(Head of the Laboratory)
Christian Andrea Di Buduo
Models of megakaryocyte functions
Platelets derived from megakaryocytes (Mks) in the bone marrow play a central role in many physiological functions. However, there are many platelet-related diseases for which there are no current treatments other than palliative therapies, resulting in serious complications and side effects. Unraveling mechanisms of functional platelet formation from megakaryocytes would provide new options for therapeutic interventions. In our laboratory we pursue the understanding of these mechanisms by connecting medicine with biology, biotechnology and bioengineering research approaches. This synergistic network covers a number of relevant disciplines and expertise, including biochemistry, cell biology, molecular biology, biophysics, science of materials and clinic. The current work of the laboratory focuses on four lines of investigation:
(i) Extracellular matrix component-Mk interactions in the bone marrow environment (Malara et al., Blood 2011, 118(16): 4449-53; Malara et al., Stem Cells 2014, 32(4): 926-37)
(ii) 3D models, based on silk biomaterials, to study bone marrow platelet formation (Di Buduo et al., Blood 2015, 125(14): 2254-64)
(iii) Autocrine mechanisms and calcium flux in Mk functions (Di Buduo et al., Haematologica 2014, 99(4): 769-78)
(iv) Altered mechanisms of Mk functions in pathologic states (Bluteau et al., J Clin Invest. 2014, 124(2): 580-91)
Selected PapersProgrammable 3D silk bone marrow niche for platelet generation ex vivo and modeling of megakaryopoiesis pathologies. Di Buduo CA, Wray LS, Tozzi L, Malara A, Chen Y, Ghezzi CE, Smoot D, Sfara C, Antonelli A, Spedden E, Bruni G, Staii C, De Marco L, Magnani M, Kaplan DL, Balduini A. Blood 125(14): 2254-64 (2015).
Discoidin Domain Receptor 1 is a novel modulator of megakaryocyte-collagen interactions. Abbonante V, Gruppi C, Rubel D, Gross O, Moratti R, Balduini A. J Biol Chem. 288(23): 16738-46 (2013).
Megakaryocyte-matrix interaction within bone marrow: new roles for fibronectin and factor XIII-A. Malara A, Gruppi C, Rebuzzini P, Visai L, Perotti C, Moratti R, Balduini C, Tira ME, Balduini A. Blood 117(8): 2476-83 (2011).