What motivated you to dedicate your career to the field of neurogenomics and translational bioinformatics?
My training in medicine and basic neuroscience gave me a broad perspective of the brain in health and disease. My early focus on the stress response system made me very aware of interconnected tissues, cell types and functions needed to form coordinated responses to environmental challenges. Neurogenomics and translational bioinformatics combine all my scientific interests in a unified framework: i) the brain: it involves the integrative analysis of large-scale genetic and brain-specific genomic data and other multi-dimensional brain-related biological data (e.g., neuroimaging); ii) quantitative: compared to the traditional neuroscience disciplines that answer binary (yes/no) questions, this field is involved in the quantitative representation of brain genomic states; iii) translational: the knowledge generated can be transferred (“translated”) to other biological systems (cell models, in silico models, animal models) to generate mechanistic knowledge that can feedback to human research. This translational cycle can accelerate the discovery of reliable biomarkers and effective treatment approaches.
How challenging is to perform translational studies, using integrative systems biology approaches to better understand psychiatric disorders and more specifically, post-traumatic stress disorder (PTSD)?
Translational studies in psychiatry are more challenging compared to other medical disciplines. The original observations are obscured by the incomplete understanding of the brain and its functions. Biopsy or other targeted investigations of the culprit tissue (i.e., the brain) and its cell types (e.g., neurons) is very difficult, and many times is done at the postmortem level, introducing multitude of technical difficulties. It is not a surprise that creating valid translational models of psychiatric disease is a challenge.
In relation to PTSD there are some challenges and unique opportunities. Although a medical condition recognized from ancient times, it was neglected by modern medicine and medical research by being classified as a normative response to a traumatic event. However, it is now recognized that the uniqueness of PTSD is not the experience (unfortunately the traumatic experiences associated with PTSD are frequent in the human life), but the pathologic and chronic types of response occur in subgroups of the population. This made genetic approaches very relevant in trying to understand genomic based biomarkers for PTSD. At the same time, compared to other psychiatric disorders, a well mapped, and preserved across mammals, stress brain circuit and stress physiology provide a unique biological framework for translational studies in PTSD.
What was the biggest obstacle and challenge you ever anticipated in your career path? How did this affect your career development?
I think the more significant challenges are the internal compared to the external. In my case, I was brought up in Athens and I would externally appear as the perfect student, but personally, I thought that my marks did not describe me in an informative way. This did not improve in medical school of Athens that is disproportionally focused on medical education and not so much on medical research. Given that I had this innate tendency to question the knowledge given to me, I felt like an outlier and I volunteered in labs to find my own answers and get the feeling of belonging in the scientific community. Originally, I worked in the lab of Dr. Nicholas Anagnou on gene therapies of thalassemias, but my eye-opening experience was in Dr. Efthimia (Efi) Kitraki’s lab. Efi introduced me to behavioral neuroscience through a project focused on the development of stress axis as a function of early life experiences. This was a key moment for me, which led to an Erasmus scholarship for a research internship at Leiden University (Netherlands) on a related topic. There, I realized that I was not an outlier and that modern medical schools should encourage research and individual paths to knowledge. I find that these early research experiences were very important in my future career steps. In some sense, I am an example of my own research in which early positive or negative experience can program how a developing and aging organism adapt to a future environment.
What would you advise the new students and scientists from Greece who consider pursuing a career/research in the USA?
I think in general perceiving the career in research as a marathon is an important realization. Everybody ideally wants to have an early “Eureka!” moment that would be recognized immediately and guarantee an easy path to success. A young scientist can get inspired by those stories and motivated to start the scientific journey. However, young researchers should also know that most of the times biomedical research is a long process with small incremental steps. Realizing this can empower them and make them more collaborative with a feeling of being part of a communal environment in which all the individual scientific Odysseys are interconnected. This communal path through those challenges is for me the most fulfilling part of science, compared to individual awards.
Where will artificial intelligence and genomic medicine in neuropsychiatric disorders have the largest impact in the coming years?
I think the most impact will be in the redefinition of neuropsychiatric disorders. Right now, neuropsychiatric disorders are heterogeneous, comorbid and genetically overlapping. A biological definition of these disorders involves unsupervised machine learning (i.e., clustering) and the use of genomic and other biological variables together with behavioral/cognitive/clinical variables. Biologically defined subtypes (biotypes) would be accurately diagnosed and more easily targeted therapeutically.
Interviewed by Dr. Krinio Giannikou, General Secretary of HBA-USA, Instructor in Medicine, Harvard Medical School