Department Experimental of Medicine and Pharmaceutical Sciences
University of Perugia
WELCOME at the DIDO website!!!
DIDO is an ERC Advanced Grant Project (ERC-2013-AdG 338954-DIDO) that is
coordinated jointly at the University of Perugia by Prof. Ursula Grohmann
(Principal Investigator; Department of Experimental Medicine) and Prof. Antonio
Macchiarulo (Team Leader; Department of Pharmaceutical Sciences).
The project pools together complementar skillsets and know-how from
multidisciplinary research groups mostly focusing on pharmacology/immunology
and molecular modeling/drug design, with specific regard to indoleamine 2.3 -
dioxygenase 1 (IDO1) biology and IDO1 drug-targeting, thus creating a powerful
platform for significant synergies to achieve the objectives of the project.
Specifically, those are focused on the tryptophan catabolic enzyme IDO1, which
is recognized as an authentic regulator of immunity in several physiopathologic
conditions, including autoimmune diseases, in which it is often defective, and
neoplasia, where it promotes, instead, immune unresponsiveness. Grohmann’s
group recently found that IDO1 does not merely degrade tryptophan and
produce immunoregulatory kynurenines, but it also acts as a signal-transducing
molecule, independently of its enzyme activity. IDO1’s signaling function relies
on the presence of phosphorylable motifs in a region (small IDO1 domain)
distant from the catalytic site (large IDO1 domain). The first objective of DIDO
is to decipher the relationship between conformations and multiple functions of
IDO1. A second aim is to identify small molecules with drug-like properties
capable of modulating distinct IDO1’s molecular conformations in order to either
potentiate (a new therapeutic approach in autoimmune diseases) or inhibit
(more efficient anti-tumor therapeutic strategy) the immunoregulatory signaling
ability of IDO1.
Workshop “Indoleamine2,3-dioxygenase:Interdisciplinary Drug Overview”
Perugia (Italy), June 17, 2015
Ideas take shape to cure many diseases
Dynamics of IDO