Philippe A. Melas

As an independent researcher at the Center for Psychiatry Research (CPF), I'm fascinated by the complexity of substance use disorders and the underlying molecular and genetic mechanisms that contribute to addiction. My academic journey started with a Bachelor's degree in Molecular Biology and Genetics from Democritus University in Greece, followed by a master's degree in Genetic Counseling at Uppsala University. During my PhD studies at Karolinska Institutet, I focused on using molecular and epigenetic methodologies to investigate psychiatric disorders such as depression and schizophrenia. After completing my PhD, I joined Dr. Eric Kandel's lab at Columbia University as a postdoctoral fellow, where I gained valuable insights into brain reward systems and their dysregulation in substance use and addiction. Since returning to Karolinska Institutet as an independent researcher in 2020, my research has expanded to include the study of epitranscriptomics and proteomics in substance use disorders. Through my research, I hope to shed light on the underlying molecular mechanisms of addiction and contribute to the development of new, personalized treatments.

Overview
My research is dedicated to understanding the molecular, genetic, epigenetic and epitranscriptomic components driving substance use disorders, commonly known as addiction. My recent work has focused primarily on alcohol use disorder (AUD), which impacts approximately 5% of the global population and is a significant burden on mental health systems worldwide. In Sweden alone, over 300, 000 people are estimated to struggle with AUD. More specifically, my latest research aims to investigate the roles of the RNA-demethylating enzyme FTO and m6A RNA methylation in the development of AUD. Recent genome-wide association studies have identified significant associations between the FTO gene and various alcohol use phenotypes, including AUD. However, there is a lack of studies examining the causal and functional roles of FTO and m6A RNA methylation in AUD development. In parallel, I lead a second, independent line of research in subcellular brain proteomics, where we map proteomic disease signatures in the human insula (cytosol, nucleus, synapse) and link them to drug repurposing; a strategy that has already identified several promising candidates for preclinical validation. By conducting a multidisciplinary investigation using animal models, primary neurons, and human postmortem brain tissue, we hope to advance our understanding of the underlying molecular mechanisms contributing to alcohol use disorders. Our approach includes a combination of behavioral neuroscience, molecular biology, and bioinformatics methods. We have assembled a team of experts in each of these fields, and established international collaborations with other PIs to ensure that we have access to the latest technology and techniques. We aim to uncover new insights that could lead to the development of novel, targeted therapeutics for AUD with the potential to significantly improve clinical outcomes.

Project funding
For my research as a PI, I am grateful to have received project support from a range of funding sources, including the Swedish Research Council, the Swedish Brain Foundation, the Alcohol Research Council of the Swedish Alcohol Retailing Monopoly, the Åke Wibergs Foundation, the Petrus and Augusta Hedlunds Foundation, the Magnus Bergvall Foundation, the Royal Physiographic Society in Lund, the Sigurd and Elsa Goljes Minne Foundation, the Lars Hiertas Minne Foundation, the Loo and Hans Ostermans Foundation, Karolinska Institutet's Research Grants, and the Längmanska Foundation. These grants have enabled me to pursue my research and have contributed to the advancement of the field of addiction research.

Fellowships and Awards
I have also been honored to receive several awards and postdoctoral fellowships during my early academic career. These include the international postdoc grant from the Swedish Research Council, postdoctoral grants from the Sweden-America Foundation, the Royal Physiographic Society in Lund, and the Fernströms Foundation, as well as doctoral fellowships from Karolinska Institutet (KID) and the Bodossaki Foundation in Greece. I have also received research and/or conference travel awards from Karolinska Institutet, Roche Continents, and the National Institute on Drug Abuse (NIDA) in the USA. These awards have provided me with opportunities to pursue my academic interests and have inspired me to continue to contribute to the field of molecular psychiatry.