Biology subjects

Ganjoo, K. N.

Publications and source records attributed to Ganjoo, K. N..

3 recordsLinked to original sources

bioRxiv2025

Multidimensional Single-Cell Transcriptomic Profiling of Uterine Leiomyosarcomas Identifies Molecular Subtypes with Distinct Therapeutic Vulnerabilities

Uterine leiomyosarcoma (ULMS) is an orphan disease that frequently recurs and metastasizes, with patients undergoing multiple lines of chemotherapy due to lack of effective therapeutic targets. To address this gap, we used single-cell RNA sequencing and spatial transcriptomic analysis to comprehensively profile ULMS. We uncovered multiple states of tumor cells, including tumor cells with mesenchyme-like features, ischemic tumor cells defined by a MYC program, inflammatory tumor cells with active interferon signaling, and stem cell-like hormone receptor-positive cells. The inferred spatial correlates of these tumor cell states demonstrated unique localization patterns. By correlating these signatures to bulk RNA sequencing data, we demonstrate the relevance of these findings to clinical outcomes. Finally, using the single-cell integration and drug response prediction algorithm (scIDUC), we propose drug predictions that may target specific tumor states. Our findings suggest new avenues for further exploration of individualized and multifaceted therapeutic strategies to treat ULMS.

cancer biology↗

bioRxiv2025

SCAN-ACT: Adoptive T Cell Therapy Target Discovery Through Single-Cell Transcriptomics

The FDA approval of T cell receptor-engineered T cells (TCR-T) for synovial sarcoma demonstrates the potential for adoptive T cell therapies (ACTs) in solid tumors. However, the paucity of tumor-specific targets without expression in normal tissues remains a major bottleneck, especially in rare cancer subtypes. Here, we present a comprehensive computational pipeline called SCAN-ACT that leverages single cell RNA sequencing and multi-omics data from tumor and normal tissues to nominate and prioritize targets for both chimeric antigen receptor (CAR)- and TCR-T cells. For surface membrane targets, SCAN-ACT proposes target pairs for bispecific Boolean logic-gated CAR T cells. For peptide-MHC targets, SCAN-ACT proposes intracellular peptides bound to a diverse set of human leukocyte antigens. We applied the SCAN-ACT pipeline to soft tissue sarcoma (STS), analyzing 986,749 single cells to identify and prioritize 395 monospecific CAR-T targets, 14,192 bispecific CAR-T targets, and 5,020 peptide-MHC targets for TCR-T cells. Selected targets were validated experimentally by protein expression and for peptide-MHC binding. Proposed targets and target pairs reflected the mesenchymal, neuronal, and hematopoietic ontogeny of STS. This work provides a robust data repository along with a web-based and user-friendly set of analysis tools to accelerate ACT development for solid tumors.

cancer biology↗

bioRxiv2022

Interactions in CSF1-driven Tenosynovial Giant Cell Tumors

The majority of cells in Tenosynovial Giant Cell Tumor (TGCT) are macrophages responding to CSF1 that is overproduced by a small number of neoplastic cells with a chromosomal translocation involving the CSF1 gene. Treatment with inhibitors of the CSF1 pathway has been clinically effective. An autocrine loop was postulated where the neoplastic cells are stimulated through the CSF1 receptor (CSF1R) expressed on their surface. Here we show that the neoplastic cells themselves do not express CSF1R and therefore may be unaffected by current therapies. We identified a new marker for synoviocytes, GFPT2, that highlights the tumor cells in TCGT and is associated with activation of the YAP1/TAZ pathway. The neoplastic cells in TGCT are highly similar non-neoplastic synoviocytes. Finally, we provide molecular support for the osteoclast-like features of the giant cells in TGCT that correlate with the destructive effects of TGCT on bone.

cancer biology↗