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Leukocyte Biology

P.I.: Massimo Locati, MD
Università degli Studi di Milano

Research Activities Massimo Locati Publications
The Leukocyte Biology Lab is mainly focused on cellular and molecular mechanisms involved in the control of leukocyte recruitment and activation during an inflammatory response.
 
A first research line is focused on chemokines, a large family of cytokines with chemotactic activity controlling leukocyte recruitment during inflammatory responses. In particular, in the recent past the lab has significantly contributed to the identification of chemokine scavenger receptors as an emerging family of regulators with a relevant role in several pathological conditions. The lab has identified D6 as the first chemokine decoy receptor with scavenger activity, has investigated the structural determinants supporting this biological function (scavenging, cycling, and signalling properties), and has demonstrated its non-redundant role in vivo in different models of inflammation (CFA injection, LPS-driven fetal loss, SDS-driven colitis), infection (TB) and tumor (inflammation-driven colon cancer). The lab has also collaborated in these last years with pharma companies to develop new inhibitors of this molecular system. In particular, it has provided significant contribution to the understanding of the mechanism of action of allosteric non-competitive chemokine receptor inhibitors, and more recently it has been involved in the functional characterization of molecules inhibiting chemokines production, as a promising alternative approach to receptor inhibitors.
 
A second research line focuses on macrophages, which play a central role during an inflammatory response linking innate and adaptive immunity and coordinating tissue remodelling and healing. These pleiotropic functions are the result of tissue-derived signals that lead to different types of cell activation. The lab has first described the complete transcriptional profile of human macrophages undergoing classical (M1) or alternative (M2) polarized activation, and has identified new signatures and molecular markers, some of which are presently under investigation in the lab.
 
A third and more recent research line investigates the role of microRNA in the activation of phagocytes in response to inflammatory stimuli. The lab has identified new microRNA associated to this process, and is presently investigating the complex network connecting microRNA and transcriptional factors with a recognized role in inflammatory conditions.

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