RESEARCH PROJECTS
Innate immunity and nucleic acid sensing are involved in an increasing number of biological processes from antiviral defences to tissue homeostasis and disease. Host antiviral factors and nucleic acid sensors play a pivotal role also in the efficacy and safety of genetic manipulation. On the other hand, the same sensors that protect us from viral infection and potentially hamper efficient gene engineering can also drive specific human autoimmune diseases when they are inappropriately activated by endogenous nucleic acids. On these premises, we study the molecular mechanisms of host-vector interplay and innate immunity in the context of gene therapies in relevant target tissues such as the central nervous system and hematopoietic stem cells and investigate these pathways in the context autoimmune, inflammatory and infectious diseases. Together, our efforts will provide insight into how nucleic acid sensing and innate immune signalling may affect efficacy and safety of gene therapy approaches in clinically relevant target cells as well as to shed light on how these same pathways contribute to autoimmune and inflammatory pathologies.
INNATE SENSING OF
GENE THERAPY VECTORS
This area of research is focused on dissecting antiviral factors and innate sensing pathways in the context of genetic engineering and has partially been funded by the European Research Council (ERC) in the context of the ImmunoStem project. Building on our past work, we are addressing vector signalling and innate immune restriction across delivery platforms and in clinically relevant target cells. These basic studies of vector-host interactions will allow modulation of identified host factors or innate sensing pathways in the context of transduction or gene editing with the goal of rendering gene engineering as inert as possible, while maximizing its efficiency.
NUCLEIC ACID IMMUNITY IN INFLAMMATORY DISEASES
Here we aim to investigate innate immunity and nucleic acid sensing in the context of inflammatory diseases such as the Aicardi-Goutières Syndrome (AGS), a rare monogenic encephalopathy in which aberrant activation of innate sensing is thought to drive disease but the precise molecular mechanisms and cell types involved remain elusive. Among other systems, we use human induced pluripotent stem cells (iPSC) harbouring AGS loss of function alleles to dissect triggers of disease in cells of the central nervous system. These studies will provide insight into the pathological cascades causing disease informing the development of targeted therapies for pathologies in which aberrant nucleic acid immunity is involved.
MOLECULAR MECHANISMS OF VIRUS-HOST INTERACTIONS
This area of research is focused on dissecting the molecular mechanisms of antiviral restriction during viral entry and the role of these factors in hampering gene delivery relying on the same cellular pathways to access the cytosol. We are also addressing regulation and additional biological roles of these antiviral factors in the context of healthy and malignant tissues.