COLife Immunology & Inflammation Research Groups
Get to know the Research Groups at COLife Institutes. This week we are featuring COLife Immunology & Inflammation Research Groups.
Helena Soares Lab – Human Immunobiology and Pathogenesis
The Human Immunobiology and Pathogenesis lab studies the variation of the immune response throughout human lifespan: from before birth to adulthood and aging, including our particular interest in addressing why female and male immune responses are different. Using the ultimate disease model: the Human, we aim at understanding tissue- and cell-specific factors controlling the induction of protective versus pathogenic immunity in order to manipulate them therapeutically in vaccine design and to treat autoimmune diseases. Central to our research is the molecular access to human tissues and a mechanism-driven development of biologicals at the interface of immunology, clinical research and biotechnology.
Henrique Veiga-Fernandes Lab – Immunophysiology
The Immunophysiology lab explores the role of cross-talk between neurons and the immune system in the prevention and resolution of disease. To that end, the team mainly focuses on mucosal barriers, such as the intestine and the lung. These organs are in permanent contact with the external environment and have a complex and dense network of neuronal and immune cells. This combination of features makes these organs an optimal site to reveal how the neural and immune systems work together to preserve health.
Using this approach, the lab has recently revealed a surprising role of the neural network that surrounds these organs: immune regulation. The team discovered that while the immune system is the one that actively fights infection, the neurons are the ones that are in charge of detecting the invasion and setting the immune response in motion. These findings may have tremendous potential in the design of novel therapeutic approaches to disease as they pinpoint new selective targets that can be harnessed in allergy, inflammation, obesity and cancer.
Rita Fior Lab – Cancer Development & Innate Immune Evasion
The Cancer Development & Innate Immune Evasion lab pursues two main research objectives:
The first is to develop tools for personalised medicine. Despite advances in targeted cancer treatments, we still lack methods to predict how a specific cancer in a specific patient will respond to a given therapy. Consequently, patients go through rounds of trial-and-error, to find the best treatment, often subjected to unnecessary toxicity. The lab is developing a system where patient-derived tumour-samples are implanted into zebrafish larvae. These “avatars” are used as sensors for cancer behaviour and personalised therapy screening (Fior et al, 2017). Early results are very promising and the team is currently pursuing this venue of research in various cancer types.
The second goal of the lab is to study how tumours evade the immune system. To thrive, tumour cells employ mechanisms that circumvent the immune response. By combining live imaging, genetic and chemical tools, the team is studying the process of innate immune evasion and intra-tumoral clonal interactions using the zebrafish-larvae xenograft model. The researchers believe that understanding the process of innate immune rejection/evasion may lead to new avenues of anti-cancer therapies to be combined with immune-checkpoint blockers, increasing efficacy rates and taking immunotherapy to more patients.
Cristina João Lab – Myeloma Lymphoma
The experimental work of the Myeloma Lymphoma Research Programme includes a broad spectrum of research activity, where clinical haematologists from the Haemato-Oncology Unit and non-clinical researchers from Champalimaud Research, work together to expand their knowledge of the biology of mature lymphoid neoplasms and their treatment.
Currently, we have several experimental research projects in collaboration with research groups including the Systems Oncology Group, the Computational Clinical Imaging Group and the Cancer Development and Innate Immune Evasion Group. These projects address questions such as mechanisms of progression of Multiple Myeloma, novel methods of evaluating bone disease, minimal residual disease in multiple myeloma and tailored therapy based on “in vitro” drug sensitivity evaluation.
Markus Maeurer Lab – Immunotherapy/ImmunoSurgery
The Immunotherapy/ImmunoSurgery lab is currently setting up a research and clinical structure to offer cellular treatment for cancer patients with a strong pre-clinical and clinical interaction to: (i) better understand the tumour-host relationship (ii) map each patient’s individual mutational burden and the immunological ‘texture’ of the patient’s immune responses (‘adaptomics’ ), and (iii) identify biologically relevant immunological strategies for improved cellular therapy concepts in the treatment of patients with cancer.
Jocelyne Demengeot Lab – Lymphocyte Physiology
The Lymphocyte Physiologylab is interested in the properties of the immune system that guarantee tissue integrity as well as tolerance to commensals and food antigens while maintaining the ability to mount efficient responses to infectious agents and some tumours. Rooted in this thematic is also the biological puzzle of phenotypic heterogeneity, the challenge of personalised medicine.
The lab approach the cellular and molecular bases of immune regulation through the analysis of various mouse models, notably of spontaneous or induced autoimmune and immuno-pathological inflammation.
Closer to the clinic, they interrogate the biological basis of the most extreme manifestations in autoimmune diseases and of the variable efficacy of immunotherapies.
