Scientific Activity
Formerly the research activity was devoted to the study of molecular interaction between drugs and oligonucleotides, and to the synthesis of L-nucleotides in liquid phase. These studies contributed to elucidate the mechanism by which distamycins binds to the DNA minor groove and to discover that L-thymidine is selectively phosphorylated by thymidine kinase of the herpes simplex virus type 1 and not by the human thymidine kinase. This finding led to patent the L-thymidine and its derivative as antiviral drugs.
Then, the research activity moved to the in vivo magnetic resonance spectroscopy (MRS) to study non invasively the metabolic pathways in living tissues contributing to the development of in vivo magnetic resonance spectroscopy both in basic research and in diagnostic applications. In addition a relevant body of the research activity by MRS has been directed to the study of pathogenetic mechanisms and to the therapy effects of several neuronal and neuromuscular diseases
The phosphorus MRS (31P-MRS) was employed to explore in vivo the energetic metabolism functionality of human brain and skeletal muscle both in physiologic and pathologic conditions.
The 31P-MRS studies on the kinetics of the of the Pi signal decay after muscular contraction showed to be related to the mechanisms of Pi transport into mitochondria. This finding put the basis to create a new experimental approach to study directly in vivo the kinetics Pi transport. This allowed to build a model of the mechanism of Pi transport into mitochondria, which in turn leaded to find an impairment of the kinetics of Pi transport in the skeletal muscle of Duchenne/Becker carriers. On the basis of this finding a new non invasive diagnostic test was proposed to disclose the carrier status in relatives of Duchenne/Becker patients, particularly useful when the proband is not available to perform molecular genetic analysis.
The studies of the kinetics of phosphocreatine re-synthesis after muscular exercise contributed to create a non invasive method to assess the functionality of mitochondrial respiration proposing the 31P-MRS as new diagnostic tool for the muscular mitochondrial pathologies.
An other important achievement was reached in the study of the role of oxygen in the regulation of oxidative phosphorylation in skeletal muscle combining near infrared spectroscopy (NIRS) and 31P-MRS, showing that in normoxic conditions the oxygen availability is not limiting the oxidative phosphorylation even at maximal rate of energy requirements
The further development of the research on the energetic metabolism required the design of a qualitative and quantitative chemical model describing the interactions between the phosphorylated molecules mainly involved in the energetic pathway and the ions present in the cellular environment. This model has been used to build original methods to quantify in vivo by 31P-MRS the cytosolic pH and the free cytosolic [Mg2+] in human brain and skeletal muscle.
Subsequently, the research activity has been devoted: i) to the re-definition of the equilibrium constants of phosphorylated metabolites involved in the energetic metabolism taking into account the influence of magnesium measured in vivo by 31P-MR; ii) to the design and development of quantitative mathematical approach for the in vivo assessment of tissue thermodynamics; iii) to the development of an absolute quantification method of the metabolites detectable by proton magnetic resonance spectroscopy (1H-MRS) in order to enlarge the diagnostic value of MRS; iv)to the design and development of new radiofrequency surface coils for MRS equipments with improved sensitivity and spatial selectivity which resulted in two co-authored patents.
An international scientific acknowledgement is the appointment as Task Group Chair of the PROJECT TITLED: “CHEMICAL AND BIOCHEMICAL THERMODYNAMICS REUNIFICATION” (#2017-021-2-100) by IUPAC - Physical and Biophysical Chemistry Division. This achievement is related to the conceptualization of a novel procedure developed to simplify the treatment of the thermodynamics of complex systems. The procedure proposed can be applied to any biochemical reaction, making possible to re-unify the two worlds of chemical and biochemical thermodynamics, which so far have been treated separately, and represents a new paradigm in the biochemical thermodynamics.
At present, part of the activity is directed to the study of magnesium homeostasis in living cells by confocal microscopy and fluorimetric techniques using a new class of fluorescent sensors recently developed whose improved synthesis has been patented.
The most recent research activity is devoted to the study the early stages of bone mineralization mechanisms in differentiated bone marrow stem cells by Synchrotron based X-ray techniques exploiting the partnership with the Research Centers of APS Argonne (Chicago), Elettra (Trieste), ESRF (Grenoble), ALBA (Barcelona). In this regard, a crucial part of this research activity is aimed at the development of a multi-modal approach integrating post-processing analysis software of x-ray nanotomography and X-ray Absorption Near-Edge spectro-microscopy.
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