Tommas Ellender associate professor

Research Tommas Ellender

Research team

Expertise

The overall aim of our group is to understand how neuronal circuits form early in development, as well as the processes that lead to malfunction or degeneration of these circuits later in life. Research is conducted in both humans and other model species using a variety of methods including EEG measurements, in vitro and in vivo electrophysiology, HPLC and other molecular biology techniques. The focus is on the brain areas of the hippocampus, cortex as well as the basal ganglia and their role in cognition and motor control.

Alliance for multidimensional and multidisciplinary neuroscience (µNEURO). 01/01/2026 - 31/12/2031

Abstract

Owing to their high spatiotemporal resolution and non-invasive nature, (bio)medical imaging technologies have become key to understanding the complex structure and function of the nervous system in health and disease. Recognizing this unique potential, μNEURO has assembled the expertise of eight complementary research teams from three different faculties, capitalizing on advanced neuro-imaging tools across scales and model systems to accelerate high-impact fundamental and clinical neuro-research. Building on the multidisciplinary collaboration that has been successfully established since its inception (2020-2025), μNEURO (2026-2031) now intends to integrate and consolidate the synergy between its members to become an international focal point for true multidimensional neuroscience. Technologically, we envision enriching spatiotemporally resolved multimodal imaging datasets (advanced microscopy, MRI, PET, SPECT, CT) with functional read-outs (fMRI, EEG, MEG, electrophysiology, behaviour and clinical evaluation) and a molecular context (e.g., fluid biomarkers, genetic models, spatial omics) to achieve unprecedented insight into the nervous system and mechanisms of disease. Biologically, μNEURO spans a variety of neurological disorders including neurodegeneration, movement disorders, spinal cord and traumatic brain injury, glioblastoma and peripheral neuropathies, which are investigated in a variety of complementary model systems ranging from healthy control and patient-derived organoids and assembloids to fruit flies, rodents, and humans. With close collaboration between fundamental and preclinical research teams, method developers, and clinical departments at the University Hospital Antwerp (UZA), μNEURO effectively encompasses a fully translational platform for bench-to-bedside research. Now that we have intensified the interaction, in the next phase, μNEURO intends to formalize the integration by securing additional large-scale international research projects, by promoting the interaction between its members and core facilities and by fuelling high-risk-high-gain research within the hub and beyond. This way, μNEURO will foster breakthroughs for the neuroscience community. In addition, by focusing on technological and biological innovations that will streamline the translational pipeline for discovery and validation of novel biomarkers and therapeutic compounds, μNEURO aims to generate a long-term societal impact on the growing burden of rare and common diseases of the nervous system, connecting to key research priorities of the University of Antwerp, Belgium, and Europe.

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  • Research Project

Network-based computational drug repurposing for the treatment of KCNQ2-encephalopathy. 01/11/2024 - 31/10/2026

Abstract

Developmental and epileptic encephalopathy (DEE) caused by pathogenic variants in the KCNQ2 gene is a severe, early-onset neurological disorder characterised by neonatal seizures and developmental delay. Although seizures can be controlled in many KCNQ2-DEE patients with anti-seizure medication, there are no treatments that address the developmental problems. As a result, these children require intensive care for the rest of their lives. Given the slow and expensive nature of the drug discovery process, the prospects of providing safe and effective treatments for KCNQ2-DEE patients in a short term remain low. In this project, I will combine state-of-the-art in vitro brain organoids with transcriptomic technology, innovative electrophysiological readout systems and a computational prediction strategy to develop a drug screening platform to repurpose well-characterised FDA-approved drugs. This approach will provide unprecedented insight into the underlying molecular pathology of KCNQ2-DEE together with the potential to identify novel drug candidates for this disorder. If successful, the drug screening platform can be extended to other neurodevelopmental disorders for drug compound identification.

