The Mechanism of Hematological Abnormalities in Systemic Autoimmunity
NIAMS - National Institute of Arthritis and Musculoskeletal and Skin Diseases
About This Grant
ABSTRACT Systemic autoimmune diseases such as systemic lupus erythematosus (SLE) are mediated by autoantibodies against key tissue constituents, accompanied by the activation of innate immune system. In addition, systemic autoimmunity is frequently associated with hematological complications such as lymphopenia, anemia and/or thrombocytopenia, which can be debilitating and even life-threatening. These abnormalities are typically considered as isolated symptoms caused by autoantibodies against the respective blood cell types, and are treated by immunosuppressive therapies. On the other hand, it is possible that frequent hematopoietic abnormalities in SLE may reflect a defect in the source of hematopoiesis, i.e. hematopoietic stem cells (HSC) and/or progenitors. This model has important implications for the pathogenesis and treatment of SLE; however, it remains to be supported by genetic and mechanistic evidence. Our preliminary studies suggest that the bone marrow from mice with SLE-like disease showed impaired ability to reconstitute irradiated recipients. Moreover, HSCs in moribund mice showed increased proliferation and upregulation of transcripts associated with stem cell exhaustion. We therefore hypothesize that clinical SLE-like disease impairs the activity of HSC, which may further exacerbate hematological abnormalities and inflammation. This hypothesis will be tested using two Specific Aims. In Aim 1, we will characterize HSC impairment in a mouse model of SLE-like disease, including its cell-extrinsic nature and relevance to endogenous hematopoiesis. In Aim 2, we will characterize the epigenome of disease-affected HSC, as well as molecular pathways that cause HSC impairment in this model. Collectively, these studies may support the paradigm of impaired HSC activity as a source of hematopoietic abnormalities and "trained autoimmunity" in SLE. As such, they may pave the way for future studies of stem/progenitor function in human SLE and of its potential therapeutic modulation.
Grant Summary
The Mechanism of Hematological Abnormalities in Systemic Autoimmunity is a NIAMS - National Institute of Arthritis and Musculoskeletal and Skin Diseases grant providing up to $166K for university, nonprofit, healthcare org. Applications are due 2027-01-31 (open). Check eligibility and apply with FindGrants.
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How to Apply
Up to $166K
2027-01-31
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- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
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The Mechanism of Hematological Abnormalities in Systemic Autoimmunity: Frequently Asked Questions
Who is eligible for the The Mechanism of Hematological Abnormalities in Systemic Autoimmunity?
The Mechanism of Hematological Abnormalities in Systemic Autoimmunity is offered by NIAMS - National Institute of Arthritis and Musculoskeletal and Skin Diseases and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the The Mechanism of Hematological Abnormalities in Systemic Autoimmunity provide?
The Mechanism of Hematological Abnormalities in Systemic Autoimmunity provides up to $166K per award from NIAMS - National Institute of Arthritis and Musculoskeletal and Skin Diseases. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the The Mechanism of Hematological Abnormalities in Systemic Autoimmunity deadline?
Applications for The Mechanism of Hematological Abnormalities in Systemic Autoimmunity are due 2027-01-31 (open). Because deadlines can change, verify the date with the funder, NIAMS - National Institute of Arthritis and Musculoskeletal and Skin Diseases, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the The Mechanism of Hematological Abnormalities in Systemic Autoimmunity?
To apply for The Mechanism of Hematological Abnormalities in Systemic Autoimmunity, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIAMS - National Institute of Arthritis and Musculoskeletal and Skin Diseases.