Joseph Italiano

Department of Medicine
Brigham and Women's Hospital
Karp Research Building, 6th Floor, Room 214
1 Blackfan Circle
Boston, MA 02115
Tel: (617) 355-9007
Fax: (617) 355-9016
Email: jitaliano@rics.bwh.harvard.edu

Our laboratory studies how blood platelets, which function as the bandaids of the bloodstream, are produced from megakaryocyte precursor cells. Megakaryocytes are terminally differentiated cells that in their final hours convert into long, branched proplatelets. We have demonstrated that platelet formation follows a defined set of morphogenetic shape changes driven by forces derived from both microtubules and actin filaments. The overall goal of our research is to elucidate the cytoskeletal mechanics and signaling pathways that culminate in the formation of platelets.

Specifically, the lab uses a mouse megakaryocyte culture system to study platelet production in vitro. Our primary methods include fluorescence microscopy, molecular biology, biochemistry, electron microscopy, and knockout mice. Where possible, we attempt to study the dynamics of proteins in living megakaryocytes or reconstitute cellular process with cell extracts. Current focuses include understanding how microtubule-based forces power the elongation of proplatelets, probing how organelles are transported into platelets, establishing how the spectrin-based membrane skeleton contributes to platelet formation, and determining how actin dynamics powers the formation of platelets.

References:

Patel, S., Richardson, J, Schulze, H., Kahle, E., Galjart, N., Drabek, K., Shivdasani, R.A., Hartwig, J and J.E Italiano. 2005. Differential roles of microtubule assembly and sliding in proplatelet formation by megakaryocytes. Blood. 106:4076-4085.
Richardson, J., Shivdasani, R.A., Boers, C., Hartwig, J., Hartwig, J and J.E. Italiano. 2005. Mechanisms of organelle transport and capture along proplatelets during platelet production. Blood. Vol. 100. Blood. 106:4066-4075.
Patel, S.R., Hartwig, J.H., and J.E. Italiano. 2005. The biogenesis of platelets from megakaryocyte proplatelets. Journal of Clinical Investigation. 115:3348-3354.

BBS webpage updated 12/02/2009