Uttiya Basu
Columbia University, NY·Microbiology & Immunology
The immune system can make antibodies against an almost unlimited range of invaders because B cells deliberately cut and mutate their own antibody genes. Three processes do this.
- Fields
Microbiology & Immunology
Genetics
Biochemistry
- Topics
B cells
antibody diversification
VDJ recombination
- Grants
- 4 known grants, through Nov 2029
What they work on
- Test whether B cell development can be rescued in RNA exosome-deficient mice, and whether VDJ-carRNAs, chromatin-associated RNAs from the IgH locus, control VDJ recombination efficiency by the RAG enzymes.
- Determine which RNA helicases, enzymes that unwind RNA and assist the exosome, are required for B cell development and VDJ recombination, using cell lines and mouse models.
- Test whether YTHDC1, a protein that reads the m6A RNA tag, drives class switch recombination and somatic hypermutation, using CRISPR/Cas9 genome and RNA editing, STORM microscopy and a cell-based mutation assay.
- Define how lncRNA-expressing loci organize the IgH topologically associating domain and control recombination, using lncRNA-deficient mice, protein pulldowns, and Hi-C and 4C-seq chromosome maps.
- Determine how the RNA exosome and CTCF-binding element RNAs (cbeRNAs) guide AID to mutate DNA and stabilize 3D genome structure, using exosome-deficient mice and newly identified exosome cofactors.
More about the research
VDJ recombination assembles gene pieces using the RAG1 and RAG2 enzymes. Class switch recombination (CSR) swaps the antibody type. Somatic hypermutation (SHM) adds point mutations. CSR and SHM both depend on activation-induced deaminase (AID), an enzyme that alters DNA. These programmed DNA breaks are risky. When they are poorly controlled, they cause immune deficiencies or lead to leukemias and lymphomas. All of these processes happen alongside the production of noncoding RNAs (ncRNAs), RNA molecules that do not encode proteins. The lab studies how these RNAs, the machinery that processes and modifies them, and the 3D folding of the genome steer DNA breaks to the correct places.
Why it matters
When antibody gene editing goes wrong, B cells can acquire cancer-causing chromosome rearrangements. These are linked to diffuse large B-cell lymphoma (DLBCL) and multiple myeloma. Defects in this editing also underlie immune deficiencies such as THES syndrome, Hyper-IgM syndrome type 2 and IgA deficiency. Understanding how RNAs and RNA-processing complexes guide DNA breaks could clarify how these diseases arise. It may also inform therapies, including for exosome-linked neurodegenerative disorders.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
The role of N6-methyladenosine RNA modification in programmed and aberrant DNA mutagenesis in B cells
NIH · Sep 2020 – Nov 2029
RNA associated mechanisms for antigen receptor gene diversification during immature B cell development
NIH · Jun 2024 – Apr 2029
Long noncoding RNA expressing genomic elements that control antibody diversification and chromosomal integrity in B cells
NIH · Dec 2017 – Dec 2027
Closest labs
Yu Zhang
Michigan State University, MI·Microbiology & Immunology
Test whether cohesin-driven chromatin loop extrusion, in which DNA is pulled through cohesin to form loops, is required to bring distant V segments together with DJ segments for recombination at the IgH locus.
Marcus Clark
University of Chicago, IL·Microbiology & Immunology
Define BRWD1's functions in germinal center B cells and test whether they depend on its conversion of static cohesin to dynamic, DNA-looping cohesin, using Brwd1 deletion.
Todd Waldman
Georgetown University, DC·Genetics
Determine how STAG2-regulated chromatin loops, especially those anchored by CTCF and H3K27me3, control nearby gene expression in glioblastoma cells and tumors, using Hi-C, RNA-seq and the HiCorr/DeepLoop loop-detection pipelines.
The school
Columbia University: 89 labs on PI Pages, $1.4B a year on research, 625 research doctorates a year.
Reach out
A start for your email. Fill in the brackets.