Head:	Gianenrico Rovati MD, PhD (Full Professor, Pharmacology)
Team members:	Daniele Bottai PhD (Assistant Professor; Physiology) Alessandro Ieraci PhD (Assistant Professor; Physiology)

 

GENERAL DESCRIPTION

The team has two main research fields focused on one hand on the characterization of the molecular target of lipid mediators, such as leukotriene and thromboxane receptors and their physiological role, and on the other hand the study of neurophysiology with particular focus on the effects of a prolonged muscular inactivity on neurogenesis, neuro-muscular interaction and on the role of gene-environment interaction on the physiopathology of neuropsychiatric and neurodegenerative diseases.

RESEARCH TOPICS

1. Characterization and classification of leukotriene receptors and their physio-pathological role
2. Development and characterization of a new class of dualistic anti-inflammatory drugs
3. Effects of a prolonged muscular inactivity on neurogenesis and neuro-muscular interaction
4. New pharmacological approaches to the spinal muscular atrophy (SMA)
5. Gene-environment interaction on the physiopathology of neuropsychiatric and neurodegenerative diseases
6. Study of the beneficial effects of physical exercise.

 

DESCRIPTION OF THE RESEARCH TOPICS

1. Characterization and classification of leukotriene receptors and their physio-pathological role
This line of research is focused on the study, at a molecular level, of the GPCRs, with particular attention to the leukotriene and thromboxane receptors. Our interest has long been focused on the involvement of these receptors in the respiratory, cardiovascular and neurodegenerative diseases, on their classification, on the discovery of new drugs modulating their activities and on the discovery of new possible molecular targets. Furthermore, the lab is actively engaged in studying the possible cardiovascular protective effects of some drugs already used as anti-asthmatic and, more recently, on their possible role in COVID-19 syndrome (drug repurposing).
The lab is also interested on the functioning of particular P2Y receptors and their cross-talk with the leukotriene system.

Principal collaborations:

• Prof. Richard R. Neubig, Chair of the Department of Pharmacology, Michigan State University, Michigan, USA
• Dr. Magnus Back, Theme Heart and Vessels, Karolinska University Hospital, Division of Valvular and Coronary Disease, Stockholm, Sweden
• Prof. Charles N. Serhan, Director, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women’s Hospital, Harvard Medical School, Boston, USA.
• Dr. Grzegorz Woszczek, UK Centre in Allergic Mechanisms of Asthma, School of Immunology & Microbial Sciences, King's College London, London, UK
• Prof. Marina Camera, Dipartimento di Scienza Farmaceutiche, Università di Milano
• Prof. Luigi Sironi, Dipartimento di Scienza Farmaceutiche, Università di Milano
• Prof. MariaPia Abbracchio, Dipartimento di Scienza Farmaceutiche, Università di Milano
• Dott.sse Bice Chini e Marta Busnelli, Istituto di Neuroscienze-CNR Milano

2. Development and characterization of a new class of dualistic anti-inflammatory drugs
In collaboration with several Italian and European research groups, our lab has been long involved in the development and characterization of a new generation of anti-inflammatory drugs (bivalent molecules) with a better pharmacological and tolerability profile, both from the gastrointestinal and cardiovascular point of view, to be utilized in several chronic inflammatory diseases, including neurodegenerative diseases, and in selected forms of cancer.

Principal collaborations:

• Prof. Dieter Steinhilber Institute of Pharmaceutical Chemistry, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
• Prof. Eugen Proschak Institute of Pharmaceutical Chemistry, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
• Prof. Massimo Bertinaria, Dipartimento di Scienze e tecnologie del Farmaco, UNITO, Torino
• Prof.ssa Paola Patrignani, Dipartimento di Neuroscienze, Imaging e Scienze Cliniche, UNICH, Chieti
• Prof. Angelo Sala, Dipartimento di Scienza Farmaceutiche, Università di Milano

3. Effects of prolonged muscle inactivity on neurogenesis and neuro-muscular interaction
The main aim of this project is to depict the effects of long physical inactivity on mammals' neurogenesis. With this line of research, we plan to continue our study about movement impairment in a healthy animal model in which is induced a reduction of gravity effects as those that represent in people who stay on wheelchair, in bed rest, or astronauts, particularly characterizing a gene/protein that acts as methylthiotransferase which expression is reduced in our mouse hindlimb unloading model and that also seems involved in mitochondria metabolism.

Principal collaborations:

• Prof Monica Canepari, Università degli Studi di Pavia
• Prof Roberto Bottinelli, Università degli Studi di Pavia
• Prof. Paola Rossi, Università degli Studi di Pavia
• Dott.ssa Elisa Roda Istituti Clinici Scientifici MAUGERI SPA SB, IRCCS Pavia

4. New pharmacological approaches to spinal muscular atrophy (SMA)
This study aims to search for new pharmacological approaches that can help SMA patients who have extended lower motor neuron degeneration and consequently cannot be treated with the recently approved drug for SMA. Using a mild SMA model or a cellular model (human SMA iPSCs), in which there is also a low capacity of movement, we plan to perform a comparative analysis with a model of reduction of movement (described in the previous line) with the intent of determining if also in those models there are similar gene expression alteration in particular for CDK5RAP1.

Principal collaborations:

• Prof Monica Canepari, Università degli Studi di Pavia
• Prof Paola Signorelli Università degli Studi di Milano

5. Gene-environment interaction in the physiopathology of neuropsychiatric and neurodegenerative diseases
The aim of this line of research is to investigate how genetic variations (BDNFVal66Met), environmental factors (stress, inflammation, diet, aging) and their interaction can alter the physiology and neuronal plasticity contributing to the onset of neuropsychiatric and neurodegenerative diseases. In particular, we are interest on the possible role of epigenetic mechanisms and oxidative stress. Moreover, we are involved in some studies aimed to investigate the comorbidity between neuropsychiatric and cardiovascular diseases.

Principal collaborations:

• Silvia S. Barbieri; Centro Cardiologico Monzino, Milano.
• Prof.ssa Laura Musazzi; Università degli Studi Milano-Bicocca, Milano.
• Prof.ssa Sarah Beggiato; Univeristà di Ferrara
• Prof.ssa Ilaria Canobbio; Università di Pavia.
• Prof. Alessandro Barbon; Università di Brescia.
• Massimiliano Ruscica; Università degli Studi di Milano.
• Valentina Bollati; Università degli Studi di Milano.

6. Study of the beneficial effects of physical exercise.
The aim of this study is to understand the beneficial effects of physical exercise on brain plasticity and behavior. Our goal is to understand the possible physiological, neuroanatomical, molecular, and epigenetic mechanisms trigger the positive effects of exercise.

Principal collaborations:

• Silvia S. Barbieri; Centro Cardiologico Monzino, Milano.
• Prof.ssa Sarah Beggiato; Univeristà di Ferrara

NETWORK PARTICIPATION
Prof. Rovati is, since 2003, Deputy Chairman of the NC-IUPHAR (International Union of Basic and Clinical Pharmacology) commission for the Nomenclature and classification of leukotriene and lipoxin receptors.
In addition, since 2017 he is also member of the Task Force of the EAACI (European Asthma Allergy and Clinical Immunology) on Eicosanoids in asthma and allergic diseases.