Decoding Immune-Mediated Diseases

Novel Approaches for Therapeutic Insights

JDRF, Lupus Research Alliance and National Multiple Sclerosis Society have joined forces to identify common mechanisms of autoimmunity. This is the first time these three leading autoimmune disease organizations are jointly funding research projects looking at common underlying disease mechanisms.

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ABOUT THE GRANTS

JDRF International, the Lupus Research Alliance and the National Multiple Sclerosis Society joined forces to accelerate research and discovery in autoimmunity and are proud to announce the recipients of their first, joint Decoding Immune-Mediated Diseases – Novel Approaches for Therapeutic Insights grants. In its first year, the grant program will support the research of eight grant recipients from major academic centers around the world.

FULL GRANT DETAILS

Purpose

JDRF International, the Lupus Research Alliance, and the National Multiple Sclerosis Society, solicited grant proposals from investigators across autoimmune and other relevant fields to advance the understanding of autoimmunity and to obtain more specific insights into commonalities and differences of immune pathways that govern these disease processes.

The incomplete knowledge of immune networks, pathways, disease pathogenesis and heterogeneity across multiple autoimmune diseases remains a challenge towards achieving optimal therapies. This grant program invited innovative ideas that address needs across multiple autoimmune diseases in novel ways that may allow us to make faster progress together.

Objective

The overall objective of this program is to stimulate new research on common mechanisms of autoimmunity to generate new insights for novel therapeutic approaches.

Background

Autoimmune diseases are chronic disorders in which the immune system produces an inappropriate response against its own cells, tissues and/or organs that results in inflammation and damage. An incomplete knowledge of disease pathogenesis and heterogeneity among patients is very common in many autoimmune diseases, representing a real challenge that impacts the effectiveness of clinical trial design and the ability to predict whether a person will respond to a given treatment.

2021 AWARD RECIPIENTS

JDRF-Lupus Research Alliance Co-Funded Research Awards

Chris Cotsapas, Ph.D.

Associate Professor
Yale University

Identification of pathogenic pathways through genomic engineering to identify shared genetic effects on people with T1D, SLE, and MS

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.

Thomas Pieber, M.D.

University of Graz, Austria 

COMET common mechanisms in autoimmunity

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.

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

Assistant Professor Stanford University

3D and single-cell epigenome technologies for autoimmune disease

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.

Alexandra-Chloé Villani, Ph.D.

Assistant Professor Massachusetts General Hospital, Harvard Medical School​

Single-cell genomics dissection of common immune networks driving autoimmunity

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.

Julie Zikherman, M.D.

Associate Professor University of California, San Francisco

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

Professor, Neurology
UCSF Weill Institute for Neurosciences

NR4A family as markers and mediators of B cell tolerance across autoimmune diseases: From antigen discovery to treatment

Julie Zikherman, M.D., Samuel Pleasure, M.D., Ph.D., Michael Wilson, M.D., Judith Ashouri, M.D., Joseph Derisi, Ph.D. (co-investigators)
University of California, San Francisco
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.

JDRF-National MS Society Co-Funded Research Awards

Amit Bar-Or, M.D.

Professor University of Pennsylvania

Linking multiple disease compartments in T1D and multiple sclerosis

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.

Kevan Herold, M.D.

Professor
Yale University

Analysis of antigen specific T cells in response to immune therapies in MS and T1D

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.

Lupus Research Alliance-Funded Research Awards

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

Professor Stanford University

Dissecting the genetics and host interactions of EBV-related autoimmunity

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.

ABOUT AUTOIMMUNE DISEASES

Autoimmune diseases are chronic disorders in which the immune system produces an inappropriate response against its own cells, tissues and/or organs that results in inflammation and damage. Approximately 24 million Americans suffer from the more than 80 autoimmune diseases. Some autoimmune diseases target one area of the body; for instance, type 1 diabetes (T1D) affects the pancreas while multiple sclerosis damages the nervous system. In contrast, systemic lupus erythematosus can affect the entire body, attacking virtually any organ or tissue.

