Elaheh Hashemi

All Publications

• MAPK-driven glioma progression and reprogramming of the tumor-associated immune response. Neuro-oncology Hashemi, E., Akshaya, R. L., Wang, L., Bergland, S., Piyadasa, H., Ranek, J. S., Voong, V., Kshirsagar, A., Shai, A., Oberlton, B., Kumar, A., Berger, M. S., Chang, E. F., Oldham, M. C., Prins, R. M., Bendall, S. C., Angelo, M., Hervey-Jumper, S. L., Okada, H., Diaz, A., Phillips, J. J. 2026

  Abstract

  In brain tumors, the immunosuppressive microenvironment leads to tumor aggressiveness and immunotherapy resistance. To identify factors that regulate the glioma immune landscape, we took advantage of the disease trajectory of the MAPK-driven glioma, pleomorphic xanthoastrocytoma (PXA), which evolves from an immune-rich low-grade tumor to an aggressive glioma.Using a multiomics approach that included single-nucleus RNA sequencing (snRNA-seq), spatial transcriptomics, and spatial proteomics, a cohort of 38 tumors, including 10 longitudinal pairs, was profiled.Tumor progression was associated with transition to a more proliferative progenitor state and increased hypoxia. Hypoxic reprogramming of the immune landscape included increased TGF-β signaling and altered chemokine signaling, including decreased CXCL14 and CXCL16-CXCR6 signaling important in immune cell recruitment and activation. The resulting immune landscape was spatially reorganized with reduced HLA Class II expression, reduced CD8+ and CD4⁺ T cells, and dominated by immunosuppressive myeloid cells.Hypoxia and chemokine signaling emerged as key components of the glioma-immune landscape that evolve with tumor progression. These findings identify potential therapeutic opportunities in PXA, and they argue that optimal immunomodulatory strategies in glioma will differ along the disease trajectory.

  View details for DOI 10.1093/neuonc/noag147

  View details for PubMedID 42377256

• Paxillin in mechanosensitive spatial control of lung endothelial cell regeneration. NPJ Regenerative medicine Mammoto, T., Kyi, P., Scheer, M., Hunyenyiwa, T., Hashemi, E., Ma, X., Turner, C. E., Lin, C. W., Malarkannan, S., Mammoto, A. 2026

  Abstract

  Mechanical forces altered after unilateral pneumonectomy (PNX) control post-PNX lung growth. Here, we demonstrate that post-PNX endothelial regeneration is stimulated at the peripheral region of the mouse lung, requiring the focal adhesion (FA) protein, paxillin, while inhibition of mechanical tension attenuates the effects. Paxillin mediates stretching-induced YAP1-TEAD1 signaling, which stimulates GATA2 activity on angiogenic factor angiopoietin-2 (ANGPT2) transcription in endothelial cells (ECs), dictating post-PNX endothelial regeneration at the peripheral region. Deleting endothelial paxillin suppresses expression of GATA2 in the specific EC subtype, capillary type 1 ECs (CAP1s) following PNX. Extracellular matrix protein, collagen VI that impacts cell mechanical responses is expressed more at the peripheral region in the post-PNX mouse lungs, which drives paxillin expression, leading to EC regeneration. Mechanosensitive paxillin signaling in ECs mediates spatial control of post-PNX endothelial regeneration.

  View details for DOI 10.1038/s41536-026-00476-9

  View details for PubMedID 42151171

• Transcriptomic diversity of innate lymphoid cells in human lymph nodes compared to BM and spleen. Communications biology Hashemi, E., McCarthy, C., Rao, S., Malarkannan, S. 2024; 7 (1): 769

  Abstract

  Innate lymphoid cells (ILCs) are largely tissue-resident, mostly described within the mucosal tissues. However, their presence and functions in the human draining lymph nodes (LNs) are unknown. Our study unravels the tissue-specific transcriptional profiles of 47,287 CD127+ ILCs within the human abdominal and thoracic LNs. LNs contain a higher frequency of CD127+ ILCs than in BM or spleen. We define independent stages of ILC development, including EILP and pILC in the BM. These progenitors exist in LNs in addition to naïve ILCs (nILCs) that can differentiate into mature ILCs. We define three ILC1 and four ILC3 sub-clusters in the LNs. ILC1 and ILC3 subsets have clusters with high heat shock protein-encoding genes. We identify previously unrecognized regulons, including the BACH2 family for ILC1 and the ATF family for ILC3. Our study is the comprehensive characterization of ILCs in LNs, providing an in-depth understanding of ILC-mediated immunity in humans.

  View details for DOI 10.1038/s42003-024-06450-9

  View details for PubMedID 38918571

  View details for PubMedCentralID PMC11199704

• Tissue-Resident NK Cells: Development, Maturation, and Clinical Relevance. Cancers Hashemi, E., Malarkannan, S. 2020; 12 (6)

  Abstract

  Natural killer (NK) cells belong to type 1 innate lymphoid cells (ILC1) and are essential in killing infected or transformed cells. NK cells mediate their effector functions using non-clonotypic germ-line-encoded activation receptors. The utilization of non-polymorphic and conserved activating receptors promoted the conceptual dogma that NK cells are homogeneous with limited but focused immune functions. However, emerging studies reveal that NK cells are highly heterogeneous with divergent immune functions. A distinct combination of several activation and inhibitory receptors form a diverse array of NK cell subsets in both humans and mice. Importantly, one of the central factors that determine NK cell heterogeneity and their divergent functions is their tissue residency. Decades of studies provided strong support that NK cells develop in the bone marrow. However, evolving evidence supports the notion that NK cells also develop and differentiate in tissues. Here, we summarize the molecular basis, phenotypic signatures, and functions of tissue-resident NK cells and compare them with conventional NK cells.

  View details for DOI 10.3390/cancers12061553

  View details for PubMedID 32545516

  View details for PubMedCentralID PMC7352973