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2017 Novel Research Grants

Lupus Research Alliance Commits over $4 Million for Studies to Improve Lupus Treatment

The Lupus Research Alliance announces the Novel Research Grant Class of 2017.  The Lupus Research Alliance Novel Research Grants, the proven platform for innovation, make discovery and scientific progress possible.

This year’s grantees push science out in front and ahead of the curve to deliver 10 innovative approaches seeking results that can transform the lives of people with lupus.

“Standing on a 16-year foundation of documented success, the Novel Research Grants bring new insight and untried directions to the complexities of lupus,” said Lupus Research Alliance Co-CEO Margaret Dowd. “The program works because we create a space where scientists are encouraged to explore at the frontiers of current knowledge and to imagine without limits.”


Mridu Acharya, Ph.D.

Benaroya Research Institute at Virginia Mason, Seattle, WA << view more >>
AUTOPHAGY COMPONENTS AND B CELL ACTIVATION DURING SLE

The B cells of lupus patients are hyperactive, causing inflammation and damage to tissues. By studying mice, Dr. Acharya and her team have discovered a new molecular control switch for these cells. In their new study, they want to find out more about how this control switch works in human B cells and why it doesn’t function properly when people develop lupus. Some patients carry varying versions of the switch proteins, and they also want to investigate how these genetic differences affect whether someone gets lupus. Better understanding of the control switch will help efforts to develop new treatments that readjust this molecular switch in patients with lupus.

What this means for people with lupus: Dr. Acharya’s team has found a new pathway in lupus, having identified proteins that normally work together to prevent B cells, a type of immune cell that releases disease-fighting molecules, from targeting patients’ cells. Working with human B Cells, they will investigate why these proteins fail to put on the brakes in lupus and potential new treatments to get them working properly again.

Natalia Giltiay, Ph.D.

University of Washington, Seattle, WA<< view more >>
ANTI-BDCA2-TARGETED THERAPY FOR SLE

Our cells store their DNA by wrapping it around proteins called histones. People with lupus show abnormal immune system responses against their own DNA and against histones. Dr. Giltiay thinks that histones are a little like the substances that cause allergies—they stimulate the immune system inappropriately, but controlled exposure to them may reduce this reaction. Her team’s strategy to prevent these “allergic” reactions involves delivering small bits of self-proteins to key immune cells known as dendritic cells, which control the responses of other immune cells. They have developed molecules known as antibodies that home in on dendritic cells and bring the histone fragments along with them. They hypothesize that exposing dendritic cells to the fragments will curb the immune system reaction against histones, and our new study will test this approach in mice that are prone to lupus. Their goal is to apply their work to the development of a new therapy for lupus patients.

What this means for people with lupus: Dr. Giltiay plans to teach the immune system to tolerate the body’s own cells in much the same way that allergy shots curb abnormal reactions to allergens. This novel approach to inducing immune system “tolerance” has never been applied to lupus before and may lead to a new effective treatment.

Andrea Knight, M.D.

The Children's Hospital of Philadelphia, Philadelphia, PA<< view more >>
MULTI-LEVEL BIOMARKERS FOR PSYCHIATRIC DISORDERS IN PEDIATRIC LUPUS

Up to 50% of young people with lupus have neuropsychiatric disorders, but many of these patients don’t receive the treatment they need. Dr. Knight’s study will ask whether a variety of tests, including brain scans with magnetic resonance imaging (MRI) and analysis of proteins in blood samples, can help identify which patients have these disorders due to lupus. She and her team anticipate that the results of the study will lead to early detection and targeted treatment of neuropsychiatric disorders in young people with lupus.

What this means for people with lupus: Young people with lupus often have neuropsychiatric disorders like depression or anxiety, which may be caused by brain inflammation. Dr. Knight’s team is developing a new biomarker to better detect and diagnose neuropsychiatric disorders like depression and anxiety that are common in pediatric patients so they can receive treatment and get relief sooner.

Vipin Kumar, Ph.D.

University of California, San Diego, San Diego, CA << view more >>
TARGETING TYPE II NKT CELLS FOR A NOVEL THERAPEUTIC IN LUPUS

Dr. Kumar and his colleagues have found that certain immune cells accumulate in the kidneys of mice with a lupus-like disease. Their research has shown that molecules structurally related to sulfatide that stimulate these cells can prevent kidney disease in animal models of lupus. One such analog has been used for the treatment for the tropical disease leishmaniasis. In their new study they want to determine whether this lipid analog can reduce kidney damage in lupus-prone mice. If successful, the results could lead to clinical trials to examine whether the self-lipid analogs can also serve as a treatment for kidney disease in lupus patients. .

What this means for people with lupus: Some immune cells drive renal damage in lupus, but others serve a protective role. Dr. Kumar’s team have identified a specific population of protective cells that can be stimulated by a drug currently used for treating tropical parasitosis, and we are testing a novel hypothesis backed by our preliminary data. They will explore a drug used to fight tropical parasites as a potential oral medication to prevent and treat kidney damage in lupus.

Shaun Jackson M.D., Ph.D.

Seattle Children's Hospital, Seattle, WA<< view more >>
BCELL-INTRINSIC CYTOKINE REG OF SPONTANEOUS GERMINAL CTR FORMATION IN SLE

B cells usually protect us from bacteria and viruses, but in lupus they release proteins, known as antibodies, that target patients’ own cells. Researchers don’t know which immune system molecules spur B cells to start making these destructive antibodies. Dr. Jackson’s study will use mice to test whether specific immune system molecules, called cytokines, activate B cells to promote production of these antibodies. By identifying the specific signals that trigger B cells to attack patients’ own cells, they hope to provide clues that will allow researchers to develop new, targeted lupus treatments.

