Wednesday, December 17, 2025 12/17/2025

Investigating the role of chromatin-associated RNA processing in Early B-cell development

Award Number: F31AI188882
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 12/01/2024
PERIOD OF PERFORMANCE END DATE: 11/30/2027

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Investigating the role of chromatin-associated RNA processing in Early B-cell development - Project Summary B-cells are unique among mammalian cells because of their ability to undergo programmed genomic rearrangements. The first of these rearrangements is called VDJ recombination and is primarily responsible for generating the vast diversity of antibodies seen in nature. This is critical for the development of the adaptive immune system, but generating double-stranded DNA breaks is an enormous risk to the cell, therefore VDJ recombination must be tightly regulated. My lab has previously shown that VDJ recombination depends on the RNA exosome’s 3’ RNA processing activity. After losing the RNA exosome Pro-B-cells accumulate non-coding RNAs throughout the IgH locus. My project seeks to build upon these findings by finding the exact mechanism through which the RNA exosome and RNA helicases act during VDJ recombination. I will use novel mouse models to investigate RNA helicases that have been shown to act on chromatin-associated RNAs that I hypothesize play a role in VDJ recombination. I will confirm these results in a RAG-inducible in-vitro system to confirm that off-target genomic instability is not causing the defect in VDJ recombination and investigate the transcriptional status of RNA processing deficient Pro-B-cells. After these experiments, I will perform experiments to identify the status of the chromatin-associated RNA at the Ig loci and how they affect the frequency and structure of double-strand breaks at recombination signal sequences. Finally, I will attempt to rescue the defect by targeting a dCas9-RNAseH construct to sites with increased chromatin-associated RNAs in helicase or exosome-deficient backgrounds, showing that the helicases and the exosome play an active and direct role in VDJ recombination, independent of their role elsewhere in the genome.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $49,538 )
2026	2026	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Allergy and Infectious Diseases Research	000	2	12/5/2025	NON-COMPETING CONTINUATION	$49,538
														Subtotal = $49,538

Issue Date FY: 2025 ( Subtotal = $49,538 )
2025	2025	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Allergy and Infectious Diseases Research	000	1	11/26/2024	NEW	$48,974
2025	2025	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Allergy and Infectious Diseases Research	001	1	11/26/2024	NEW	$0
2025	2025	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Allergy and Infectious Diseases Research	002	1	7/24/2025	NEW	$564
														Subtotal = $49,538

Grand Total All Awards = $99,076

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Investigating the role of chromatin-associated RNA processing in Early B-cell development

Award Number: F31AI188882

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 12/01/2024

PERIOD OF PERFORMANCE END DATE: 11/30/2027

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