Sheila Mansouri, Ph.D.

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SUMMARY

The research of Sheila Mansouri, Ph.D., focuses on the molecular biology and immunology of central and peripheral nerve sheath tumors. Dr. Mansouri places particular emphasis on analyzing the tumor microenvironment, using advanced spatial and single-cell technologies to gain deeper insights. Her lab integrates molecular, cellular and translational approaches to identify actionable pathways that drive tumor progression, immune suppression and treatment resistance.

Focus areas

• Glioblastoma microenvironment and the hypoxic niche. Glioblastoma (GBM) is the most aggressive brain tumor with no viable treatment options. Dr. Mansouri's lab team aims to improve the outcome of patients with GBM by studying the tumor microenvironment, with a focus on hypoxia-driven transcriptional and epigenetic states and invasive tumor behavior. By integrating spatial transcriptomics, single-cell RNA sequencing and epigenomic profiling, the lab team investigates how hypoxic niches reprogram both tumor and stromal cells to promote immune evasion, cell migration and resistance to therapy. A central goal of this work is to identify key regulators of hypoxia-induced pathways that could be targeted to disrupt protumorigenic cell-cell interactions.
• Peripheral nerve sheath tumors, malignant transformation and immune evasion. Neurofibromatosis type 1 (NF1) is a hereditary predisposition syndrome that leads to the development of a spectrum of tumors along the peripheral nerves. Dr. Mansouri's lab team investigates the full biological spectrum of peripheral nerve sheath tumors. Their research spans from benign neurofibromas, which cause severe discomfort to patients, to malignant peripheral nerve sheath tumors that are highly fatal and resistant to treatment. Using spatial and single-cell mapping, her group explores regional heterogeneity within tumors to uncover molecular pathways that drive immune suppression and malignant transformation. These efforts aim to improve risk stratification and reveal novel therapeutic vulnerabilities in malignant peripheral nerve sheath tumors and improve the quality of life for patients with benign neurofibromas.

• Immune cell infiltration and myeloid polarization. Dr. Mansouri's research identifies the molecular signals that govern immune cell infiltration and polarization within central nervous system tumors. Particular attention is given to myeloid cells, such as tumor-associated macrophages. These cells often adopt protumorigenic phenotypes. Her lab seeks to identify and target key regulators of immune cell recruitment and functional state to reprogram the tumor microenvironment and improve responses to immunotherapy.

  To translate discoveries into functional therapies, Dr. Mansouri's lab team aims to use genetically engineered mouse models alongside advanced immune cell engineering platforms. Combined with CRISPR-mRNA editing and lentiviral delivery, her team develops gene-modified macrophages designed to express therapeutic payloads, such as bispecific T cell engagers. These models are used to evaluate how modulating immune pathways influences tumor growth, immune cell infiltration and responses to immunotherapy in both syngeneic and humanized systems.

Significance to patient care

Dr. Mansouri's research aims to improve care for patients with brain and nerve tumors by studying how these tumors grow and resist treatment. She focuses on understanding the unique environment around tumors and uses advanced tools to find markers that can help predict how a tumor will behave and respond to therapy. Her work has led to new discoveries that could guide more-personalized and effective treatments. Through national and international collaborations, she is helping turn scientific insights into real-world solutions that benefit patients.

Professional highlights

• Ad-hoc reviewer, Neuro-Oncology Advances, 2025-present.
• Ad-hoc reviewer, Scientific Reports, 2025-present.
• John M. Nasseff Sr. Career Development Award in Neurologic Surgery Research, Mayo Clinic Center for Clinical and Translational Science, 2025-2028.