Researchers receive seven awards totaling more than $5 million in Q1 and Q2 2023
Today, the Benaroya Research Institute (BRI) announced new research grants awarded in Q1 and Q2 of 2023, including a $3.1 million grant to study inflammatory memory and how to break the cycle of inflammation in patients with skin diseases like psoriasis and atopic dermatitis, funded by the National Institutes of Health (NIH). All grants awarded to BRI in Q1 and Q2 totaled more than $5 million.
The $3.1 million NIH grant (R01AI169893) is led by BRI scientists Daniel Campbell, PhD, and Hannah DeBerg, PhD in collaboration with Dr. Iris Gratz, PhD, from the University of Salzburg in Austria, and aims to address gaps in our knowledge of the body’s inflammatory responses by evaluating how T cells and other structural cells communicate with each other. By studying samples from patients with common skin conditions like psoriasis and atopic dermatitis, the research team will assess hallmarks of the body’s “inflammatory memory”, the process by which inflammation leaves a lasting mark on a tissue that can modify subsequent inflammatory and tissue-repair responses. Ultimately, this work will help develop a better understanding of how inflammatory memory works in tissues like the skin in hopes of one day breaking the inflammatory cycle for patients with these skin conditions.
“We are diving deep into the body's inflammatory language,” said Campbell. “This research will help us understand how inflammation changes over time in conditions like psoriasis and atopic dermatitis. Ultimately, this knowledge could equip us with the ability to disrupt this destructive cycle of inflammation, providing hope for those grappling with such skin conditions.”
In addition to these awards, BRI team members received six other grants supporting research examining colorectal cancer, Type 1 diabetes, multiple sclerosis and more.
“Understanding the complex human immune system means studying it from multiple angles, perspectives and disease areas,” said Jane Buckner, MD, president of BRI. “Collectively, these efforts demonstrate BRI’s capacity to predict, prevent, reverse and cure diseases of the immune system.”
Details of the six additional grants awarded to BRI in Q1 and Q2 2023 include:
Role of B cells in modulating metabolic pathways of pathogenic CD4 T cells in murine model of multiple sclerosis
Yevgeniy Yuzefpolskiy, PhD (Mentor: Estelle Bettelli, PhD)
$212,153
Dr. Yuzefpolskiy’s work aims to uncover a potentially significant building block for the next generation of multiple sclerosis (MS) therapies. His project seeks to understand specific metabolic requirements for T and B cells — believed to be a primary driver of nervous system destruction in MS — and whether disrupting those metabolic requirements may suppress the cells’ pathogenic function.
Sponsor: National Multiple Sclerosis Society
Defining and applying neo-epitope specific TCRs for engineered cell therapy
Aisha Callebaut, PhD (Mentor: Eddie James, PhD)
$188,886
The development of Type 1 diabetes is caused by T cell-mediated destruction of insulin-producing beta cells. This collaborative project seeks to identify specific T cell receptor sequences that preferentially recognize these stress-modified beta cell proteins and to leverage these to develop an engineered cell therapy capable of halting the progression of Type 1 diabetes. Cells will then be handed off for in vivo studies to evaluate their ability to home to the pancreas and oppose the destruction of beta cells in pancreatic islets. Based on those findings, the team will identify lead candidates to advance toward the development of a cell-based clinical therapeutic.
Sponsor: JDRF
Regulation of TLR signaling in anti-commensal B cell responses and mucosal inflammation
Adam Lacy-Hulbert, PhD, Oliver Harrison, DPhil
$474,375
Mucous membranes, which line parts of the body such as the mouth, nose, and eyelids, are home to a variety of bacteria, viruses and other microorganisms which rely on interactions with the body’s immune system. There is a pressing need to better understand the details of these interactions, as well as investigate if and how these interactions may be involved in inflammation and immune pathology. This project will build on prior findings that demonstrated the involvement of toll-like receptor signaling (TLR), mediated by surface receptor integrin αvβ3, in this antibody generation process. Researchers will test the hypothesis that αvβ3 regulates B cell responses to bacteria to maintain a defense against infection while preventing overactive inflammatory responses.
Sponsor: National Institutes of Health (R21AI171921)
Cutaneous T cell dependent regulation of scleroderma-associated fibroblasts
Peter Morawski, PhD
$200,000
This project aims to identify the individual components of the immune system that drive different aspects of scleroderma, a systemic inflammatory disease. Specifically, researchers will assess how T cells can promote distinct gene expression profiles in the skin. By identifying the individual components of the immune system that may drive different aspects of scleroderma, the team hopes to predict how the disease will progress in different people.
Sponsor: National Scleroderma Foundation
Identification of novel targets in a unique subset of Tregs for therapies for colorectal cancer
Kazushige Ninomiya, PhD
$299,850
Prior research from the Ziegler lab revealed a potential therapeutic target in a unique subset of regulatory T cells (Tregs) for colorectal cancer in humans and mice. This grant will allow researchers to expand that work to further characterize these Tregs (in models) and screen human patients with colorectal cancer across disease stages. Ideally, this research will lay the foundation for new therapies and diagnostic approaches for patients with colorectal cancer.
Sponsor: Andy Hill CARE Fund
Foxp3 isoforms and UVB-induced skin inflammation expression
Steve Ziegler, PhD
$476,575
Ultraviolet B light is a common environmental trigger that can induce skin inflammation and flares in several autoimmune diseases. This work will provide insights into the role of Foxp3∆E2 Treg function and the development and progression of inflammatory skin disease.
Sponsor: National Institutes of Health (R21AI178426)
For more information on BRI and its research efforts, visit www.benaroyaresearch.org.
