticulum detects when neutrophils are under stress and then stimulates the cells to produce NETs. The research will test whether a stress-sensing protein in the endoplasmic reticulum spurs neutrophils from patients with lupus to release NETs. We will also ask whether molecules that block this protein reduce lupus symptoms in mice.

 

What this study means to people with lupus

“Some immune cells spray out their own DNA to trap bacteria, but in lupus this DNA can provoke the immune system to attack patients’ own cells. We aim to determine how a type of cell stress may lead to release of this DNA. Our research could point to new drug targets for treating lupus.”

2018 Funded Grant

 

Joseph Craft, MD
Yale School of Medicine

 

Immune cells called follicular helper T cells are enablers that allow B cells to produce autoantibodies (ANAs) that harm patients’ own tissues in lupus. A protein known as NFAT acts as a master switch to activate follicular T cells, turning the cells on and allowing them to function. We suspect that NFAT may work differently in follicular helper T cells in lupus, which could explain why B cells attack patients’ own tissues in the disease. To test our hypothesis, we will first analyze cells from healthy mice to determine how NFAT normally works. We will then test cells from mice and patients with lupus to see if and how NFAT functions changes in those with the disease. Drugs known as calcineurin inhibitors, now under study as treatments for kidney disease in lupus, inhibit NFAT and may prevent function of follicular helper T cells, although the precise mechanisms of how these drugs work are unclear. Our studies will test calcineurin inhibitors in mouse and human follicular helper T cells to determine whether they block the cells. The results of the proposed studies should help researchers better understand how T follicular cells may be improperly regulated in lupus and may point to new or improved therapies for lupus.

 

What this study means to people with lupus

“B cells damage patients’ own tissues, but they can’t launch their attacks without assistance from another type of immune cells called follicular helper T cells. We are trying to find out whether a certain protein allows these accomplice cells to behave differently in lupus and whether drugs under development will inhibit the function of the cells. A better understanding of how these partners operate can open new treatment avenues for lupus.”

2018 Funded Grant

 

Keith Elkon, MD
University of Washington

 

The study and what it means for patients:
“Current anti-malarial therapies like hydroxychloroquine are often used to treat lupus. We have developed a new drug that is similar to these anti-malarials, X6, that we believe is more effective and less toxic than current medications. With our Target Identification in Lupus grant, we are performing further tests of the drug’s safety and effects in human cells and in mice. If these tests are successful, we will move toward clinical trials of the drug in patients with lupus.”

 

Summary:
Drugs like hydroxychloroquine (HCQ) are used in 70-80 percent of patients with lupus to help provide relief of joint pain and skin rashes. HCQ is known to reduce cells’ production of type I interferons, immune system molecules that drive chronic inflammation and other symptoms of the disease. Our research recently uncovered an additional mechanism for how these drugs work in lupus. We have designed a new drug, X6, that we expect to be more effective and less toxic than current anti-malarial therapies. Our previous studies found that X6 reduced levels of type I interferons in mice. We now plan to rigorously test the drug to determine whether it is safe in human cells. We will also perform further studies of X6 in mice to determine how it circulates through the body and whether it is superior to HCQ. Positive results from these studies would allow us to perform further studies that could lead to a phase I clinical trial.

2018 Funded Grant

 

David Levy, PhD
NYU School of Medicine

 

The study and what it means for patients:
“We are investigating a strategy for treating lupus that may be just as effective as other drugs under development for the disease but with less suppression of the immune system.  We are focusing on drugs that are already approved or being tested for other diseases, which should speed the start of clinical trials for any of the drugs we find are promising.”

