As befits a technological area, the Advanced Cell Models – Disease Microenvironments and Therapeutic Responses Laboratory is integrated into the Animal Cell Technology Unit, where a number of knowledge competencies are balanced.
The simplistic view of disease revolving around a target cell in its tissue has been challenged by the recognition of the role of the heterogeneous and dynamically evolving disease microenvironment in pathogenesis and therapeutic response. Treatment strategies that target or modify the abnormal disease microenvironment are currently a trend. As such, a deeper understanding of the mechanisms that drive the formation, maintenance, and progression of the disease microenvironment is necessary.
At the Advanced Cell Models Lab, our research is mostly translational, in the areas of cancer and neurological diseases. Our primary objective is to identify new molecular players in dynamic disease microenvironments that may be involved in disease progression and responses to therapy, to uncover novel therapeutic targets and predictive biomarkers of the response to treatment.
To better understand the mechanisms underlying the maintenance of disease microenvironments, we are developing innovative human 3D cell models. We employ advanced cell culture techniques such as 3D culture, co-culture, cell immobilization, and bioprinting, alongside sophisticated systems like microfluidics and bioreactors, to cultivate human stem cells and other cells derived from patients. These models accurately represent the various cell types contributing to the microenvironment and replicate the dynamics of both cellular and extracellular spaces without the confounding effects of heterologous ECM and soluble factors. By integrating cutting-edge techniques such as confocal imaging, transcriptomics, proteomics, and glycomics—including single-cell omics—we can observe and analyze the dynamic modulation of specific cell microenvironments over time or in response to therapeutic interventions.
Our group has pioneered cell-based strategies to tackle challenges in the imminent areas of cancer immunotherapies and viral vector-based gene therapies. We have been progressively focusing on chronic inflammation and myeloid cell-driven immunosuppressive microenvironments. We are developing complex cell models and generating biological knowledge along two central research lines:
1. Macrophage-tumor cell crosstalk within the tumor microenvironment in immunosuppression and resistance to immunomodulatory therapies;
2. Neuron-glia crosstalk in neuroinflammation in the central nervous system (CNS) and innate immune response to viral vector-based gene therapies.
A nossa investigação é essencialmente translacional, centrada no estudo do papel do microambiente imune inato na progressão de doenças neurológicas e tumores sólidos, bem como na resposta a terapias avançadas. Para responder a estas questões, recorremos a modelos celulares de doença, baseados em células estaminais e/ou outras células derivadas de pacientes, explorando estratégias de cultura celular tridimensional. Combinamos metodologias de biologia celular e ferramentas omics para caracterizar os modelos desenvolvidos e identificar novas moléculas envolvidas na progressão das doenças e na resposta aos agentes terapêuticos.
