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One of JDRF's therapeutic goals is to restore beta cell function in type 1 diabetes (T1D) by replacement/transplantation of beta cells/islets. Pancreatic islet transplantation has been efficacious in selected patients in improving metabolic control and quality of life, and in preventing severe hypoglycemia in patients with medically unstable T1D. Despite improvements in cadaveric pancreas procurement, islet isolation, and islet purification, major scientific and technical challenges remain that must be addressed before beta cell replacement could be widely incorporated into the clinical management of established T1D; examples include serious side effects from chronic immunosuppression and the insufficient human islet supply from cadaveric pancreata. JDRF's role is to enable the scientific community to address these challenges with the ultimate goal of developing safe and effective beta cell replacement approaches available to large numbers of individuals with T1D.

One of JDRF's therapeutic goals is to restore beta cell function in type 1 diabetes (T1D) by replacement/transplantation of beta cells/islets. Pancreatic islet transplantation has been efficacious in selected patients in improving metabolic control and quality of life, and in preventing severe hypoglycemia in patients with medically unstable T1D. Despite improvements in cadaveric pancreas procurement, islet isolation, and islet purification, major scientific and technical challenges remain that must be addressed before beta cell replacement could be widely incorporated into the clinical management of established T1D; examples include serious side effects from chronic immunosuppression and the insufficient human islet supply from cadaveric pancreata. JDRF's role is to enable the scientific community to address these challenges with the ultimate goal of developing safe and effective beta cell replacement approaches available to large numbers of individuals with T1D.

This FOA invites new applications to participate in the Human Islet Research Network-Consortium on Human Islet Biomimetics (HIRN-CHIB). NIDDK will support the development of a microphysiological system (MPS) that allows the study of interactions between primary human islets or assembled islet spheroids (organoids made up of human beta/alpha/delta/other cells) and immune cells within a 3D microenvironment to mimic aspects of the autoimmune process and its regulation. The ultimate goal will be to create an in vitro human disease model(s) that could recapitulate some aspects of the complex pathophysiology of Type 1 diabetes (T1D), by using T1D patient-derived islets (created using induced pluripotent stem cells (iPSCs) combined with autologous immune components. CHIB is already part of HIRN, whose overall mission is to support innovative and collaborative translational research to understand how human beta cells are lost in T1D, and to find innovative strategies to protect and replace functional beta cell mass in humans.

This Funding Opportunity Announcement (FOA) invites cooperative agreement applications that will contribute to a higher resolution understanding of the physical and functional organization of the human islet tissue environment by describing the composition (cellular and molecular) and function of important components of the pancreatic islet and peri-islet tissue architecture, the cell-cell relationships and means of communications used by cell types and cell subtypes within the pancreatic tissue ecosystem, and/or the contribution of adjacent (including acinar, ductal, lymphatic) and neighboring (intestinal, mesenteric and adipose) tissues to islet cell function and dysfunction. Successful projects will integrate the Human Pancreas Analysis Consortium (HPAC), that will consist of the research teams funded in response to this FOA with the Human Pancreas Analysis Program (HPAP), a resource-generation program that was funded in 2016 in response to RFA-DK-15-027. HPAC will become the fifth consortium of the Human Islet Research Network (HIRN, https://hirnetwork.org/ ). HIRN's overall mission is to support innovative and collaborative translational research to understand how human beta cells are lost in T1D, and to find innovative strategies to protect and replace functional beta cell mass in humans. This FOA will only support studies with a primary focus on increasing our understanding of human tissue structure and function, and human disease biology (as opposed to rodent or other animal models). This FOA is not intended to support the conduct of a clinical trial.

This Funding Opportunity Announcement (FOA) invites cooperative agreement applications that will contribute to a higher resolution understanding of the physical and functional organization of the human islet tissue environment by describing the composition (cellular and molecular) and function of important components of the pancreatic islet and peri-islet tissue architecture, the cell-cell relationships and means of communications used by cell types and cell subtypes within the pancreatic tissue ecosystem, and/or the contribution of adjacent (including acinar, ductal, lymphatic) and neighboring (intestinal, mesenteric and adipose) tissues to islet cell function and dysfunction. Successful projects will integrate the Human Pancreas Analysis Consortium (HPAC), that will consist of the research teams funded in response to this FOA with the Human Pancreas Analysis Program (HPAP), a resource-generation program that was funded in 2016 in response to RFA-DK-15-027. HPAC will become the fifth consortium of the Human Islet Research Network (HIRN, https://hirnetwork.org/ ). HIRN's overall mission is to support innovative and collaborative translational research to understand how human beta cells are lost in T1D, and to find innovative strategies to protect and replace functional beta cell mass in humans. This FOA will only support studies with a primary focus on increasing our understanding of human tissue structure and function, and human disease biology (as opposed to rodent or other animal models). This FOA will not accept applications proposing a clinical trial.

