Benaroya Research Institute Awarded $11.4 M NIH U19 Grant to Profile Respiratory Viral Infections in Vulnerable Populations and $3.9M NIH R01 Grant to Develop New Treatments for Type 1 Diabetes
BRI researchers receive six awards totaling more than $17.1M in Q1 2022
Today, the Benaroya Research Institute (BRI) announced new research grants, including a $11.4 million-dollar U19 grant to study respiratory viral infections in vulnerable populations and a competitive $3.9M Research Project Grant (R01), both funded by the National Institutes of Health (NIH). All grants awarded to BRI in Q1 2022 totaled more than $17.1 million dollars.
The NIH-funded U19 grant program supports collaborative projects involving multiple institutions. This five-year award, led by Carmen Mikacenic, MD, and Matt Altman, MD, MPhil, will study immune system changes upon infection with acute respiratory viral infections (ARVI) in vulnerable populations like children with allergies, asthma and obesity and adults with rheumatoid arthritis. Given the collaborative nature of the U19 grant, BRI will share its longitudinal findings with the Human Immunology Project Consortium (HIPC), a network of researchers established to create a public resource that characterizes the diverse states of the human immune system.
“We are thrilled to begin this work that will generate an enormous amount of cutting-edge data that furthers our understanding of the human immune system in partnership with the HIPC,” said Mikacenic. “This research will help contribute to a baseline understanding of how the immune system responds to infection in these understudied populations.”
President of BRI Jane Buckner, MD, will lead the $3.9 million-dollar R01 grant in collaboration with Co-Principal Investigator Dr. David Rawlings from Seattle Children’s Research Institute and Dr. Eddie James of BRI. The four-year study aims to use novel gene editing technology to develop engineered regulatory T cells (EngTregs) that will go to the pancreatic islet where the engineered cells will suppress autoimmunity and promote the health of beta cells (β-cells), which are destroyed in someone with type 1 diabetes (T1D). Buckner and her collaborators will create EngTregs that recognize islets that are under stress and upon arrival within the islets deliver a payload that will suppress ongoing inflammation and/or promote β-cell survival and growth.
"BRI has a robust track record studying T1D and this work will build on our understanding of the destruction of β-cells and working with our collaborators at Seattle Children’s Research Institute and their expertise in T cell gene editing, we aim to uncover ways to promote healthy islet function and protection,” said Buckner.
In addition to these awards, BRI team members received four other NIH-funded grants supporting research examining Crohn's disease, lung immune responses, viral infections and more.
“BRI is on the frontlines of human immune system research and innovation and these recent awards reflect our diverse, rich expertise and collaborative approach,” said Buckner.
Details of the four additional grants awarded to BRI in Q1 2022 include:
Development and functions of tissue resident memory T cells during EAE
Estelle Bettelli, PhD
Experimental autoimmune encephalomyelitis (EAE) is a model for studying multiple sclerosis (MS) mechanisms and for testing potential drug therapies. There is little information about the tissue resident memory T cells (TRMs) that are in the central nervous system (CNS) and the cerebrospinal fluid (CSF) of MS patients. Using a newly developed research model in which the investigator can identify, track, characterize and eliminate TRMs during the course of EAE, Dr. Bettelli will determine whether these TRMs express unique markers that distinguish them from other memory T cells, characterize their distribution and kinetics during EAE, and establish whether they recirculate and participate in disease progression and relapses. Gaining a better understanding of how memory T cells promote chronic autoimmunity may lead to the development of new therapies for MS.
Regulation of Tfh function in autoimmunity by TSLP
Steve Ziegler, PhD
The Ziegler lab has shown that the cytokine, thymic stromal lymphopoietin (TSLP), plays a significant role in the development of spontaneous germinal centers (Spt-GCs), which are correlated with autoimmunity and the production of autoantibodies. TSLP is also critical for the differentiation of T follicular helper cells (Tfh). With this grant, the lab will determine the role of TSLP in Tfh development and function, and the role of this cytokine signal in autoimmune-prone mice and their development of Spt-GCs.
Characterization of E. coli-specific T cells in Crohn's disease
James Lord, MD, PhD
Dr. Lord will study antigen-specific T cells that recognize the OmpC peptide from E. coli, fail to make IL-10 in Crohn’s disease and whether the absence of this cytokine is the mechanism by which tolerance to gut flora is lost. This project will provide the foundation for determining how the loss of IL-10 cytokine expression in Crohn’s patients contributes to disease development and progression.
Modulation of Lung Immune Responses to Viral Infection – Supplement
Carmen Mikacenic, MD
Drs. Mikacenic and Ziegler will study the proteomics (the protein profile), autoantibodies, and cellular immune responses in plasma and airway samples from subjects with and without COVID-19. The goal is to identify immune factors that predispose patients to the development of lung fibrosis, an important sequela of COVID-19.
Research reported in this release was supported by the National Institutes of Health under award numbers: U19AI167891 (National Institute of Allergy and Infectious Diseases), R01DK132593 (National Institute Of Diabetes And Digestive And Kidney Diseases), R21NS127190 (National Institute of Neurological Disorders and Stroke), R21AI169418 (National Institute of Allergy and Infectious Diseases), R21AI164332 (National Institute of Allergy and Infectious Diseases), and U19AI142733-03S2 (a National Institute of Allergy and Infectious Diseases -funded subaward from The Jackson Laboratory). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.