Deadline: LOI due 12:00pm PST on April 30, 2025
Background
The Leona M. and Harry B. Helmsley Charitable Trust’s (Helmsley) Type 1 Diabetes (T1D) Program aims to support the discovery and development of new therapies to prevent or delay T1D and the identification and validation of biomarkers to predict disease initiation and progression.
T1D is a complex autoimmune disease where insulin-producing beta cells in the pancreas are targeted by immune cells. The predisposing factors, triggers, and other elements that affect disease pathogenesis in humans are not yet fully identified. Understanding these drivers of disease could lead to discoveries of new drug targets, guide intervention strategies to halt the disease, or improve prediction of disease development.
To date most T1D preclinical and clinical research has focused on the role T cells play in disease pathogenesis. However, innate immune cells are the first and most abundant type of immune cells in the pancreas, especially in individuals with T1D. Moreover, data, mostly generated from animal experiments, suggests that these cells might play different roles in T1D: from activating T cells and/or recruiting them to the pancreatic islets, to promoting inflammation or inducing immune tolerance. However, what leads to an increase in innate immune cells in the pancreas during T1D, its significance, and what role these cells play in disease in humans is not yet fully understood.
Request for Proposals
To address this gap, the Helmsley T1D Program seeks to support studies that aim to evaluate or modulate the function of innate immune cells and pathways in T1D, with an emphasis on human disease during relatively early stages of disease (i.e., autoantibody positivity through early onset of clinical disease).
Of specific interest are research plans that include:
- Analyzing the type and function of innate cells (e.g. macrophages, dendritic cells, natural killer cells) present in the pancreas and their interactions with other cells, tissue-resident or otherwise;
- Investigating mechanisms of T1D pathogenesis that involves innate immunity;
- Identifying or validating biomarkers of disease progression or response to treatment based on innate immune cells;
- Identifying or validating therapeutic innate immune cell targets; and
- Developing or validating preclinical or clinical therapies to prevent or delay T1D that target or use innate immune cell pathways.
Proposed activities can include, but are not limited to:
- Generation or testing of hypotheses using human samples;
- Profiling or functional analysis of innate immune cells in pancreas samples and pancreas slices;
- Analysis of preexisting relevant data sets, either publicly available or generated by the applicant; and
- Preclinical or clinical activities that advance or build evidence for a specific therapeutic concept based on existing knowledge of the role of innate immunity in T1D.
Like other fields, scientific research in T1D has been challenged by limited access to human samples. To facilitate potentially impactful studies, Helmsley has partnered with two leading T1D networks, the Network for Pancreatic Organ donors with Diabetes (nPOD and INNODIA, to enable access to disease relevant samples and connected clinical and biological data in relation to this RFP. Applicants who proceed to the full proposal stage with a project that includes access to nPOD or INNODIA samples will work with the relevant network team to hone final research plans and access to samples.
For more information, please see the foundation webpage.