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  • Research Project

Investigating the role of the neuromodulator histamine and the development of the bed nucleus of the stria terminalis (BNST) generating novel insights in Tourette's syndrome and OCD. 01/02/2024 - 31/01/2026

Abstract

While physiological levels of histamine in the developing brain are tightly controlled, genetic mutations or inflammation can result in pathological dysregulation of histaminergic transmission. Dysregulation of histamine is associated with neurodevelopmental disorders such as Tourette's syndrome (TS) and obsessive-compulsive disorder (OCD). Alongside a high heritability, environmental risk factors for Tourette's syndrome are predominantly pre- and perinatal, highlighting early neurodevelopment as crucial in its pathophysiology. Current management is based around using atypical antipsychotics. These are often poorly tolerated with a high burden of metabolic side effects. Therefore, an urgent need to identify new targets for treatment is needed. The mechanisms by which histamine levels control brain development are only just beginning to be understood. Although classically thought of as developmental disorders of the motor circuits of the brain (e.g. the basal ganglia), both disorders show a strong social component where both stress and anxiety can initiate as well as exacerbate symptoms, with an underlying reason remaining largely unknown. In this project, we aim to employ a mouse model of TS/OCD through pharmacological modulation of histamine levels at both pre- and postnatal periods and assess the impact of histamine on the development of a key circuit in the regulation of stress and anxiety responses – the bed nucleus of stria terminal or BNST. Although the focus will be on understanding the impact on developing neurons and neural circuits, we will include assessments of the inflammatory state of the brain and establish whether histamine deficiency leaves the developing brain more vulnerable to proinflammatory insults by altering microglial activation. This will form the basis of further research on whether early intervention using histaminergic drugs or immunomodulatory therapies such as small molecule inhibitors or monoclonal antibodies could have therapeutic benefits on TS.

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  • Research Project

Unraveling the role and contribution of neurons and microglia to the neurodevelopmental problems seen in children with KCNQ3 gain-of-function encephalopathy. 01/02/2023 - 31/01/2025

Abstract

Kv7.2 and Kv7.3 subunits, encoded by KCNQ2 and KCNQ3, form homo- or hetero-tetrameric voltage-gated potassium channels (Kv7 channel). Kv7 channels expressed in neurons produce a well characterized M-current that is a critical regulator of neuronal excitability by dampening repetitive firing. Gain-of-function (GoF) variants in KCNQ2 and KCNQ3 lead to severe early-onset neurodevelopmental disorders (KCNQ2- and KCNQ3-GoF-Encephalopathy). However, autism spectrum disorder (ASD) is a much more prominent feature in KCNQ3-GoF-Encephalopathy. This suggests for a Kv7.3 unique function during neurodevelopment. Interestingly, single nuclei RNA sequencing databases have revealed that KCNQ3 is the only KCNQ gene that is highly expressed in microglia in the human brain. Given the emerging evidence that microglia dysfunction is involved in the development of NDD and ASD, we hypothesize that KCNQ3-GoF variants affect microglia function which contributes to the already dysfunctional neuronal network. In this project, I will build a human tripartite neuronal-microglia model (excitatory neurons, inhibitory neurons and microglia) derived from induced pluripotent stem cells that carry KCNQ-GoF variants, as well as control lines. With this model I will (i) investigate the function of Kv7.3 in microglia and (ii) unravel the contribution of each cell type to KCNQ3-GoF-Encephalopthy. Furthermore, this model will be used as a screening platform to perform a proof-of-concept study for RNA interference using antisense oligonucleotides as a targeted treatment strategy for KCNQ3-GoF-Encephalopathy. When successful, this approach could be extended to other types of neurodevelopmental disorders and drug screenings.

