Author

Nidhi Sahni

View on Semantic Scholar

2 papers indexed here

We haven’t gathered this author’s papers yet. Follow them and we’ll fetch their work.

Not the right person? Other researchers publish under this name.

Jul 2026

Cell cycle-coupled transcriptional network regulates human B cell fate bifurcation 2257411

Antibody response quality and durability depend on activated B cells bifurcating into plasmablast (PB) or germinal center B cell (GCBC) fates. PBs are short-lived and secrete low-affinity antibodies, whereas GCBCs undergo somatic hypermutation and selection before potentially generating long-lived plasma cells that produce high-affinity antibodies. The gene regulatory networks (GRNs) governing these trajectories in human B cells remain poorly defined. We profiled in vitro—activated human B cells using time-series single-cell multi-omics (RNA/ATAC-seq) and applied machine learning to predict linkages between transcription factors (TFs), cis-regulatory elements, and target genes, building B cell state-specific GRNs. Using these GRNs, we simulated TF perturbations and tested the predicted effects using CRISPR screening in primary B cells. Simulations and experiments converged with predictions of TF activity at single-nucleotide resolution, revealing dominant and reciprocal actions of IRF4 and partners at IRF-related motifs. Single-cell perturbation analysis uncovered a reciprocal negative feedback loop that modulated B cell fate choice, involving BATF, IRF4 and BLIMP1. Additionally, we found that IRF4 and BLIMP1 co-repressed the cell cycle regulator MYC before PB differentiation. G0 lengthening accelerated the switch to a IRF4hi/BLIMP1hi state and enhanced the probability of PB specification, thereby generating a self-reinforcing regulatory module that couples cell cycle dynamics to B cell fate choice. This work establishes a generalizable framework for assembling and testing GRNs in the context of immune cell fate decisions. Applying this approach to human B cells revealed previously unreported feedback loops that link cell division to fate specification. These findings have implications for strategies to modulate antibody responses in humans. Cancer Research Institute (#4185) ; NIAID (#5T32AI089443) Immune Response Regulation: Molecular Mechanisms (IRM)

Nicholas A. Pease, Jingyu Fan, S. Keshari et al. · Journal of Immunology · 0 citations

Open access Aug 2026

Suppression of EGFR signaling and drug-induced potentiation are widespread features of oncogenic RTK fusions.

Regulation of cancer cells by their environment contributes to tumorigenesis and drug response, though the extent to which the oncogenic state can alter a cell's perception of its environment is not clear. EML4-ALK is a receptor tyrosine kinase (RTK) fusion oncoprotein that suppresses transmembrane EGFR signaling in cancer cells. ALK inhibition restores signaling through EGFR, thereby promoting survival and drug tolerance. Here, we tested whether such modulation of EGFR activity was common among other RTK fusions, which collectively are found in ~5% of all cancers. Using live- and fixed-cell microscopy in isogenic and patient-derived cell lines, we found that a wide variety of RTK fusions suppress transmembrane EGFR, through mechanisms that include the sequestration of the adaptor protein Grb2. Targeted therapies rapidly released Grb2 from sequestration and potentiated EGFR. Synthetic optogenetic analogs of RTK fusions confirmed that cytoplasmic sequestration of Grb2 was sufficient to suppress perception of extracellular EGF and could do so without driving signaling from the synthetic fusion itself, demonstrating that fusion signaling and suppression of EGFR signaling could be functionally decoupled. Our study uncovers that a large number of RTK fusions simultaneously act as both activators and suppressors of signaling, the mechanisms of which could be exploited for biomimetic therapies that enhance cell killing and suppress drug tolerance.

Y. Gao, D. Gonzalez-Martinez, Sofia Wissert et al. · Proceedings of the National... · 0 citations