Nicolas Singewald

Biography

Nicolas Singewald is Professor for Pharmacology and heads the Neuropharmacology Unit at the Institute of Pharmacy, Department of Pharmacology and Toxicology, University of Innsbruck, Austria.

He completed his pharmacy studies and obtained his Ph.D. in Drug Development from the Institute of Pharmaceutical Chemistry, University of Innsbruck, Austria. Dr. Singewald started his post-doctoral work at the Department of Pharmacodynamics in Innsbruck focusing on CNS cardiovascular regulation. He then served as an Associate Professor at the Department of Pharmacology and Toxicology investigating effects of interoceptive stimuli on brain neurotransmission and spent 1998 and 1999 as an Erwin Schrödinger Fellow (FWF) at the University of Oxford, UK, Department of Clinical Pharmacology conducting research on anxiety pharmacology. Upon returning to Innsbruck he assumed the role of Head of the Neuropharmacology Unit the Institute of Pharmacy/Pharmacology.

Prof. Singewalds current research interests include the investigation of neurobiological mechanisms and neurocircuitries important in stress, anxiety, and, most recently, anxiety as component in autism. Emphasis is put on understanding individual differences determined by genetic and epigenetic factors, as well as sex and age. The specific neurobiological mechanisms studied include epigenetics, neuroinflammation, neurogenesis. Ultimate aims of the group are to identify relevant biomarkers and develop innovative psychopharmacotherapeutic treatments for mental disorders that can surpass the limited efficacy and side effects associated with existing therapies.

Description of the general focus of the symposium "Exploring New Drugs for Brain Therapy"

This symposium aims to provide an overview of the latest advancements in the dynamic field of neuropharmacology. Focusing on the development and potential applications of novel drugs for brain therapy, the goal of this symposium is to bring together an invited speaker and early-stage career researchers working in this field. Topics covered include novel drug development, emerging therapeutic strategies, and the impact of neuropharmacology on different brain disorders. Early-stage career researchers will present their work on this topic, facilitating discussions on the potential applications of neuropharmacological research in both clinical and experimental settings. Thus, this symposium will provide a platform for interdisciplinary exchange, encouraging collaboration between attendees to advance the understanding and treatment options for brain disorders.

Talk: "Epigenetic modifications in mental disorders and their potential as pharmacological targets" 

There is accumulating evidence that epigenetic mechanisms, such as DNA methylation, histone modifications, and non-coding RNAs, play a contributing role in dysregulated gene expression patterns and brain circuitry dysfunction associated with various neuropsychiatric disorders. One idea is therefore to explore novel pharmacological interventions (“Epipsychopharmacology”) that can modulate epigenetic modifications to restore normal gene expression and circuitry function in these conditions. This involves drugs that target enzymes regulating epigenetic modifications, such as histone deacetylases (HDACs), DNA methyltransferases or utilizing non-coding RNA molecules. In the talk I will discuss the potential of targeting epigenetic mechanisms in anxiety-and trauma-related disorders and will use therapeutic improvement of impaired fear-inhibitory extinction learning as an example. This phenotype is common in PTSD and specific anxiety disorders and is considered an important contributor to treatment resistance in exposure-based therapies. We show that deficits in the formation of fear extinction memories in mice can indeed be normalized by modifying different epigenetic mechanisms. Enhancing histone acetylation via HDAC inhibitors was critical to stabilize the newly built extinction memory in the long-term. Neurons in brain areas known to mediate extinction showed particular increases in histone acetylation and modified activity patterns. Recently, first human exposure therapy trials using repurposed drugs with HDAC inhibitor action have started. Although this research field is still evolving and important challenges including safety, drug specificity and efficacy remain to be further investigated, these findings indicate new ways for the development of improved treatment strategies to overcome treatment-resistance in extinction-driven therapies.