The MAST Genes Research Foundation is pleased to announce the 2026 MAST Genes Pilot Grant Program, which will support two investigator-initiated research projects aimed at advancing the biological understanding of the MAST genes and/or accelerating the discovery or development of therapeutic approaches.

This pilot grant is intended to generate high-impact preliminary data, support novel or underexplored approaches, and position investigators for future external funding. 

Background

The MAST family of microtubule-associated serine-threonine kinases performs distinct and overlapping roles in the developing and mature brain. To date, MAST1 and MAST3 have been conclusively linked to neurodevelopmental disorders: MAST1 variants are associated with structural brain malformations, and MAST3 variants cause developmental and epileptic encephalopathy. The phenotypic spectrums associated with MAST2 and MAST4 variants are currently being defined.

While microtubules mediate core cellular processes in the nervous system, including neuronal migration, structural scaffolding, and synapse formation, the precise pathogenic mechanisms by which MAST family mutations drive neuronal dysfunction remain largely uncharacterized. Consequently, no disease-modifying therapies exist, and current clinical management is limited to supportive care.

Important gaps remain across fundamental biology, genotype-phenotype correlations, variant-specific functional consequences, biomarker identification, and targeted therapeutic strategies. Addressing these gaps is critical to advancing translational research and improving patient outcomes.

Research Priorities:

Proposed projects must be directly relevant to the biology and clinical manifestations of MAST1, MAST2, MAST3, and/or MAST4 related neurodevelopmental disorders, and must align with at least one of the priority areas below.

Priority will be given to projects that address:

1. Disease mechanisms and variant-level biology

Studies that advance understanding of how pathogenic or likely pathogenic variants in MAST1-4 alter protein expression, kinase activity, downstream signaling, or neuronal phenotypes. Topics of interest include: 

• Identification of direct substrates, binding partners, and signaling cascades involving MAST kinases.
• Functional characterization of patient-observed variants, especially recurrent mutations.
• Integration of variant functional data with clinical phenotype data to delineate genotype-phenotype correlations within or across the MAST gene family. 
• Development, validation, and utility of patient-derived or engineered cellular and animal models.

2. Therapeutic approaches

Exploratory or proof-of-concept studies aimed at therapeutic discovery and target validation for MAST1 and MAST3 related disorders, including:

• Small-molecule screening, kinase modulatory discovery, or drug repurposing evaluations.
• Development and validation of gene-targeted or RNA-based therapeutic strategies (e.g. ASO, siRNA, gene replacement, or editing approaches).
• Optimization of robust, disease-relevant cell or biochemical assays suitable for high throughput screening (HTS).

3. Multi-Investigator and Interdisciplinary Collaboration

Applications that address Priority 1 or 2 through active collaboration across multiple investigators, laboratories, or institutions, particularly those bridging basic neurobiology with clinical research.

Award Amount and Duration:

• Two awards of $50,000 total costs
• Project duration: up to 12 months
• Indirect costs are not permitted.

Eligibility 

• Investigators holding a faculty-level appointment at an academic institution
• Investigators in a senior position at a nonprofit research organization or foundation
• International applicants are welcome
• Early career investigators and postdoctoral fellows may apply, provided the application includes      documented institutional and mentor support.

Letter of Interest Instructions

All applicants must first submit a Letter of Interest (LOI) to be reviewed for consideration of a full application submission. Please visit our website to submit your LOI, which can also be found here.

Format for the 1‐page LOI:

• Project title
• Principal Investigator and institution
• Overall goal of the project
• Clear statement of relevance to MAST Genes and this RFA
• Brief background
• Specific aims listed succinctly
• High-level project timeline and requested budget

LOI Due Date: LOI document is to be uploaded no later than 8pm (ET) on AUGUST 28 2026, via ONLINE FORM. Applicants will be notified via email with a decision regarding their LOI, which, if successful, will invite the applicant to submit a full application.

Please review RFA here before applying.