The LRA-BMS Accelerator Award ($300,000 for 2 years) is a collaborative project with sponsoring partner Bristol Myers Squibb supporting research on understanding human lupus heterogeneity and identifying novel biomarkers.
New Drug Targets for Lupus Through Mechanistic Modeling of Multi-OMICs Data
2020 Funded Grant
Marta Alarcon-Riquelme, MD, PhD
Fundación Pública Andaluza Progreso y Salud
Much previous research has identified several genetic risk factors for developing lupus; but has focused on studying very diverse patient populations. Some patients may have systemic lupus, while others only have cutaneous (skin) lupus or lupus nephritis (inflammation of the kidneys). While this allows scientists to identify genetic factors common across lupus types, there are likely important risk factors unique to each type. Even within a specific type of lupus, significant differences in the immune response can occur. Dr. Riquelme’s research has been investigating the differences present in systemic lupus and found that patients can be differentiated into three groups based on their immune response. However, the reasons for these differences are not clear since the genes associated with these differences are not known. In her study, Dr. Riquelme will identify these genes and determine what function they play in altering the immune response during lupus. In addition, she will observe whether these genes are associated with changes in the treatment success for each group of patients.
What this study means for people with lupus
Dr. Riquelme’s study will help determine which genes lead to the differences in immune response observed in different lupus patients. Her research may also help determine which are the best therapies for specific groups of people with lupus.
Biomarker identification in SLE identified via microbiome-host interactions
2020 Funded Grant
Ilana Brito, PhD
Cornell University
Lupus causes an immune response targeted against normal human cells. However, it is not known what triggers this response to start. Recently, Dr. Brito devised a method to determine how proteins produced by bacteria found in individuals’ guts, impact the normal function of immune cells. Although it is known that the microbiomes of patients with lupus have notable differences than healthy patients, now, with much higher resolution, Dr. Brito’s team will determine the specific effects of these microbiome differences. Her team will test individual gut bacteria-derived proteins for their ability to change immune cell function and look for these proteins in the blood of patients with lupus.
What this study means for people with lupus
This study will help identify new markers of lupus that could function as targets for development of potential treatments. If these markers are found in the blood of lupus patients, they may also be useful for diagnosing lupus.
Pathogenesis of Chronic Cutaneous Lupus Erythematosus
2020 Funded Grant
Joseph Craft, PhD
Yale University
In some people with systemic lupus erythematosus (SLE, lupus), immune cells from the blood enter the skin and inappropriately cause repeated injury, which is known as chronic cutaneous lupus erythematosus (CCLE). Dr. Craft will study how these cells cause damage using a combination of cutting-edge techniques to study both the damage-causing immune cells and the injured skin cells. The study will reveal new understanding of what causes chronic cutaneous lupus so new therapies for people living with this debilitating condition can be developed.
What this study means for people with lupus
This study will reveal more effective therapy approaches for people living with damage to the skin caused by lupus.
Epigenome profiling in human SLE
2020 Funded Grant
Patrick Gaffney, MD
Oklahoma Medical Research Foundation
For many years, it has been recognized that people of African American race/ethnicity are at higher risk of developing systemic lupus than other racial/ethnic groups. African American patients with lupus are also more likely to have serious organ-specific forms of lupus such as lupus nephritis (lupus damaging the kidneys) and cutaneous lupus (damaging the skin). However, the reasons for the differences in risk are still unknown. This makes it especially important to understand the genetic risk factors for lupus in this population, and to develop treatments targeted to these risk factors. Dr. Gaffney’s study focuses on identifying the genetic risk factors of lupus in African Americans. Using samples taken from lupus patients and healthy African American donors, he will be able to determine which factors best predict lupus in this population. After completing this analysis, he aims to compare these genes to data from European Americans to determine which risk factors are unique to African Americans.
What this study means for people with lupus
This study will help uncover how race and ethnicity are linked to the development of lupus and to identify new treatment targets.
Dissecting Molecular Heterogeneity of SLE Patient Treatment Response
2020 Funded Grant
Joel Guthridge, PhD
Oklahoma Medical Research Foundation
Although there are a number of lupus treatments available, there is no way to predict which drugs will work for a specific patient without relying on trial and error. One lupus drug called abatacept works by impairing the function of a type of immune cells known as T cells. In people with lupus, T cells cause inflammation that harms healthy human cells and results in symptoms. By interfering with T cells, abatacept lowers the level of inflammation and alleviates symptoms. Even though abatacept works for many lupus patients, for unknown reasons this drug does not help everyone. Dr. Guthridge’s study is using emerging technology to compare the blood samples from patients whose lupus does respond to treatment with that of lupus patients who do not improve with abatacept therapy. By comparing the immune cells in each sample, he aims to determine what is different about the immune response in patients who respond to treatment compared to those who don’t.
What this study means for people with lupus
This study will identify differences in the immune system that can predict which patients are likely to benefit from treatment with abatacept.
