Srivastava Lab · The Wistar Institute · Philadelphia
One exon. One cell. One decision at a time.
Splicing is where a gene becomes an isoform — quietly rewritten in both drug-resistant cancer and hyperactivated autoimmune disease. The Srivastava Lab builds the technology and the computation to read those decisions one cell, one isoform at a time.
Why we exist
Biology is currently measured at gene-level resolution, which collapses roughly twenty thousand protein-coding genes into a single number each and erases the more than two hundred thousand isoforms those genes actually produce. The choices hidden inside that collapse — which exon is included, which 3′ end is used, which regulatory feature is decorated — are exactly the choices that drive drug-resistant states in cancer and hyperactivated states in autoimmune disease. The Srivastava Lab builds the technology and the computation needed to read that regulation at isoform resolution, in individual cells, before the protein is ever made.
Research pillars
Four tightly coupled efforts: a benchtop single-cell platform, a long-read isoform quantification pipeline, cross-platform integration, and co-equal biological programs in cancer and autoimmunity.
Microfluidics-free benchtop single-cell RNA-seq. PIP-seq capture + Oxford Nanopore sequencing on any standard lab bench, extending naturally to chromatin via PIP-ATAC.
Spacer-anchored barcode recovery, junction-based read assignment, EM-based multi-mapping resolution, and principled isoform × cell count matrices from raw Nanopore signal.
Two-layer annotation strategies that transfer cell identity from short-read atlases to long-read BenchDrop-seq data, and multimodal frameworks that align RNA, chromatin, and isoform state per cell.
Two co-equal biological programs: drug-tolerant persister states in NRAS-mutant melanoma, and splicing rewiring of immune cell fate in multiple sclerosis and EBV-driven dysregulation.
Srivastava Lab tools
Open-source platforms and pipelines developed independently in the lab since September 2023. Every method ships with documented, reproducible code.
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