Our laboratory investigates the dynamic immune cell interactions in the meninges and the central nervous system (CNS). Utilizing a multidisciplinary approach, our research aims to mechanistically understand how transcription factors influence the behavior and adaptation of innate lymphoid cells (ILCs) and CD4⁺ T helper cells within the CNS environment. Our objective is to pinpoint molecular pathways in ILCs and T cells that are key drivers of neuroinflammation and neurodegeneration.

Current projects:

Transcriptional regulation of CD4⁺ T cell responses in autoimmunity: This project examines the molecular underpinnings governing the developmental plasticity and tissue adaptation of CD4⁺ T helper cells. Utilizing the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis, we focus on identifying key transcription factors and their gene targets that orchestrate inflammatory responses in the CNS.

Immunoregulatory role of ILCs in the CNS: The CNS is widely recognized as an immune-privileged site that tightly regulates interactions with immune cells to protect neurons from the detrimental effects of inflammation. Nevertheless, the meninges and associated CNS bone marrow niches are populated with a diverse array of immune cells engaged in ongoing immunosurveillance. Despite this immune presence, the CNS borders serve as tightly regulated gateways, selectively controlling immune cell entry into the CNS parenchyma. Our research seeks to understand how these immunological interactions at the CNS borders translate into broader immune responses in the context of CNS autoimmunity. Our previous studies have shown that T-BET-dependent NKp46⁺ ILCs play a critical role in regulating adaptive immune responses within the meninges by affecting the optimal reactivation and stability of myelin-reactive CD4⁺ Th17 cells. This project is focused on delineating the functions and regulatory mechanisms of ILCs, particularly those within the meninges. We explore their tissue origin and how these meningeal ILCs uphold CNS integrity and their role in triggering or propagating neuroinflammatory diseases.

Deciphering the molecular basis of disrupted self-tolerance in autoimmunity: Autoimmune diseases such as multiple sclerosis manifest when the immune system erroneously attacks healthy tissues, a process often precipitated by the failure of mechanisms designed to distinguish 'self' from 'non-self.' This project seeks to unravel the molecular foundations of this breakdown in self-tolerance, focusing on T cell receptor (TCR) signaling. Our goal is to map how tissue-specific signals and inflammatory cytokines alter TCR signaling, contributing to the onset of CNS autoimmune disease.

Can we enhance anti-tumor immunity against glioblastoma multiforme (GBM)? GBM presents a critical challenge due to its aggressive nature and resistance to existing treatments. This project involves a comprehensive examination of the immune microenvironment within GBM, aiming to decode the complex interactions between immune cells, cancer cells, and neurons. Our goal is to uncover how these interactions can be manipulated to bolster anti-cancer immunity and dampen cancer-promoting inflammation, opening new avenues for therapeutic intervention.

Image