Longitudinal systemic and organ-specific heterogeneity in lupus
2020 Funded Grant
J. Michelle Kahlenberg, MD, PhD
University of Michigan
Most research on lupus does not address whether the immune response in people with systemic lupus is different from the immune response in those with organ-specific lupus such as lupus nephritis (inflammation of the kidney) and cutaneous (skin) lupus. Since skin samples can be obtained without invasive surgery, cutaneous lupus is well suited for research. Dr. Kahlenberg’s study will compare the immune response in systemic lupus to cutaneous lupus. Using blood and skin samples from lupus patients, her laboratory is measuring differences in the immune cells over the course of treatment. The immune response in the blood and skin will be compared between patients with systemic or cutaneous lupus. This will help Dr. Kahlenberg determine what is both similar and different between these groups of patients. She will also measure the immune response to treatment within each patient over time. This will allow Dr. Kahlenberg to learn whether certain immune cells can predict when patients will best respond to treatment.
What this study means for people with lupus
The information obtained from this study will help researchers better understand the difference in immune response between systemic and cutaneous lupus. Identifying these differences is important for the development of more specialized treatments. Dr. Kahlenberg’s study will also help healthcare providers better predict which drugs will benefit each lupus patient.
Developing a Novel Outcome Approach for Clinical Trials
2020 Funded Grant
Kenneth Carekin Kalunian, MD
University of California, San Diego
Clinical trials are an important part of testing potential treatments before they can be approved by the U.S. Food and Drug Administration for use by patients. While many clinical trials have been performed for lupus treatments, results of different studies are often difficult to compare due to differences in the criteria used to define treatment success. While these differences may seem minor, they can have a strong impact on which drugs are chosen to go on for further development to benefit patients, and which are abandoned. Dr. Kalunian’s study aims to improve the criteria used to define treatment success in clinical trials for lupus therapies. Dr. Kalunian will identify the criteria that is easiest and most helpful in determining if treatments have been successful. He intends to use these insights to create a tool that combines the most useful criteria.
What this study means for people with lupus
With his grant, Dr. Kalunian will develop a comprehensive tool to help researchers better understand and evaluate the effectiveness of potential lupus therapies in clinical trials.
Virtual Transcriptome and Proteome in Lupus Pathogenesis and Heterogeneity
2020 Funded Grant
Vivian K Kawai, MD
Vanderbilt University Medical Center
Many genetic risk factors for lupus have been identified, but it isn’t clear how or why many of them are linked to the disease. Some lupus risk factors may be responsible for specific clinical symptoms, while others are associated with the severity of disease. Some genes may not actually be linked to the development of lupus at all, or to its severity. Environmental conditions such as medications and illness may cause normally neutral genes to play a harmful role. These environmental factors make it difficult to determine what effects are caused by the genes compared to the environment. Dr. Kawai’s research focuses on developing methods to isolate the genetic components of disease from those exerted by environmental factors. In this study, she will compare the genes of patients with lupus to healthy controls to identify gene changes that are unique to lupus patients. In addition, she will identify whether these differences in genes lead to important differences in the amount of proteins produced by the body. Dr. Kawai’s study will also determine which genes are associated with lupus severity.
What this study means for people with lupus
Dr. Kawai’s study will help researchers better understand the genetic risk factors for lupus as well as its severity. Her findings may also help doctors predict which lupus patients are likely to develop more severe lupus over time.
Urinomics as a Guide to the Renal Immune Landscape in SLE
2020 Funded Grant
Chandra Mohan, MD, PhD
University of Houston
The most common organ-specific form of lupus is known as lupus nephritis, which means inflammation of the kidneys. Many patients with lupus nephritis must undergo surgical kidney biopsies to monitor their condition. Since these procedures are invasive and not without risk, other methods to monitor kidney function are needed. Urine tests are already done to monitor some aspects of lupus nephritis treatment, and would be an ideal replacement for kidney biopsies. Dr. Mohan’s research has already identified several promising markers in the urine of lupus nephritis patients that seem to be associated with clinically active disease. In this study, Dr. Mohan will be comparing how urine testing for these markers compares to testing kidney biopsies in detecting active lupus nephritis and monitoring treatment response.
What this study means for people with lupus
If urine screening is successful, this less invasive method of patient monitoring may remove the need for kidney biopsies to diagnose and monitor lupus nephritis.
Immunologic Mechanisms for Heterogeneity of Cutaneous Lupus Erythematosus
2020 Funded Grant
Victoria Werth, MD
University of Pennsylvania
Antimalarial drugs such as hydroxychloroquine are commonly used to treat cutaneous (skin) lupus and prevent disease flare-ups. While they help many people with cutaneous lupus, some do not respond to treatment. Since it takes several months for antimalarial drugs to begin controlling cutaneous lupus, this leads to prolonged suffering for patients who must wait to then find out treatment isn’t working and need to switch to a different drug. To predict which patients are likely to respond to this drug before starting treatment, Dr. Werth is studying skin lesions from lupus patients given hydroxychloroquine, hydroxychloroquine and quinacrine, and those who don’t respond to antimalarials. Dr. Werth’s study will identify key immune cells that correlate with successful treatment.
What this study means for people with lupus
This study will allow clinicians to predict which patients are likely to respond to treatment with hydroxychloroquine or combination antimalarials before starting on the drug.
