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View full policyDetermining the role of ABHD17 in Pemphigus Vulgaris
About This Grant
Abstract Pemphigus is a family of rare, potentially life-threatening epidermal blistering diseases. Pemphigus vulgaris (PV) is an autoimmune disease characterized by painful blisters and erosions of the skin and mucus membranes including the oral cavity. Affected individuals produce autoantibodies targeting the adhesive domain of the desmoglein 3 (Dsg3) adhesion molecule in the desmosomal adhesion complex. PV autoantibodies primarily bind Dsg3 and disrupt cell to cell adhesive contacts between the basal and suprabasal keratinocytes in the epidermis leading to acantholysis and blister formation. Mechanisms regulating desmosome assembly, disassembly and stability are poorly understood. We recently discovered that palmitoylation of several desmosomal proteins, including Dsg3, plays an important role in desmosome assembly and stability. Palmitoylation is a reversible post-translational modification whereby the addition of a 16-carbon moiety (palmitate) is enzymatically added to cysteine residues of substrate proteins in the cytoplasm and can affect protein association with cellular membranes, subcellular localization and/or protein activity. Conversely removal of palmitate by enzymatic depalmitoylation can also influence membrane association, localization and activity. We have identified ABHD17b as a depalmitoylase acting on a desmosomal proteins to disrupt desmosomal adhesion. Our central hypothesis for this project is that inhibition of depalmitoylase enzymes acting upon desmosomal proteins will stabilize the desmosome and protect keratinocytes from disruption by PV autoantibodies. To gain insight into the role of ABHD17 proteins in this process, we propose the following aims. 1) Generate expression systems to alter the expression and activity of ABHD17 proteins in cultured cells and generate a panel of murine monoclonal antibodies specific for ABHD17 proteins. 2) Determine the role of ABHD17b in protecting keratinocytes from PV induced cell fragmentation. 3) Determine the substrate landscape for ABHD17 family depalmitoylases in keratinocytes utilizing a tandem mass tag mass spectroscopy approach. These aims build on our preliminary findings that ABHD17b acts to depalmitoylate desmosomal components and take advantage of our strengths in generating expression systems as well as producing and characterizing highly specific monoclonal antibodies specific for ABHD17 family members. Additionally, we will begin to identify the landscape of ABHD17 depalmitoylase substrates in keratinocytes and identify additional substrates that are potentially co-regulated with the desmosomal components. The depalmitoylases are attractive druggable targets that have the potential to be novel therapeutic targets in the treatment of pemphigus.
Grant Summary
Determining the role of ABHD17 in Pemphigus Vulgaris is a OD - NIH Office of the Director grant providing up to $158K for university, nonprofit, healthcare org. Applications are due 2027-06-30 (open). Check eligibility and apply with FindGrants.
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How to Apply
Up to $158K
2027-06-30
- 1Confirm your organization is eligible for Determining the role of ABHD17 in Pemphigus Vulgaris from OD - NIH Office of the Director, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 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.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to OD - NIH Office of the Director before the deadline.
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Determining the role of ABHD17 in Pemphigus Vulgaris: Frequently Asked Questions
Who is eligible for the Determining the role of ABHD17 in Pemphigus Vulgaris?
Determining the role of ABHD17 in Pemphigus Vulgaris is offered by OD - NIH Office of the Director 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 Determining the role of ABHD17 in Pemphigus Vulgaris provide?
Determining the role of ABHD17 in Pemphigus Vulgaris provides up to $158K per award from OD - NIH Office of the Director. 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 Determining the role of ABHD17 in Pemphigus Vulgaris deadline?
Applications for Determining the role of ABHD17 in Pemphigus Vulgaris are due 2027-06-30 (open). Because deadlines can change, verify the date with the funder, OD - NIH Office of the Director, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Determining the role of ABHD17 in Pemphigus Vulgaris?
To apply for Determining the role of ABHD17 in Pemphigus Vulgaris, 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 OD - NIH Office of the Director.