This Funding Opportunity Announcement (FOA) solicits applications for the Consortium on Targeting and Regeneration (CTAR) that supports the development of innovative strategies to increase or protect functional human beta cell mass in patients with Type-1 Diabetes (T1D) through the controlled manipulation of beta cell replication, islet cell plasticity, and the reprogramming of pancreatic non-beta cells into beta-like cells, or through shielding the residual beta cell mass from the autoimmune environment. CTAR is part of the Human Islet Research Network (HIRN).

This Funding Opportunity Announcement (FOA) solicits applications for the Consortium on Targeting and Regeneration (CTAR) that supports the development of innovative strategies to increase or protect functional human beta cell mass in patients with Type-1 Diabetes (T1D) through the controlled manipulation of beta cell replication, islet cell plasticity, and the reprogramming of pancreatic non-beta cells into beta-like cells, or through shielding the residual beta cell mass from the autoimmune environment. CTAR is part of the Human Islet Research Network (HIRN).

This Funding Opportunity Announcement (FOA) invites new and renewal applications to participate in the Consortium on Modeling Autoimmune Interactions (CMAI). CMAI is a component of the Human Islet Research Network (HIRN) that is focused on developing robust systems to measure and model the biology of human type 1 diabetes. Projects will explore and validate research models designed to advance pre-clinical scientific discovery, mechanistic dissection of disease processes, and testing of potential interventions for T1D.

This Funding Opportunity Announcement (FOA) invites new and renewal applications to participate in the Consortium on Modeling Autoimmune Interactions (CMAI). CMAI is a component of the Human Islet Research Network (HIRN) that is focused on developing robust systems to measure and model the biology of human type 1 diabetes. Projects will explore and validate research models designed to advance pre-clinical scientific discovery, mechanistic dissection of disease processes, and testing of potential interventions for T1D. 

The National Institute of Allergy and Infectious Diseases (NIAID) solicits applications from single institutions and consortia of institutions to participate in the Nonhuman Primate Transplantation Tolerance Cooperative Study Group (NHPCSG) program. The NHPCSG is a multi-center, cooperative program for research on nonhuman primate (NHP) models of kidney, pancreatic islet, heart, and lung transplantation. The goals of the NHPCSG are to evaluate the preclinical safety and efficacy of existing and newly developed immune tolerance induction regimens and to elucidate the underlying mechanisms of the induction, maintenance, and/or loss of tolerance in these models. The long-range goal of this program is to develop and evaluate immune tolerance induction regimens that will result in enhanced long-term graft survival in clinical transplantation.

Validated biomarkers that detect risk, stage the disease, and predict its rate of progression in the at-risk setting for T1D are required to conduct more efficient clinical trials. These biomarkers may include markers of beta cell stress, dysfunction, and damage, functional beta cell mass,  autoimmune/inflammatory biomarkers, and/or biomarkers of impaired glucose and metabolic control. While progress has been made in identifying predictive markers for risk of T1D, there may be alternative molecular biomarkers (metabolites, proteomics, gene expression patterns, additional autoantibodies, etc.) that may prove to be expressed earlier, be more highly predictive, and/or more cost effective for detecting risk. Biomarkers that detect activation of innate immunity  or of T cells specific for beta cells, islet inflammation or beta cell stress, dysfunction or damage may be demonstrated to serve this role.

This Funding Opportunity Announcement (FOA) requests applications for the development of medium- to high-throughput "omics" technologies that can be used to explore human pancreatic tissues with single cell- or near single cell- resolution. Successful applicants will join the Consortium on Beta cell Death and Survival (CBDS), whose mission is to identify the mechanisms of beta cell stress and destruction central to the development of Type 1 Diabetes (T1D) in humans, with the long-term goal of protecting the residual beta cell mass in T1D patients as early as possible in the disease process, and preventing the progression towards autoimmunity. CBDS is part of the Human Islet Research Network (HIRN).

