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Systems Biomedicine

Alberto d'Onofrio

[IEO]

Alberto d'Onofrio
alberto.donofriomailifom-ieo-campus.it

 

Research projects

The research of the lab is focused to the application of a wide spectrum of computational and analytical tools of physics and mathematics in both basic science of cancer and clinical oncology.

Indeed, tumors are a family of highly dynamical diseases, so that the nonlinear kinetics of tumor onset and growth shapes both the natural history of neoplasias and their responses to treatments. Moreover, a tumor substantially interacts with its micro-environment, and its nonlinear ‘ecological’ interplay with other systems (e.g. immune system effectors and antibodies, blood vessels etc..) determines its fate.

In particular, our main research topics are the following:

  • Spatial (polarity of dividing cells) and temporal (biochemical oscillations) patterns in cells and cell aggregates. The breaking of symmetry in biochemical networks of reactions is at the base of human life. Cancer deranges those phenomena. For example, cellular differentiation can be read as a loss of spatial symmetry, which in cancer, instead, is partially preserved through, for example, the increase of symmetric division of stem cells. Cell division cycle is an example of breaking of temporal symmetry, leading to periodic phenomenon, whose control in tumors is deranged. An example of onset of ordered structure in time and sometime also in space is given by the glycolytic oscillations.

  • Interplay between stem and progenitor cells in early tumor growth, and its influence on antitumor therapies. The macroscopic growth of a tumor is ruled by changes of the proliferation rate of both stem and progenitor cells. These cells nonlinearly interact, which modulates the expansion of the neoplasm. We study the implications of these interplays in shaping the tumor growth, as well as the response to therapies.

  • Tumor angiogenesis and anti-angiogenic therapies. In vitro tumors have very limited expansion potential, and they reach small diameters. In vivo a landmark of tumor growth is the ability of tumor cells to produce chemicals that attracts and blood vessels, which are ‘embedded’ in order to bring nutrients, i.e. energy. Drugs aimed to stop or kill the tumor blood vessel, named antiangiogenic drugs, have been developed. Preclinical and clinical trials showed that the scheduling of those drugs highly impact on their effectiveness. Biophysical modeling of those phenomena and therapies may be of help in improving the therapies. Moreover, the tumor blood vessel deeply influence the response to classical chemoterapies aimed to target tumor cells.

  • Tumor-Immune System (IS) interplay. Immune surveillance and tumor evasion from it, tumor-IS equilibrium, immuno-therapies: those phenomena are all complex, nonlinear and to some extent adaptive. However, we showed how their main features can be captured by some simple mathematical models.

  • Role of intrinsic and extrinsic biological ‘noise’ in shaping intra- and inter-cellular phenomena, including chemoresistance. A biological system is affected by large internal statistical fluctuations, and by external fluctuations that are ‘transmitted to it by the other systems with which it interacts’. Our models suggests that those fluctuation can sometime be ‘positive’ for the tumor (e.g. the external fluctuations of adaptive immunity could help them to evade from immune control; the fluctuation in drug clearance and pharmacodynamics might induce non-genetic patterns of resistance to chemotherapies), and in some case ‘negative’ (e.g. the internal fluctuation of the number of tumor cells could significantly help the tumor suppression by the immune system).

  • In-host spreading and therapy of tumor-related infectious diseases (ID). Infectious diseases are per se a danger for public health, but they are sometime related to the onset of tumors. We study mathematical models of the in-host spreading to the related pathogens, aw well as therpies (e.g. antiviral therapies and their scheduling)

  • In-population spreading and therapy of tumor-related infectious diseases (ID). Vaccines are very important factor for cancer prevention. We investigate how rumors and the media can shape the vaccination behavior (as well the ID-related behaviors tout-court) of individuals.

  • Biomechanical and dielectric properties of physiologic and tumor tissues. We recently started applying recent methodologies of non-equilibrium thermodynamics to the study of some physical properties of physiological and tumor tissues, through a series of experimental and theoretical analyses.

  • Philosophy and Sociology of Science. The activity of biomedical research must not be uniquely confined in our wet or in-silico labs. We have to reason on the ethical aspect and implications of our research, as well as on the philosophical bases of our scientific activity.

  • Epidemiology of Cancer in Europe: spatial and temporal issues.

  • …who knows?
    Theoretical research is strongly driven by curiosity, thus new topic not included in this list could soon be added with relative ease!

 

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update: September 2010
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