Colton Center for Autoimmunity awards grants to six Yale projects

The Colton Center for Autoimmunity at Yale has awarded grant funding to six innovative research projects that exhibit the potential to develop new diagnostics and therapeutics and to provide new insights into the mechanistic underpinnings of autoimmune diseases.

Established in 2019 with a generous gift from Judith and Stewart Colton, the center is dedicated to the advancement of translational Yale research in autoimmune diseases with the goal to develop therapeutics, diagnostics, and prophylactics. It provides strategic support of early-stage, innovative research that has potential for commercialization, but which otherwise might fail to develop due to lack of funding.

This year’s funded projects and the lead researchers include:

• Targeting HIF1 to treat discoid lupus erythematosus: Dr. Alicia Little, assistant professor of dermatology, will explore the role and therapeutic targeting of the transcription factor HIF1 in T cell-driven skin damage in lupus.
• Unbiased characterization of the antigenic targets driving autoimmunity: Dr. David Hafler, the William S. and Lois Stiles Edgerly Professor of Neurology and professor of immunobiology, will sequence T cell receptors (TCR) from migrating T cells and conduct personalized screens of self-antigens to deorphan TCRs from multiple sclerosis patients to identify antigens for immunotherapy.
• Defining roles of a targetable kinase in autoantibody production: Carrie Lucas, associate professor of immunobiology, will investigate how human kinase deficiency illuminates B cell biology with the goal to identify a therapeutic target for manipulation of the pathogenic autoantibody response in lupus.
• Pathogenic antibodies in rapid-onset neuroinflammatory pediatric obsessive-compulsive disorder: Towards clarification of nosology and development of novel diagnostic tests: Dr. Christopher Pittenger, the Elizabeth Mears and House Jameson Professor of Psychiatry, will use innovative methodologies to identify autoantibodies that may contribute to rapid-onset pediatric obsessive-compulsive disorder, with the goal of moving towards precision diagnostics and personalized treatments.
• Molecular imaging in autoimmunity: Dr. Mehran Sadeghi, professor of medicine (cardiovascular medicine), will develop a novel, non-invasive molecular imaging approach in autoimmunity.
• Novel SPECT/CT imaging to evaluate a PPARγ agonist for reversal of pulmonary hypertension in a systemic sclerosis murine model: Stephanie Thorn, a research scientist in medicine (cardiovascular medicine), will evaluate novel SPECT non-invasive imaging techniques for fibrosis and angiogenesis to assess disease progression and potential therapy in systemic sclerosis.

More than 23 million individuals in the United States have autoimmune diseases, and the numbers continue to rise annually. A lack of clear understanding of their causes limits the development of safe and effective therapies and diagnostic tools. Investigators supported by the Colton Center will address this knowledge gap.

Yale researchers say the support from the new center has afforded them the opportunity to conduct high-risk translational, potentially transformative, research that is too early for consideration by extramural funding agencies or industry partnering. Since its inception in 2019 and initiation of investigator funding in 2020, the center has supported 15 projects, including ones that have led to intellectual property development.

“The Colton Center has had a positive impact on our research program that goes beyond funding. It has directly influenced our scientific direction by encouraging us to examine molecular processes underlying autoimmunity,” said Anna Marie Pyle, Sterling Professor of Molecular, Cellular, and Developmental Biology and professor of chemistry at Yale. “Until recently, the work in my lab focused exclusively on the opposite problem: How the innate immune system is activated in response to viral infection. But now we are asking what happens when these same antiviral pathways become dysregulated, leading to autoimmune disorders.

“By learning how to fully tune the innate immune system (developing tools to turn it off and to turn it on) one can develop robust pharmacological approaches to autoimmunity, antitumor responses, and pan-viral therapeutics.”

The center also encourages cross-disciplinary research that actively bridges the gaps between research and application, said Dr. Joseph Craft, the Paul B. Beeson Professor of Medicine at Yale, professor of immunobiology, and the center’s director.

“In conjunction with a diverse advisory committee of experts from academia, venture firms, the pharmaceutical industry, and technology transfer at Yale Ventures, we evaluated many proposals from diverse academic disciplines at Yale that address unanswered questions in the autoimmune field,” said Craft, who also runs an independent research laboratory dedicated to fundamental immunology and the study of systemic lupus erythematosus. “I am delighted with the array of autoimmunity-focused research The Colton Center at Yale was able to award this year, and we look forward to tracking their progress.”

Funded projects are monitored for translational potential, development of intellectual property, and partnering opportunities for startups, biotechnology firms, and pharmaceutical companies.

“We are so appreciative of support from the Colton family and the Colton Center for Autoimmunity at Yale,” said Dr. Mary Tomayko, associate professor of dermatology and of pathology at Yale and director of the Yale Immunobullous Clinic. “Our goal is to identify novel therapeutic approaches for the treatment of cancer treatment-related autoimmunity of the skin. Colton pilot funding and the astute intellectual critiques of its advisory committee have been critical during the early, precarious stages of this work. Because of Colton support, we are making observations that are already beginning to improve the quality of life of individuals with autoimmunity.”

Dr. Ian Odell, an assistant professor of dermatology, is a grantee with a joint project with Richard Flavell, Sterling Professor of Immunobiology and investigator for the Howard Hughes Medical Institute. “Funding from the Colton Center was instrumental for us to translate our basic science discoveries to development of a novel fibrosis therapeutic,” Odell said. “We highly appreciate the opportunity to move towards making a difference for our patients that the generous funding has allowed.”

The Colton Center works closely with Yale Ventures toward the identification, protection, and licensing of intellectual property resulting from the funded projects. “Yale Ventures is dedicated to supporting translational research that addresses widespread health challenges like autoimmune diseases, so we are grateful for the work Dr. Craft is doing to make strides in this space,” said Josh Geballe, managing director of Yale Ventures. “Congratulations to each of the 2022 grantees. We are looking forward to watching you advance your projects for optimal impact on patient outcomes.”

View more information about the 2022 grantees and their research, previous grantees, and the Colton Center for Autoimmunity at Yale.

A new round of funding will be offered in 2023, with request for proposals to be posted fall 2022.