 

Summary:
Type I interferons are produced by the body in order to fight off viral infections. However, patients with lupus produce type I interferons even in the absence of infection, resulting in long-lasting inflammation, which can damage many different organs in the body. Our project will explore a novel strategy to reduce this chronic inflammation while sparing the normal responses to infection, which other lupus treatments under development to inhibit type I interferons may disrupt. Type I interferons work by stimulating other proteins that switch on certain genes, and we will test combinations of drugs that may block these genes from turning on in human cells. Our results could identify a set of drug combinations that reduce inflammation with the least impact on normal antiviral defenses. Because the research will focus on drugs that have already been approved for other conditions or are being tested in other diseases, we anticipate that this research could progress to clinical trials within three years.

2018 Funded Grant

 

Eric Meffre, PhD
Yale School of Medicine

 

We are investigating why patients with lupus fail to remove destructive B cells, called autoreactive B cells, that naturally form in the body. Some evidence suggests that a protein called PTPN22 may be responsible for this failure. Our preliminary studies of mice “humanized” with human lupus cells suggest that inhibiting PTPN22 could restore the ability to destroy B cells that attack patients’ own healthy cells. One goal of the proposed research is to find out more about PTPN22’s function in B cells, such as how it interacts with other molecules in the cells and how these interactions are affected by a specific mutation in PTPN22’s gene that increases patients’ risk of developing lupus. Those results might point to new ways to block PTPN22. We also intend to determine whether inhibiting PTPN22 stimulates the “humanized” mice to eliminate autoreactive B cells. Targeting PTPN22 to restore patients’ ability to remove autoreactive B cells may represent a unique approach to prevent lupus development and reduce autoimmunity.

 

What this study means for people with lupus

“We are testing whether a protein called PTPN22 prevents patients with lupus from destroying harmful B cells that can attack a person’s own healthy cells. Our findings could help researchers develop new lupus treatments that block PTPN22 and eliminate self-destructive B cells.”

2018 Funded Grant

 

Deepak Rao, MD, PhD
Harvard Medical School

 

The study and what it means for patients:

“In lupus, B cells can produce antibodies that damage patients’ own tissues—but only if the cells first interact with another type of immune cell called a helper T cell. We have discovered a new type of helper T cell that may provide the stimulation B cells need to start making self-destructive antibodies. The insights our work provide may allow development of new treatments for lupus that target these T cells.”

 

Summary:
Which helper T cells spur B cell cells to produce harmful antibodies in lupus is unclear. Recently, we discovered a new cell variety, the T peripheral helper (Tph) cell, that activates B cell responses and antibody production in patients with rheumatoid arthritis. These cells are also common in the blood of patients with lupus, and our study will ask whether they are important in the disease. Our project will determine how abundant the cells are in patients who have recently been diagnosed with the disease and how current immune-suppressing medications alter their numbers. We are also examining the types of B cell responses that Tph cells stimulate, as well as the chemical messages that promote formation of Tph cells and keep them functioning. In particular, we will ask whether a T cell protein known as the aryl hydrocarbon receptor helps activate Tph cells. These studies may identify new ways to interfere with the cells, such as by targeting the aryl hydrocarbon receptor, that could inhibit destructive immune responses and thus treat lupus.

2018 Funded Grant

 

Jillian Richmond, PhD
University of Massachusetts Medical School

 

The study and what it means for patients:
“Some patients with lupus develop a form of the disease that primarily affects the skin – cutaneous lupus. We are trying to determine what attracts harmful immune cells into patients’ skin and whether existing drugs can keep the cells out to prevent damage. These results could lead to clinical trials to test these drugs in patients with cutaneous lupus.”

 

Summary:
In patients with lupus, immune cells mistakenly attack the body’s tissues. The skin is their main target in people who have the cutaneous type of the disease. Earlier studies suggested that molecules known as chemokines trigger immune cells to infiltrate the skin, but the source of these molecules wasn’t clear. Using samples from the blisters on participants’ skin, we will identify the specific cells that produce the chemokines. To go one step further and test a possible therapeutic approach, we will then treat mice that develop lupus skin symptoms with several drugs known to inhibit the effects of the chemokines in different ways. Some of these drugs are approved for treating other diseases, such as rheumatoid arthritis. Our findings could indicate whether these drugs should be tested in patients with cutaneous lupus and may also enable researchers to develop new drugs that block the chemokines but have fewer side effects.