 

 

Insufficient knowledge of how these diseases progress as well as their heterogeneity, that is, how the disease manifests differently in people – is a common challenge among type 1 diabetes (T1D), lupus and multiple sclerosis that this grant program aims to overcome. The Common Mechanisms of Autoimmunity grants 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. The 2021 awardees are examining possible common mechanisms that could cause or contribute to the development of at least two of the three autoimmune diseases. Ultimately, the researchers hope to find novel biological targets and strategies for therapeutic development to treat the diseases

About the Partnering Organizations

JDRF’s mission is to accelerate life-changing breakthroughs to cure, prevent and treat T1D and its complications. To accomplish this, JDRF has invested more than $2.5 billion in research funding since our inception. We are an organization built on a grassroots model of people connecting in their local communities, collaborating regionally for efficiency and broader fundraising impact, and uniting on a national stage to pool resources, passion, and energy. We collaborate with academic institutions, policymakers, and corporate and industry partners to develop and deliver a pipeline of innovative therapies to people living with T1D. Our staff and volunteers throughout the United States and our five international affiliates are dedicated to advocacy, community engagement and our vision of a world without T1D. For more information, please visit jdrf.org or follow us on Twitter (@JDRF), Facebook (@myjdrf), and Instagram (@jdrfhq).

The Lupus Research Alliance is the largest non-governmental, non-profit funder of lupus research worldwide. The organization aims to transform treatment by funding the most innovative lupus research, fostering diverse scientific talent, and driving discovery toward better diagnostics, improved treatments and ultimately a cure for lupus. Because the Lupus Research Alliance’s Board of Directors fund all administrative and fundraising costs, 100% of all donations goes to support lupus research programs. Visit LupusResearch.org to learn more about lupus and the research Lupus Research Alliance is funding to find new treatments and a cure.

The National MS Society, founded in 1946, funds cutting-edge research, drives change through advocacy, and provides programs and services to help people affected by MS live their best lives. Connect to learn more and get involved: nationalMSsociety.org, Facebook, Twitter, Instagram, YouTube or 1-800-344-4867.

NEWS

JDRF, Lupus Research Alliance and National Multiple Sclerosis Society Join Forces to Decode Common Mechanisms of Autoimmune Diseases

First Joint Common Mechanisms Grants Announced

NEW YORK, NY, February 18, 2021 – JDRF International, the Lupus Research Alliance and the National Multiple Sclerosis Society joined forces to accelerate research and discovery in autoimmunity and are proud to announce the recipients of their first joint grants. Called Decoding Immune-Mediated Diseases – Novel Approaches for Therapeutic Insights, the new grant program will support the research of eight grant recipients from major academic centers around the world. This marks the first time these three organizations are jointly funding research projects looking at common underlying disease mechanisms.

 

Autoimmune and immune-mediated diseases are chronic disorders in which the immune system produces a harmful response against its own cells, tissues and/or organs that results in inflammation and organ damage. According to the NIH, some 24 million Americans suffer from the more than 80 autoimmune diseases. Some autoimmune diseases target one area of the body; for instance, type 1 diabetes (T1D) affects the pancreas while multiple sclerosis (MS) damages the nervous system. In contrast, systemic lupus erythematosus (SLE) can affect the entire body, attacking virtually any organ or tissue.

 

Insufficient knowledge of how these diseases progress, as well as their heterogeneity is a common challenge among T1D, lupus and MS—that this grant program aims to overcome.  The Decoding Immune-Mediated Diseases grants will provide researchers either up to $450,000 over two years or $225,000 over one year depending on the scope of the project. Each study will investigate the immune system’s role in the development of lupus, T1D and/or MS. The 2021 awardees are examining possible common mechanisms that could cause or contribute to the development of at least two of the three autoimmune diseases. Ultimately, the researchers hope to find novel biological targets and strategies for therapies to treat the diseases.

