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Portrait of two new SOT nucleus members

Basic Science

Portrait of Albano Meli

Albano Meli_2018.jpg

My name is Albano Meli and I am a new member of the Scientists of Tomorrow Nucleus. I studied Cell Physiology at Lille University of Science and Technology (France). I then undertook a PhD at the University of Montpellier under the supervision of Dr. Gérard Molle and Dr. Nathalie Saint at the Centre de Biochimie Structurale (CBS) in Montpellier (France). My PhD was aimed at deciphering the two-partner secretion pathway in Bordetella pertussis bacteria which is responsible for whooping cough, a highly contagious respiratory disease. To that, by using biophysical techniques including single-channel current measurements, I particularly studied the structure-function relationship of FhaC, a pore-forming membrane protein responsible for the secretion of the filamentous hemagglutinin (FHA), a cell surface protein which functions as the main adhesin in Bordetella pertussis. I was able to reveal some distinct domains of FhaC comprising the pore-forming region and binding domains interacting with FHA (Meli et al., JBC 2006). I contributed to the discovery of the first X-ray structure of FhaC, as the member of the Omp85/TpsB family (Clantin et al., Science 2007).

I then moved to New York City and worked as a postdoctoral research scientist at Columbia University Medical Center (USA) for 4 years in Prof. Andrew Marks lab. My research was about the characterization of functional properties of the ryanodine receptor / calcium release channel (RyR) in several pathophysiological conditions. I contributed to explore the consequences of post-translationnal modifications and single-point mutations on the RyR macromolecular complex in the context of inherited cardiac disorders (Meli et al., Circ Res 2011; Meli et al., Int J Cardiol 2014). Although heterologous recombinant and animal models are valuable tools to investigate some key cardiovascular mechanisms, they do not totally recapitulate the patient cardiac phenotype. Therefore, my next research focused on exploiting a new biotechnological tool closer to the patient’s background. I moved to Masaryk University in Brno (Czech Republic) for 2 years as an Assistant Professor in the Department of Cell Biology headed by Prof. Petr Dvorak. I learned about the emerging human induced pluripotent stem cells (hiPSC) and the cardiomyocytes derived from them.

Currently I work at the PhyMedExp laboratory (Inserm U1046, Dir: Prof. Jacques Mercier) in Montpellier (France). This laboratory is specialized in muscle physiology and studies the 3 muscles in healthy and pathophysiological conditions. The team 2, headed by Dr. Alain Lacampagne, investigates the cardiac and skeletal muscle. I actually brought in it my expertise in hiPSC-derived cardiomyocytes to model inherited arrhythmias and congenital cardiomyopathies in the patient-specific molecular and cellular environment to go beyond the underlying mechanisms found in animal and heterologous recombinant models. With 2 PhD students I mentor, we aim at recapitulating dilated cardiomyopathy induced by dystrophin deficiency in Duchenne Muscular Dystrophy (DMD) patients and arrhythmias in polymorphic ventricular tachycardia (CPVT and PVT), with a particular interest in intracellular calcium handling. Our objective is to further validate some of our pathophysiological hypotheses in human and to strengthen our translational interaction with the cardiology department of the Montpellier Hospital.

I have been contributing over the last 4 years to build up a European network between Masaryk University (Czech Rep.) and our lab in Montpellier (France) through several sources of funding (Erasmus, PHC Barrande). Consequently, we have been welcoming foreign students which promotes the European scientific research. Being a Scientist of Tomorrow nucleus member will enable me to pursue the scientific exchange with young investigators in the European Society of Cardiology and promote cardiovascular scientists in training.

 

Portrait of Constanze Schmidt

Constanze Schmidt_2018.jpgMy name is Constanze Schmidt and I am another new member of the Scientists of Tomorrow Nucleus. Between 2003 and 2009 I studied medicine and physics at the Georg-August University of Göttingen in Germany. My dissertation thesis in medicine focused on the development of a new mapping procedure of the visual cortex using functional magnetic resonance imaging to investigate visual fusion at the Georg-August University of Göttingen (Germany). I collected my first scientific experience in the field of ion channels and patch clamp investigation at the Max-Planck Institute for Biophysical chemistry in Göttingen. In 2010 I started my clinical education in internal medicine and cardiology at the Department of Cardiology of Heidelberg University. As physician scientist, I started working in the field of cellular and clinical electrophysiology. During my time as postdoctoral researcher, supported by the Rahel-Goitein-Strauss and Olympia-Morata funding programs (2012 and 2014-2016), I studied the cardiac role of the two-pore domain (K2P) potassium channels, the most recently discovered group of potassium channels, in the human heart. At first, I worked on a molecular and pharmacological characterization of this family of ion channels. Interestingly, molecular and cellular electrophysiological investigations in human atrial cardiomyocytes from patients with atrial fibrillation showed that one member of the K2P-channels, the ion channel TASK-1, has a predominant expression in the atria. It could be observed that its expression was significantly increased in cardiomyocytes of atrial fibrillation patients and that this elevated expression contributed to the shortening of the atrial action potential (Schmidt et al., Circulation 2015; Schmidt et al., European Heart Journal 2017). Therefore, the TASK-1 ion channel represents a promising atrial-selective molecular target for a specific antiarrhythmic therapy in atrial fibrillation. In 2017, I could establish my own laboratory focused on regulation of cardiac ion channels in the pathogenesis of atrial arrhythmopathy and AF-associated remodeling. In particular, my group tries to investigate new pharmacological compounds in animal models of atrial fibrillation to develop new new antiarrhythmic therapies. Mathematical models and large animal models (pigs) of atrial fibrillation are used to include translational and systems biological aspects. Furthermore, in 2015, I developed a mathematical model and a risk score for predicting the risk of patients for developing paroxysmal atrial fibrillation to facilitate an early diagnosis.

In 2016, I received my certification in internal medicine. Since 2017 I am working as an interventional electrophysiologist implanting pacemakers, ICDs and CRT-Ds. My current lab team includes a postdoctoral physician scientist, PhD students in pharmacy and medicine as well as bachelor students in biology and molecular biology.

I am very enthusiastic to be a new member of the Scientist of Tomorrow nucleus, look forward to networking between young scientists, scientist-clinicians and clinicians, and will try to contribute to translational cardiovascular research in the European Society of Cardiology.