What this means for people with lupus: In lupus, immune cells known as B cells release proteins that damage patients’ own tissues. Dr. Jackson is zeroing in on two recently identified molecules that may act as signals to promote immune attacks. Identifying the specific signals responsible for activating B cells and producing dangerous autoantibodies will inform development of potential targeted lupus treatments.

Christian Lood, Ph.D.

University of Washington, Seattle, WA<< view more >>
IMPAIRED MITOCHONDRIAL CLEARANCE IN SYSTEMIC LUPUS ERYTHEMATOSUS

The energy our cells need comes from structures known as mitochondria that serve as power plants. Dr. Lood recently found that some immune cells throw out their mitochondria, which trigger inflammation and promote development of disease. In the current study his team proposes to investigate how the body normally disposes of the released mitochondria so that they don’t cause inflammation and find out if those clean-up mechanisms don’t work well in lupus patients. Those results may provide new opportunities for developing lupus therapies, as well as identify novel biomarkers to monitor, and potentially predict, development of disease.

What this means for people with lupus: Dr. Lood and his team have discovered a new cause for the out-of-control inflammation of lupus. They are exploring a new treatment approach by examining whether people with lupus do not properly remove excess energy-producing structures, known as mitochondria, thus sparking inflammation. This highly novel project is likely to lead to new targets for therapy and new biomarkers for evaluating disease progression and response to treatment.

Anthony Rongvaux, Ph.D.

Fred Hutchinson Cancer Research Center, Seattle, WA<< view more >>
MITOCHONDRIA, CASPASES AND TYPE I INTERFERONS IN AUTOIMMUNITY

The immune system molecules known as interferons protect us from infections, but they also spur tissue damage in lupus. Dr. Rongvaux and his team have discovered a previously unknown mechanism by which interferons may cause or worsen lupus. Using state-of-the-art technologies, they are investigating how some proteins, known as caspases, block this novel interferon mechanism. They also will test molecules that stimulate caspases, some of which are under development as potential treatments for diseases such as cancer, to determine if they reverse lupus symptoms in mice.

What this means for people with lupus: Dr. Rongvaux’s work is using state-of-the-art technology to study a newly discovered process that may cause or worsen lupus and whether molecules involved in this process are potential targets to validate and advance new treatments that may reverse symptoms.

Guo-Ping Shi, D.Sc..

Brigham and Women's Hospital, Boston, MA << view more >>
CATHEPSIN S INHIBITOR-MODIFIED TREG CELLS MITIGATE MURINE SLE

Regulatory T cells serve as the immune system’s dimmer switch, turning down attacks by immune cells. One factor causing regulatory T cells to fail in lupus patients might be the protein cathepsin S. This protein switches on another protein, known as toll-like receptor 7, that curbs the body’s production of regulatory T cells and prevents them from inhibiting the immune system. Dr. Shi’s study will test whether blocking cathepsin S reduces lupus symptoms in mice by increasing the lifespan of regulatory T cells and boosting their ability to rein in the immune system. If this study is successful, it might be possible to block cathepsin S in regulatory T cells and then use the cells to treat lupus patients.

What this means for people with lupus: Dr. Shi and his team are investigating the enzyme Cathepsin S in controlling regulatory T cells, which rein in the immune system, from malfunctioning and to restore their ability to control other defensive cells. They are testing in human cells an approach that might keep these T cells working and thus could furnish a novel way to treat lupus.

John Zhang, D.V.M., Ph.D.

Medical University of South Carolina, Charleston, SC << view more >>
A NOVEL APPROACH FOR TREATING LUPUS BY INHIBITING FLI1 TRANSCRIPTION FACTOR

Lupus patients with active disease produce higher-than-normal amounts of the protein Fli-1 in their immune cells. The more of the protein they make, the worse their symptoms are. Dr. Zhang and colleagues have found that the drug topotecan, a therapy for ovarian cancer and other types of cancers, curbs production of Fli-1 and reduces the signs of inflammation in cells. They will test whether the drug has beneficial effects in lupus-prone mice. Their results will help demonstrate whether the drug has potential as a lupus treatment in patients.

What this means for people with lupus: Researchers have identified a protein, Fli-1, in immune cells that worsens lupus symptoms. Dr. Zhang and his team are confirming their earlier data, now testing the cancer drug topotecan, which blocks this protein, in human cells. If the drug reduces symptoms in the animals, it can be tested as a therapy in lupus patients.

Zhiqiang Zhang, Ph.D.

The Methodist Hospital Research Institute, Houston, TX << view more >>
OXIDIZED MITOCHONDRIAL DNA EMPLOYS APEX1 IN NEUTROPHILS TO CONTROL LUPUS


The immune system keeps watch for viral DNA that signals we have an infection. In lupus, immune cells identify DNA from patients’ cells as dangerous. Some of the DNA released by their cells comes from mitochondria, the structures that provide energy for our cells. Dr. Zhang and his team have identified several proteins that may recognize this DNA, including one known as APEX1. In their new study, they will test whether APEX1 detects mitochondrial DNA and spurs the immune system attacks. Their results could provide important information for the development of safer and more effective approaches for the prevention and control of lupus without unwanted side effects.

What this means for people with lupus: The immune system mistakenly attacks lupus patients’ own DNA. Dr. Zhang’s study asks whether the protein he and his team just discovered, APEX1, is responsible for sounding a distress call that stimulates our defensive cells. This work could allow researchers to develop new ways to prevent this false alarm and reduce lupus symptoms.

Learn more about the many grants funded by the Lupus Research Alliance to advance scientific discovery in lupus.


1.5 million

people in the U.S. have Lupus.

172 million

dollars committed to lupus research by the Lupus Research Alliance.


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