2018 Funded Grant

 

Nan Yan, PhD
University of Texas Southwestern Medical Center

 

The study and what it means for patients:
“Our cells carry carbohydrates that usually enable the immune system to recognize the cells as harmless. Our study is testing whether immune cells in patients with lupus mistake the carbohydrates on our cells for those of harmful microbes and launch attacks. Our findings could identify better ways to diagnose lupus and suggest potential treatments that stop the immune system from targeting the carbohydrates.”

 

Summary:
Bacteria and other microbes contain carbohydrates called glycans that allow the immune system to correctly identify them as enemies. All our own cells also carry glycans, which sometimes activate immune responses and may lead to chronic diseases such as lupus. We previously found that cells from patients with lupus show above-normal amounts of glycans. Moreover, blood from mice with lupus contains increased levels of the immune system proteins known as antibodies that target the glycans. Our new study will attempt to discover whether glycans from our cells and antibodies against them play a key role in lupus. We will determine the structure of glycans in the blood of patients with lupus and explain how they stimulate immune responses. To investigate potential new ways of diagnosing the disease, we will also determine which glycans make up the coating that is found on the surface of cells from patients with lupus and how are they different from healthy individuals. We also want to figure out which glycans the antibodies in patients’ blood target. Our studies may help researchers better understand glycans’ involvement in lupus and suggest potential new therapies for preventing these molecules from stimulating the immune system in the disease.

2017 Funded Grant

 

Roberto Caricchio, MD
Temple University

 

With his TIL grant, Dr. Roberto Caricchio is studying whether usually harmless, common bacterial infections, such as urinary tract infections, might be an environmental trigger of lupus onset and flares in genetically at-risk individuals. Normally, a bacterial infection sets off the immune system to make antibodies and take other actions to fight off the invading bacteria. Dr. Caricchio’s theory is that in people who are susceptible to lupus, those infections also cause the immune system to make antibodies that recognize and attack a person’s own body.

 

What this study means to people with lupus

Dr. Caricchio will look specifically at urinary tract infections (UTIs) in people with and without lupus. Some bacteria that cause UTIs produce a protein called “curli” that can bind to DNA and form a compound that triggers lupus in mouse models. Preliminary evidence shows that individuals with lupus have antibodies against this curli/DNA compound. Dr. Caricchio will investigate whether curli/DNA antibodies can predict lupus in at-risk people and if UTIs in people who have lupus create curli/DNA compounds in their blood that cause flares. This exciting research could open a new avenue of approaches to treat and even prevent lupus.

2017 Funded Grant

 

Laura Carrel, PhD
The Pennsylvania State University College of Medicine

 

Lupus affects nine times more women than men. One explanation for this phenomenon lies in the difference between women’s and men’s chromosomes, the long pieces of DNA within each cell that contain our genes lined up one after the other like recipes in a cookbook. Women have two X chromosomes, while men have one X and one Y chromosome. Dr. Laura Carrel is investigating how this difference in the number of X chromosomes might cause women to be more susceptible to lupus than men.

 

Normally, in a woman’s cells, the genes on one of her X chromosomes are active and those on the other are turned off or inactive. But Dr. Carrel has shown that in all women, about 10% of genes on the “inactive” X chromosome escape from the inactivation process and are actually active. She hypothesizes that the level of gene activity on the inactive chromosome might be even higher in women with lupus. To test this theory, Dr. Carrel will study the immune cells of women with and without lupus to find X chromosome genes that are more active in women with lupus.

 

What this study means to people with lupus

This research project will help us understand the biology of lupus and point to new targets for drug discovery.