This Funding Opportunity Announcement (FOA) requests applications to explore human pancreatic tissues for the discovery of early biomarkers of T1D pathogenesis, the description of specific signaling or processing pathways that may contribute to the asymptomatic phase of T1D, the development of clinical diagnostic tools for the detection and staging of early T1D in at-risk or recently-diagnosed individuals, and/or the identification of therapeutic targets for the development of preventative or early treatment strategies. Successful applicants will join the Consortium on Beta Cell Death and Survival (CBDS), whose mission is to better define and detect the mechanisms of beta cell stress and destruction central to the development of T1D in humans, with the long-term goal of detecting beta cell destruction and protecting the residual beta cell mass in T1D patients as early as possible in the disease process, and of preventing the progression to autoimmunity. The CBDS is part of a collaborative research framework, the Human Islet Research Network (HIRN, https://hirnetwork.org), whose overall mission is to support innovative and collaborative translational research to understand how human beta cells are lost in T1D, and to find innovative strategies to protect and replace functional beta cell mass in humans. This FOA will only support studies with a primary focus on increasing our understanding of human disease biology (as opposed to rodent or other animal models).

This Funding Opportunity Announcement (FOA) requests applications to explore human pancreatic tissues for the discovery of early biomarkers of T1D pathogenesis, the description of specific signaling or processing pathways that may contribute to the asymptomatic phase of T1D, the development of clinical diagnostic tools for the detection and staging of early T1D in at-risk or recently-diagnosed individuals, and/or the identification of therapeutic targets for the development of preventative or early treatment strategies. Successful applicants will join the Consortium on Beta Cell Death and Survival (CBDS), whose mission is to better define and detect the mechanisms of beta cell stress and destruction central to the development of T1D in humans, with the long-term goal of detecting beta cell destruction and protecting the residual beta cell mass in T1D patients as early as possible in the disease process, and of preventing the progression to autoimmunity. The CBDS is part of a collaborative research framework, the Human Islet Research Network (HIRN, https://hirnetwork.org), whose overall mission is to support innovative and collaborative translational research to understand how human beta cells are lost in T1D, and to find innovative strategies to protect and replace functional beta cell mass in humans. This FOA will only support studies with a primary focus on increasing our understanding of human disease biology (as opposed to rodent or other animal models). This FOA will not accept applications proposing a clinical trial.

This Funding Opportunity Announcement (FOA) invites applications from institutions to participate in the Immunobiology of Xenotransplantation Cooperative Research Program (IXCRP), for the development of preclinical porcine-to-nonhuman primate (NHP) models of pancreatic islet, kidney, heart, lung, or liver xenotransplantation. The goals of this program are to: (1) delineate the cellular and molecular mechanisms of xenograft rejection and/or the induction of immune tolerance; (2) develop effective strategies to improve xenograft survival; and (3) characterize and address the physiological compatibility/limitations of xenografts. The long-term goal of this program is to develop strategies for application of xenotransplantation in the clinic.

This Funding Opportunity Announcement (FOA) invites applications from institutions to participate in the Immunobiology of Xenotransplantation Cooperative Research Program (IXCRP), for the development of preclinical porcine-to-nonhuman primate (NHP) models of pancreatic islet, kidney, heart, lung, or liver xenotransplantation. The goals of this program are to: (1) delineate the cellular and molecular mechanisms of xenograft rejection and/or the induction of immune tolerance; (2) develop effective strategies to improve xenograft survival; and (3) characterize and address the physiological compatibility/limitations of xenografts. The long-term goal of this program is to develop strategies for application of xenotransplantation in the clinic.

NIDDK requests applications to join a new research consortium "Microphysiological Systems (MPS) for Modeling Diabetes (MPS-MOD)". NIDDK will support the development and validation of human tissue chips that closely mimic the normal physiology of key metabolic tissues, including the pancreatic islet, liver, skeletal muscle, and white adipose tissue (WAT). Experimental designs for the MPS-MOD platforms should incorporate strategies to measure pathophysiological changes associated with metabolic disease, including the impact of immune cells on metabolic dysfunction. Once developed, these multi-dimensional MPS-MOD platforms will serve as the foundation for NIDDK's advanced strategy to identify new and novel therapeutics for diabetes. The utility and validity of model systems developed under this initiative will be measured, in part, through the ability of known diabetes therapeutic agents and biomarkers to influence biology of the system, using best practices and rigorous study design. The need for high-quality, well-characterized isogenic/patient derived iPSC (induced pluripotent stem cell) lines and standardized differentiation procedures is a critical step in turning disease-specific lines into tools for discovery. In the future, iPSC-based human tissue chips could play a central role in drug development, testing, screening, drug repurposing and toxicity testing.