Miguel Soares Lab – Inflammation
The major aim of Inflammation lab is to identify and characterize the stress and damage responses that conferring tissue damage control and establishing disease tolerance to infections. The central hypothesis tested is that there is a functional interplay between immune-driven resistance mechanisms and stress and damage responses acting in parenchyma tissues, which limits the pathogenic effects of infection. Understanding the mechanisms governing this functional interplay should be transformative in our understanding of host microbial interactions, with direct impact on the treatment of infectious diseases.
The lab has recently discover that the loss of a specific molecule may explain how primates evolved to be able to resist to bacterial infections leading to sepsis. They have shown that, in mice,the absence of this molecule (the α-Gal glycan) from the antibodies structure increases the ability to the same antibody to kill bacteria. This evolutionary advantage emerged with a cost, the reproductive decline. These findings shed light on key aspects of hominid evolution and reveal new mechanisms that confer resistance against sepsis, crucial to understand and fight the disease.
Vera Martins Lab – Lymphocyte Development and Leukemogenesis
Research in the Lymphocyte development and Leukemogenesis Lab focuses on T lymphocyte development, both under steady state, physiological conditions, as well as in leukemia. T lymphocyte development occurs mostly in the thymus from progenitors of bone marrow origin in a process that involves high cellular turnover. The research team found that thymus turnover is regulated by cell competition. Specifically, the seeding of the thymus by ‘young’ hematopoietic precursors (with a short dwell time in the thymus) led to the clearance of the ‘old’ precursors (residing for longer in the thymus).
Importantly, cell competition is not cell autonomous, i.e., it is the presence of the young that induce the clearing of the old. Consistently, when no progenitors seed the thymus, i.e., if no cell competition took place, old precursors persisted in the thymus, self-renewed, and for some time gave rise to T lymphocytes. In other words, autonomously maintained thymus function. Nevertheless, while apparently beneficial for a short period, prolonged thymus autonomy led to aggressive T cell acute lymphoblastic leukemia with strong similarities with the human disease. The lab focuses on the identification of the cellular and molecular mechanisms governing cell competition in normal thymus turnover, and on the changes associated with the malignant transformation of T lymphocyte precursors as a consequence of impaired cell competition.
Ana Espada de Sousa Lab – Human Immunodeficiency & Immune Reconstitution
The Human Immunodeficiency & Immune Reconstitution lab investigates immune regulation and human T-cell homeostasis with the ultimate goal of identifying new strategies for immunological reconstitution and targets for immune-based therapies. An important part of the lab research effort is centered on HIV/AIDS immunopathogenesis, mainly through the study of HIV-2 infection, a naturally attenuated form of HIV disease, and on Inborn Errors of Immunity leading to Human Immunodeficiency.
Bruno Silva-Santos Lab – Immuno-Biology & Immuno-Oncology
The Immuno-Biology & Immuno-Oncology lab is interested in the pleiotropic roles of immune cells in tissue (patho)physiology. Within their major research line of Immuno-Oncology, the lab study T lymphocytes and macrophages, using in vitro and in vivo models, for the identification of molecular mechanisms involved in their differentiation, activation and functions in cancer, with the ultimate goal of designing novel immunotherapy strategies.
In a more recent area – Neuroimmunology – the lab explores the crosstalk between the immune system, particularly T cells that populate the meninges, and the brain – either in health (cognition) or in disease (neurodegeneration).
Joana Neves Lab – Ageing & Tissue Repair | Immune Modulation in Tissue Repair
The Ageing & Tissue Repair lab’s central interest is the exploration of the tissue repair processes that have evolved to heal damaged organs to improve regenerative success in older individuals. The lab uses skeletal muscle regeneration as a paradigm of tissue repair to understand the molecular and cellular basis of the immune modulatory component of tissue regeneration and how its dysregulation in ageing and disease can be targeted to optimize stem cell-based therapies. The goal is to identify pathways that are used by immune cells to modulate the inflammatory tone of the tissue environment, with the goal of identifying new molecules with immune modulatory properties and therapeutic potential in regenerative medicine applied to old patients.
Luís Graça Lab – Lymphocyte Regulation
The Lymphocyte Regulation lab studies mechanisms underlying induction and maintenance of immune tolerance. In other words, the lab research methods to alter the balance of the immune response: reducing its action when the immune system is causing a disease, such as allergy, autoimmunity, and transplant rejection; or enhancing the immune response to vaccines or infection. The lab is especially interested in defining the functional properties of lymphocytes that can promote immune tolerance by suppressing pathogenic immune responses.
Marc Veldhoen Lab – Immune Regulation
The Immune Regulation lab is interested in how T cells are activated and differentiate, and how tissue resident T-cells are generated, maintained and activated at the epithelial barrier, especially in the small intestine. The aim is to understand the cellular and molecular cues, which result in epithelial T-cell generation and activation.