2017 Funded Grant

 

Katherine Fitzgerald, PhD
University of Massachusetts Medical School

 

Lupus affects nine times more women than men. One explanation for this SAVI (STING-associated vasculopathy with onset in early infancy) is a disease caused by a mutation in the gene that makes a protein called STING. In patients with SAVI, the STING protein is locked in its “on” position, causing immune cells to be constantly active. These active immune cells create inflammation that damages tissues throughout the body in a manner that is similar in many respects to lupus. While lupus is caused by more complex genetic and environmental factors than SAVI, the STING pathway may also play a role in lupus. Dr. Katherine Fitzgerald is exploring how the mutant STING protein goes rogue to trigger the lupus-like symptoms in mice.

 

What this study means to people with lupus

By focusing on the simpler model system of a single-gene disease like SAVI, Dr. Fitzgerald will gain new information about the STING pathway that can be applied to develop new treatment approaches for SAVI and lupus patients.

2017 Funded Grant

 

Chandra Mohan, MD, PhD
University of Houston

 

Lupus nephritis (kidney disease) is one of the most serious complications of lupus. With the TIL grant support, Dr. Mohan will build on his existing discoveries to evaluate a potential new therapeutic target for lupus nephritis.  In comparing the levels of 1,100 proteins in the urine of lupus patients and healthy controls, Dr. Mohan already found several differences, and one in particular stood out. The protein ALCAM (activated leukocyte cell adhesion molecule) was consistently higher in those with lupus compared to the controls. ALCAM is a small molecule on the outside of T cells of the immune system that helps the T cells move through the tissues of the body, including the kidney.

 

What this study means to people with lupus:
Dr. Mohan will find out how ALCAM is involved in lupus nephritis and evaluate whether it is a good target for new drug development to prevent or treat the complication.

20127 Funded Grant

 

Peter A. Nigrovic, MD
Brigham and Women’s Hospital, Inc

 

Scientists have found more than 50 regions of DNA that contribute to lupus risk. At least 35 of these DNA regions regulate gene activity—they serve as magnets that attract proteins, which in turn, act as control switches that determine whether a gene is more or less active. Variations in gene activity influence a person’s biology—for example, whether they are more or less likely to develop a disease like lupus.  The TIL grant will enable Dr. Nigrovic to study each of these 35 DNA control centers to determine how they contribute to lupus risk.

 

Dr. Nigrovic will identify the proteins that interact with the DNA regions using state-of-the-art technologies. Once the control proteins are known, he will be able to build up a more complete picture of the genes and biological pathways that cause lupus.

 

What this study means to people with lupus

This line of research is expected to discover new targets for treatments to prevent or cure lupus.

2017 Funded Grant

 

Janos Peti-Peterdi, MD, PhD
Keck School of Medicine of University of Southern California

 

Dr. Janos Peti-Peterdi studies what goes wrong with the kidneys in people with lupus and how kidneys damaged by lupus can be repaired. He has developed a pioneering research technique, known as “intravital imaging,” to use a highly sensitive microscope to directly examine in fine detail the kidneys in an animal model of lupus. He will also test two potential treatments for lupus nephritis and observe whether they are effective at repairing the kidneys by regenerating damaged cells. Using the insights and data gained as a springboard, Dr. Peti-Peterdi will then focus his research on patients with lupus nephritis to find ways to help their kidneys heal.

 

What this study means to people with lupus

This research project promises to improve treatment of lupus nephritis for the benefit of all patients with this serious complication.

2017 Funded Grant

 

Betty Tsao, PhD
Medical University of South Carolina

 

Dr. Betty Tsao found a mutation in a specific gene, NCF1, that predicts increased risk for several autoimmune diseases, including lupus. The mutation causes a reduction in the amount of reactive oxygen species (ROS), small chemicals that contain oxygen and other elements that are formed as a normal byproduct of the body’s metabolism. Hydrogen peroxide is one example of an ROS. Interestingly, ROS are normally thought of as troublemakers in the body, causing stress and tissue damage that contribute to many diseases, as well as signs of aging. To understand why a reduction in ROS might lead to lupus, Dr. Tsao will create an animal model with the mutated NCF1 gene. This model will allow her to understand how reduced ROS affects immune system cell function.