 

Visit DecodingAutoimmunity.org to learn about each of the following grantees and their projects:

 

  • Amit Bar-Or, M.D., University of Pennsylvania – Linking Multiple Disease Compartments in T1D and Multiple Sclerosis
  • Chris Cotsapas, Ph.D., Yale University – Identification of Pathogenic Pathways Through Genomic Engineering to Identify Shared Genetic Effects on People with T1, SLE, and MS
  • Kevan Herold, M.D., Yale University – Analysis of Antigen Specific T Cells in Response to Immune Therapies in MS and T1D
  • Thomas Pieber, M.D., University of Graz – COMET Common Mechanisms in Autoimmunity
  • William Robinson, M.D./Ph.D., Stanford University – Dissecting the Genetics and Host Interactions of EBV-Related Autoimmunity
  • Ansuman Satpathy, M.D./Ph.D., Stanford University – 3D and Single-Cell Epigenome Technologies for Autoimmune Disease
  • Alexandra-Chloé Villani, Ph.D., Massachusetts General Hospital/Harvard Medical School – Single-Cell Genomics Dissection of Common Immune Networks Driving Autoimmunity
  • Julie Zikherman, M.D., University of California, San Francisco – NR4A Family as Markers and Mediators of B Cell Tolerance Across Autoimmune Diseases: From Antigen Discovery to Treatment

 

Goals for this Autoimmune Partnership

 

“Understanding the commonalities between autoimmune diseases and how they affect the body can be the key to ultimately unlocking cures applicable to multiple communities,” said Sanjoy Dutta, Ph.D., JDRF Vice President of Research. “JDRF is excited to partner with both the Lupus Research Alliance and the National MS Society to support this research and transform the lives of millions affected by these autoimmune and immune-mediated diseases.”

 

Teodora Staeva, Ph.D., LRA Chief Scientific Officer, notes, “Because the initiation and progression of autoimmune diseases are still poorly understood and their cure has yet to be identified, we joined with JDRF and NMSS to support projects that could provide broad insights into autoimmune diseases and identify pathways distinctly affected in each specific disease.” She adds, “Decoding the mechanisms common to these three serious disorders of the immune system will help scientists to not only develop therapeutic targets, but also to identify which patients can most benefit from them.”

 

“This partnership creates the opportunity to increase the pool of investigators working across autoimmune disease areas, exploring shared environmental and genetic risk factors and using comparative approaches to provide insights on the most promising pathways to target each disease. We hope this research will lead to new strategies to regulate the immune system,” says Mark Allegretta, Ph.D., Vice President of Research at the National MS Society.

 

Visit DecodingAutoimmunity.org for more information.

 

 

About JDRF International
JDRF’s mission is to accelerate life-changing breakthroughs to cure, prevent and treat T1D and its complications. To accomplish this, JDRF has invested more than $2.5 billion in research funding since our inception. We are an organization built on a grassroots model of people connecting in their local communities, collaborating regionally for efficiency and broader fundraising impact, and uniting on a national stage to pool resources, passion, and energy. We collaborate with academic institutions, policymakers, and corporate and industry partners to develop and deliver a pipeline of innovative therapies to people living with T1D. Our staff and volunteers throughout the United States and our five international affiliates are dedicated to advocacy, community engagement and our vision of a world without T1D. For more information, please visit jdrf.org or follow us on Twitter (@JDRF), Facebook (@myjdrf), and Instagram (@jdrfhq).

 

 

About the Lupus Research Alliance
The Lupus Research Alliance is the largest non-governmental, non-profit funder of lupus research worldwide. The organization aims to transform treatment by funding the most innovative lupus research, fostering diverse scientific talent, and driving discovery toward better diagnostics, improved treatments and ultimately a cure for lupus. Because the Lupus Research Alliance’s Board of Directors fund all administrative and fundraising costs, 100% of all donations goes to support lupus research programs. Visit LupusResearch.org to learn more about lupus and the research LRA is funding to find new treatments and a cure.

 

 

About the National MS Society
The National MS Society, founded in 1946, funds cutting-edge research, drives change through advocacy, and provides programs and services to help people affected by MS live their best lives. Connect to learn more and get involved: nationalMSsociety.org, Facebook, Twitter, Instagram, YouTube or 1-800-344-4867.

 

 

Media Contacts:

 

Ayana Young, JDRF
AYoung@jdrf.org

 

Margy Meislin, Lupus Research Alliance
MMeislin@lupusresearch.org

 

Daphne Mack, National MS Society
Daphne.Mack@nmss.org