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  • Research Project

Elucidating the roles for embryonic neural progenitor diversity in the formation and function of mature striatal neuronal circuits. 01/01/2023 - 31/12/2026

Abstract

Specialised cells in the embryonic brain, termed neural progenitors, give rise to all mature neurons, including those found in the striatum, a brain region critical in controlling our movements and many cognitive behaviours. These progenitor cells come in many shapes and sizes, and it remains unclear why so many different types exist, and importantly how they relate to the neurons and neural circuits found in the adult brain. This is a fundamental question and important also from a clinical perspective as alterations in embryonic progenitors are implicated in the emergence of various neurological disorders. This proposal capitalises on our ability to label distinct embryonic progenitor types and all their neurons, and firstly aims to elucidate the genes and proteins that are expressed in these mature neurons as to facilitate their classification, as well to trace their connections with other neurons in the brain. Secondly, it aims to characterise the electrical properties of these connections with a focus on those coming from an important brain region, named the thalamus, and through manipulations and behavioural studies reveal how these progenitor-derived neural circuits control movement and cognition. Together, this will provide fundamental insights into the origin of the brain's complexity, by uncovering how embryonic progenitors shape the functional identity of mature striatal neurons and opens avenues for future studies of their roles in striatal disorders.

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  • Research Project

Het begrijpen van hersencircuits vanuit de oorsprong van neuronale embryonale progenitors. 01/10/2022 - 30/09/2026

Abstract

The brain's ability to process information and guide behaviour is reliant on diverse neurons forming complex neuronal circuits. In this PhD project proposal, we set out to explore how such diversity in neurons and synaptic circuits arises with a focus on embryonic progenitor origin and using mouse as a model organism. Recently data from my lab and others suggest that key aspects of neuronal identity and synaptic specificity in both cortex and striatum are controlled by their embryonic progenitor origin. In this proposal we will explore this further and focus on the striatum, but the tools and approaches generated will be universally applicable. The PhD project proposal has four main Objectives. Firstly, we will use RNA sequencing approaches to genetically parse the different embryonic progenitors that generate striatal spiny projection neurons (SPNs) and generate tools for their fate mapping from embryo to adulthood. Secondly, we will use a variety of techniques on adult SPNs to determine what 'types' of neurons arise from different progenitor pools. Thirdly, we will use novel viral tracing approaches to observe the synaptic integration of striatal SPNs within larger brain circuits. Lastly, we will reveal the molecular recognition systems that different embryonic progenitor-derived SPNs employ to achieve synapse specificity within these larger circuits. Together they will provide new insights how the vast complexity of neurons and circuits in the striatum arises and open avenues for future study of the roles for embryonic progenitor origin in neurological and neurodevelopmental disorders.

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  • Research Project

Towards therapies for epilepsy: Probing the potential of NMDA receptor allosteric modulation. 01/04/2022 - 31/03/2023

Abstract

Epilepsy is one of the most debilitating brain disorders and to date there is a shortage of drugs to combat it effectively. This is in part the result of the complexity of epileptic seizures, which arise from interactions amongst diverse excitatory and inhibitory neurons expressing numerous ion channels and receptors as well as relevant models. Here we propose to establish two in vitro models of seizure activity, based on mouse hippocampal brain slices and neurons derived from human induced pluripotent stem cells, to investigate the efficacy of novel modulators at one key brain receptor - the glutamatergic NMDA receptor – in controlling seizure activity. In this pilot project we will investigate both positive and negative allosteric NMDA receptor modulators using a combination of electrophysiological techniques including field potential recordings, multi-neuron patch-clamp electrophysiology and multi-electrode array recordings to understand the locus of action of these drugs at the excitatory and inhibitory neurons of the brain and their ability to control seizure activity. This will allow a deeper appreciation of the balance of excitation and inhibition in the generation of seizure activity, reveal the potential of allosteric modulation in controlling seizures and provide the preliminary data for future grant applications to study their effect in vivo.

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  • Research Project

Support maintenance scientific equipment (ENU). 01/01/2022 - 31/12/2023

Abstract

Financial support towards maintenance of scientific equipment in the Experimental Neurobiology Unit (ENU). This includes various electrophysiological setups, behavioural setups, molecular biolology setups and EEG equipment amongst others.

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  • Research Project