 

What this study means to people with lupus

Ultimately, Dr. Tsao expects to find new targets in the NCF1/ROS pathway for drug development to prevent or treat lupus.

2016 Funded Grant

 

Rong Fan, PhD
Yale University
Immune system cells communicate with each other by releasing chemicals known as cytokines. Dr. Fan and his team have created a microchip that allows us to eavesdrop on immune cells by measuring what cytokines they are producing. They will use this microchip to analyze blood cells from lupus patients. They plan to profile a type of T cell that promotes the tissue destruction of lupus, determining which cytokines these cells release and how they respond to treatment.What this study means for people with lupusDr. Fan and his team developed a microchip that can monitor the biomolecules released by immune cells. They anticipate that the chip will reveal how one type of

T cell triggers tissue damage in lupus and provide clues about how to prevent it.

2016 Funded Grant

 

Roger Greenberg, MD, PhD
University of Pennsylvania

 

Dr. Greenberg and his colleagues have discovered that mice that lack a certain cluster of interacting proteins, known as BRISC, don’t develop lupus. Their previous research identified several molecules that block BRISC and might be able to quell lupus symptoms. They now plan to test whether these molecules are beneficial in mice that develop the disease. They will also fine-tune the molecules to make them more effective, with the hope that they will lead to new therapies for the disease.

 

What this study means for people with lupus

Dr. Greenberg has identified a new culprit in lupus, a group of interacting proteins. He and his team are developing molecules that will block these proteins, which could lead to new treatments for lupus.

2016 Funded Grant

 

Ming-Lin Liu, MD, PhD
University of Pennsylvania Health System

 

Lupus patients develop skin rashes in response to sunlight and other triggers. Immune cells called neutrophils promote these lesions by spewing out their DNA. Dr. Liu has discovered that a protein known as ROCK is crucial to this process. He and his team will now test whether blocking ROCK stops neutrophils from releasing their DNA, thereby reducing skin inflammation in mice that are prone to lupus. the results of their study could suggest new ways to reduce skin rashes in lupus patients.

 

What this study means for people with lupus

Skin rashes are common in lupus patients. Dr. Liu’s research will ask whether preventing certain immune cells from releasing their DNA curbs skin inflammation.

2016 Funded Grant

 

Laurence Morel, PhD
University of Florida College of Medicine

 

A specific type of T cell drives the tissue damage that occurs in lupus. These cells need more energy than normal cells, and that might be their Achilles heel. Dr. Morel has found that the numbers of these T cells in mice can be reduced with common diabetes treatments such as metformin that deprive the cells of the sugar they need to survive. Now, her team plans to test whether these drugs can be used as a lupus therapy that will eliminate the problematic T cells.

 

What this study means for people with lupus

Dr. Morel and her group wants to determine whether lupus can be treated through common diabetes treatments that are used to fight against T cells.

2016 Funded Grant

 

Kerstin Nündel, PhD
University of Massachusetts Medical School

 

In lupus, proteins in the immune system known as toll-like receptors help trigger the damaging effects of the disease. But one of the proteins, known as TLR9, is the black sheep of the toll-like receptor family—it reduces the severity of lupus symptoms. Dr. Nündel’s research suggests that TLR9 is helpful because it prevents immune cells known as B cells from moving into tissues where they can cause injury. She now wants to uncover how TLR controls B cell movements and identify an approach for treatment that can stop their migration.

 

What this study means for people with lupus

The immune system is the villain in lupus, but one immune system protein appears to protect patients’ cells. Dr. Nündel seeks to find out how and whether this insight can lead to a potential treatment.

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