UC San Francisco scientists have formed a research alliance with pharmaceutical firm Eli Lilly and Company aimed at better understanding autoimmune diseases and fostering the development of new therapies. Based on the innovative Immunoprofiler model launched at UCSF in 2015, the new initiative, called AutoImmunoprofiler, inherits the most successful aspects of its predecessor and adapts them to the study of autoimmunity.
Autoimmune diseases such as lupus, inflammatory bowel disease, and type 1 diabetes occur when the immune system attacks the body’s own tissues. While there are some therapies to treat symptoms of these conditions, the underlying causes are largely unknown.
“What we have learned through the first Immunoprofiler consortium’s work on cancer is that the immune system likely has a limited number of tricks,” said AutoImmunoprofiler co-leader Matthew “Max” Krummel, PhD, professor of pathology. “If we can find all the key circuits that control the immune system, we can understand how it will behave in response to different inflammatory diseases.”
With foundational funding from Lilly, AutoImmunoprofiler launches with the goal of bringing up to four additional pharmaceutical companies into the consortium. Like Lilly, all these partner investors will have access to research data generated from biological samples through standardized procedures developed in the high-tech CoLabs facilities at UCSF. David Erle, MD, professor of medicine and director of the UCSF Colabs, said the hope is that this communal research environment will result in new breakthroughs in understanding the autoimmune disease.
In addition to Krummel and Erle, UCSF scientific leaders of the AutoImmunoprofiler project include Jeroen Roose, PhD, professor of anatomy; Lindsey Criswell, MD, MPH, vice chancellor for research and Jean S. Engleman Distinguished Professor of Rheumatology; Jimmie Ye, PhD, associate professor of medicine; and Vincent Chan, PhD, assistant professor of microbiology and immunology.
The clinical programs for the first phase of the Autoimmunoprofiler consortium are led by Mark Anderson, MD, PhD, professor in the UCSF Diabetes Center (Type 1 diabetes); Maria Dall’Era, MD, professor of medicine (systemic lupus erythematosus); Caroline Shiboski, DDS, MPH, PhD, the Leland A. and Gladys K. Barber Distinguished Professor in Dentistry and chair of the Department of Orofacial Sciences in the UCSF School of Dentistry (Sjögren’s syndrome); Michael Kattah, MD, PhD, assistant professor of medicine (ulcerative colitis and Crohn’s disease); Andrew Gross, MD, professor of medicine; and Sarah French, MD, professor of medicine (scleroderma).
“UCSF has a collaborative group of investigators who are innovating new genomics and single-cell technologies, as well as clinicians who have extensive expertise in specific autoimmune diseases,” said Ye. “This combination creates a unique opportunity to study autoimmune diseases at unprecedented precision and resolution.
The team will collect tissue and blood samples from patients with various forms of autoimmune disease and analyze these samples using techniques like single-cell RNA sequencing. With the help of the Organoid D2B unit, they’ll also create a tissue bank of organoids – 3D, tissue-like balls of cells grown in the lab from samples donated by patients with inflammatory bowel disease. One of the key goals of these analyses will be to identify what the team calls “autoimmune archetypes.”
Immune system archetypes, Krummel said, offer a way to classify the behavior of the immune system and how it reacts to disease. One of the key findings of the original Immunoprofiler initiative was that despite all the genetic diversity in the population, there are a limited number of ways the immune system reacts to cancer. The same is likely true for autoimmune disease, and AutoImmunoprofiler aims to identify similar archetypes for these diseases.
“It’s kind of like asking how many different kinds of people there are – it depends on how you look at it,” said Krummel. “In terms of the way the immune system responds to cancer we see about a dozen archetypes and we expect to find a similar number for autoimmune disease.”
Identifying autoimmune archetypes will help the researchers understand the central operating mechanisms underlying autoimmune disease, potentially revealing hidden connections between seemingly unrelated illnesses. Understanding these connections may help speed the development of new treatments and identify existing drugs that may have the potential to treat several different autoimmune disorders.
The original Immunoprofiler initiative produced a similar breakthrough in understanding the importance of immune system cells known as dendritic cells. The data-sharing model of the consortium allowed researchers to discover that the behavior of dendritic cells largely determines the effectiveness of T cell therapies against cancer.
The discovery of the importance of dendritic cells in cancer treatments is an example of the research success of the Immunoprofiler program, but Krummel and Roose believe that the true legacy of that program is in the model itself – what they call a “pre-competitive space.” This model provides several unique advantages for pharmaceutical company partners and academic scientists alike.
“This unique public–private structure fosters a collaborative culture and allows us to tackle important biological questions. We know that pre-competitive consortia work when partners come together that are equally motivated to make a difference to patients,” said Peter Kotsonis, PhD, executive director of the UCSF Office of Strategic Alliances (Innovation Ventures).
Pharmaceutical companies that join the consortium will enrich the program by funding more studies, which benefits UCSF by streamlining the funding process.
“Our Immunology Team at Lilly is deeply honored to be the foundational partner for the AutoImmunoprofiler initiative. We look forward to collaborating with the world class scientists and clinicians at UCSF to better understand autoimmune disease at the cellular and molecular level,” said Ajay Nirula, MD, PhD, vice president of immunology at Eli Lilly and Company.
This kind of collaboration is also better for patients because the data-sharing model encourages basic researchers to develop practices that facilitate rapid practical application – it speeds the creation of new drugs and identifies old drugs that may be utilized in new ways.
“We’re setting ourselves up at the Parnassus Heights Campus to be the clinical–translational pipeline to basic research,” said Roose. “We’re allowing industry and academia to work together and come up with solutions faster.”