Cellular and Molecular Mechanisms of Early onset colorectal cancer
About This Grant
Project Summary Since 1990, the overall incidence of late onset colorectal cancer (LOCRC ≥50 yrs. old) has decreased. However, these rates have steadily increased in younger individuals (<50 yrs. old). The cellular and molecular mechanisms underlying early onset CRC (EOCRC), and its poorer survival outcomes in men are unclear. Approximately 80% of EOCRC tumors are sporadic, arising from acquired genetic mutations. Epidemiological studies have noted a higher incidence and advanced-stage cancers in males with EOCRC compared to females, with males exhibiting a larger Wnt/β-catenin signaling component, a major driver of cancer stem cell (CSC) population expansion. The enzyme asparagine synthetase (ASNS) links CSC function and sex differences to EOCRC development. Targeting ASNS-expressing ISCs could offer therapeutic potential as high tumoral asparagine (Asn) levels correlate with cancer aggressiveness in male EOCRC alone. The objective of this proposal is to investigate sex- dependent mechanisms in EOCRC progression. My central hypothesis is that ASNS drives CSC expansion and tumorigenesis in EOCRC, which is enhanced in males. I will test my hypothesis through the following Specific Aims. Aim 1 (K99 phase): Analyze untargeted metabolomics data of 372 paired CRC and normal mucosa tissues from EOCRC and LOCRC. I will perform whole exome sequencing and use machine learning to identify unique mutational signatures and metabolites associated with EOCRC. Aim 2 (K99 phase): Develop patient- derived organoids (PDOs) from EOCRC/LOCRC samples, supplement them with Asn at varying concentrations, and examine organoid number, growth, size, and crypt budding. I will assess CSC dynamics in PDOs using time- of-flight mass cytometry (CyTOF). I will delete ASNS in PDOs using CRISPR-Cas9 and test the sex-specific effects of ASNS loss on PDO growth and crypt budding. Aim 3 (R00 phase): Evaluate the effects of ASNS deletion on tumor growth and survival using a patient-derived xenograft model. Investigate tumor heterogeneity using single cell/nuclei RNA-Sequencing and spatial transcriptomics. This research will provide novel insights into the sex-dependent roles of ASNS and Asn in ISC niche expansion during EOCRC progression, improving our understanding of EOCRC development. The training will equip me with skills in machine learning, stem cell biology, and tumor heterogeneity, which will be foundational for developing pre-clinical models of EOCRC in my future independent laboratory.
Grant Summary
Cellular and Molecular Mechanisms of Early onset colorectal cancer is a NCI - National Cancer Institute grant providing up to $130K for university, nonprofit, healthcare org. Applications are due 2028-05-31 (open). Check eligibility and apply with FindGrants.
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How to Apply
Up to $130K
2028-05-31
- 1Confirm your organization is eligible for Cellular and Molecular Mechanisms of Early onset colorectal cancer from NCI - National Cancer Institute, 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 NCI - National Cancer Institute before the deadline.
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Cellular and Molecular Mechanisms of Early onset colorectal cancer: Frequently Asked Questions
Who is eligible for the Cellular and Molecular Mechanisms of Early onset colorectal cancer?
Cellular and Molecular Mechanisms of Early onset colorectal cancer is offered by NCI - National Cancer Institute 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 Cellular and Molecular Mechanisms of Early onset colorectal cancer provide?
Cellular and Molecular Mechanisms of Early onset colorectal cancer provides up to $130K per award from NCI - National Cancer Institute. 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 Cellular and Molecular Mechanisms of Early onset colorectal cancer deadline?
Applications for Cellular and Molecular Mechanisms of Early onset colorectal cancer are due 2028-05-31 (open). Because deadlines can change, verify the date with the funder, NCI - National Cancer Institute, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Cellular and Molecular Mechanisms of Early onset colorectal cancer?
To apply for Cellular and Molecular Mechanisms of Early onset colorectal cancer, 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 NCI - National Cancer Institute.