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Common Mechanisms in Autoimmunity

The Common Mechanisms of Autoimmunity grants (up to $450,000 over two years or $225,000 over one year) will provide researchers up to $200,000 a year for up to two years to investigate the immune system’s role in the development of lupus, type 1 diabetes, and/or multiple sclerosis. Visit decodingautoimmunity.org to learn more about this grant.

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2020 Funded Grant

 

Chris Cotsapas, Ph.D.

 

Associate Professor
Yale University
Dr. Cotsapas has developed a set of diagnostic tools to compare genetic information from different diseases and identify the regions in the genome (DNA) associated with the disease risks. He will use genome engineering—a way to make changes in the DNA—to determine the effect of a specific alteration of the DNA on the function of immune cells and uncover the biological basis for risk shared across autoimmune diseases, and find specific pathways that can be targeted for drug development. Type 1 diabetes, systemic lupus erythematosus, and multiple sclerosis share some—but not all—genetic risk factors, pointing to shared cellular mechanisms that cause disease. Dr. Cotsapas has developed a set of statistical tools to compare genetic information from these autoimmune diseases and identify the specific regions in the genome (DNA) affected across these diseases. He will use genome engineering—a way to make changes in the DNA—to create those exact changes in normal immune cells, to see how they affect the function of those cells. In this way, he will uncover the biological basis for risk shared across type 1 diabetes, lupus, and multiple sclerosis, and find specific pathways that can be targeted for drug development.

2020 Funded Grant

 

Thomas Pieber, M.D.

University of Graz, Austria

 

Dr. Pieber and his team will apply highly sophisticated computerized machine-learning approaches on existing data from people with type 1 diabetes, systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis and healthy volunteers, to identify the changes in different immune cells that are shared between the autoimmune diseases or unique to each. (Machine learning are computer programs that improve automatically through experience, which can help researchers find patterns from large-scale datasets.) This will generate a deeper understanding of commonalities and differences of immunological patterns in type 1 diabetes, lupus, multiple sclerosis, and rheumatoid arthritis, and will identify important pathways in immune cells that can then be tested for potential therapies.

2020 Funded Grant

 

Ansuman Satpathy, M.D., Ph.D.

Assistant Professor
Stanford University

 

Dr. Satpathy will use the cutting-edge technology that can obtain genomic information on the status of each gene in an individual cell, allowing the detection of molecular differences that could be obscured in a pool of cells. Applying this approach on immune cells from healthy individuals and people with autoimmune diseases—including type 1 diabetes, systemic lupus erythematous, and multiple sclerosis—he aims to identify the genes and pathways associated uniquely with each disease and shared between the diseases. He anticipates that these studies will lead to a single-cell atlas of autoimmune disease-associated genetic factors, leading to novel insights into the shared and disease-specific mechanisms governing each disease and propose new strategies for therapeutic intervention.

2020 Funded Grant

 

Alexandra-Chloé Villani, Ph.D.

Assistant Professor
Massachusetts General Hospital, Harvard Medical School​
Dr. Villani will be leveraging the power of new state-of-the-art single-cell genomics and immunology technologies to identify the type and the characteristic of each single cell from blood and tissue samples from healthy individuals and people with lupus, multiple sclerosis, rheumatoid arthritis, and type 1 diabetes, as well as cancer patients treated with immunotherapy and, later, diagnosed with immune-related adverse events that mimic clinical features of autoimmune disease presentations. By comparing the composition of cell types and the states of the cells between tissues and blood specimens obtained from different diseases, she will be able to identify shared biological processes and pathways that could be targeted for therapeutic potential.

2020 Funded Grant
Julie Zikherman, M.D.
Associate Professor
University of California, San Francisco

Samuel Pleasure, M.D., Ph.D.

Professor, Neurology
UCSF Weill Institute for Neurosciences
When activated by infection or vaccination, B cells can produce antibodies against foreign invaders. “Self-reactive” B cells can produce autoantibodies, which can mistakenly tag cells in the body as foreign, thereby triggering the immune system to attack. Dr. Zikherman and colleagues previously showed that a small group of molecules—members of the NR4A family—are expressed at high levels in self-reactive B cells. She and her team of co-investigators will take advantage of high NR4A expression in self-reactive B cells to identify such cells in people with type 1 diabetes, multiple sclerosis, and systemic lupus erythematous. The investigative team will couple this with a novel high-throughput phage-display platform to screen samples from people in order to identify specific autoantigens and autoantibodies. The goal of this work is to define targets and genetic programs that guide disease-causing B cells to promote autoimmunity, to identify new disease biomarkers, and to develop new therapeutic approaches to eliminate such B cells selectively.

2020 Funded Grant

 

Amit Bar-Or, M.D.

Professor
University of Pennsylvania

To date, no studies have been able to ‘connect the dots’ between more and less accessible immune compartments in type 1 diabetes and multiple sclerosis, mainly because of limited access to the more disease-relevant immune cells. In particular, it remains unclear how immune cells in the blood relate to those that are associated with the pancreas in T1D, or the central nervous system in multiple sclerosis. Dr. Bar-Or’s study will elucidate immune cell profiles in three distinct anatomic compartments: target organ-associated immune cells, tissue-draining (lymphatic) immune cells, and circulating blood. Through this, Dr. Bar-Or will learn not only about previously unexplored roles and relationships of immune cells in type 1 diabetes and multiple sclerosis, but also of similarities and differences that may exist between people with these two immune-mediated conditions. Ultimately, he hopes that he will identify measurements in the blood that better reflect what is actually happening in the tissue being injured, so he can more effectively and safely target them therapeutically and monitor response to therapies.

2020 Funded Grant

 

Kevan Herold, M.D.

Professor
Yale University
In identical twins, one of whom has type 1 diabetes and the other who doesn’t, for example, both may have immune cells that are activated for beta cell molecules, but the immune cells in the unaffected sibling do not cause disease. Why? Dr. Herold will study the immune cells that have been activated for target-organ molecules, in type 1 diabetes and multiple sclerosis, to identify features that account for their ability to cause autoimmunity. In addition, anti-CD20 antibodies—against specific types of immune cells called B cells—have been used to treat both diseases, but the ways in which they change immune cells called T cells is not known. Dr. Herold will study how successful immune therapy changes these cells. He anticipates that it will lead to the identification of markers that can be used to track the diseases’ development, as well as suggesting combination therapies that may be used to extend the effectiveness of immune therapy.

 

2020 Funded Grant

 

William Robinson, M.D., Ph.D.

Professor
Stanford University
Epstein-Barr virus (EBV) is thought to be a possible trigger for many autoimmune diseases, in particular multiple sclerosis and systemic lupus erythematosus, but how EBV might promote these diseases is poorly understood. Dr. Robinson’s study will apply next-generation technologies to determine if and how EBV plays a central role in facilitating autoimmunity. He will investigate these key questions: Does EBV infection drive immune cell autoimmunity? How does EBV transform immune cells to promote autoimmunity in these diseases? Are there specific EBV strains that cause multiple sclerosis and/or lupus? Success of the study will identify the mechanisms by which EBV promotes multiple sclerosis and lupus and could lead to the development of next-generation therapies for these diseases.

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