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Joseph E. Italiano, Jr., Ph.D.
Associate Biologist, Brigham and Women's Hospital
Associate Professor of Medicine, Harvard Medical School

Brigham and Women's Hospital
Department of Medicine
Hematology
75 Francis Street
Boston, MA 02115


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Research Narrative:

Joseph Italiano received a Ph.D. from Florida State University and completed a National Institutes of Health postdoctoral fellowship at Brigham and Women's Hospital. He is the recipient of a number of NIH grants. His awards and honors include the American Society of Hematology Scholar Award and American Heart Foundation Scientist Development Grant.

The Italiano Lab has had a long-standing interest in identifying and characterizing the biochemical and molecular mechanisms underlying the production of platelets. Blood platelets function as the bandaids of the bloodstream. They are produced from giant precursor cells called megakaryocytes. Megakaryocytes generate platelets by remodeling their cytoplasm into long cytoplasmic extensions called proplatelets, which serve as assembly lines for platelet production. Dr. Italiano and his group have identified cytoskeletal pathways that are required for platelet biogenesis. They have demonstrated that platelet formation follows a defined set of morphogenetic shape changes driven by forces derived from both microtubules and actin filaments. Elucidation of the cell biological and signaling pathways that culminate in the formation of platelets should yield strategies for accelerating platelet counts in patients with thrombocytopenia.

In addition, the Italiano Lab has investigated the role of blood platelets in regulating new blood vessel development, or angiogenesis. They have established that pro- and anti-angiogenic regulatory proteins are stored in separate and distinct alpha-granules in platelets, and that these distinct populations of alpha-granules are susceptible to differential release. Significant efforts are now underway in the lab to identify the mechanisms by which angiogenic regulatory proteins are packaged into distinct granules and to establish the pathways that regulate their selective release. A better understanding of the mechanisms by which platelets regulate angiogenesis should yield strategies for pro- and anti-angiogenic therapy.


Education:
Florida State Univ., 1997, Ph.D.

Publications (Pulled from Harvard Catalyst Profiles):

1. Bhatlekar S, Basak I, Edelstein LC, Campbell RA, Lindsey CR, Italiano JE, Weyrich AS, Rowley JW, Rondina MT, Sola-Visner M, Bray PF. Anti-apoptotic BCL2L2 increases megakaryocyte proplatelet formation in cultures of human cord blood. Haematologica. 2019 Feb 07.

2. Johnson KE, Ceglowski JR, Roweth HG, Forward JA, Tippy MD, El-Husayni S, Kulenthirarajan R, Malloy MW, Machlus KR, Chen WY, Italiano JE, Battinelli EM. Aspirin inhibits platelets from reprogramming breast tumor cells and promoting metastasis. Blood Adv. 2019 Jan 22; 3(2):198-211.

3. Noetzli LJ, Italiano JE. Unlocking the Molecular Secrete(s) of a-Granule Biogenesis. Arterioscler Thromb Vasc Biol. 2018 Nov; 38(11):2539-2541.

4. Cloutier N, Allaeys I, Marcoux G, Machlus KR, Mailhot B, Zufferey A, Levesque T, Becker Y, Tessandier N, Melki I, Zhi H, Poirier G, Rondina MT, Italiano JE, Flamand L, McKenzie SE, Cote F, Nieswandt B, Khan WI, Flick MJ, Newman PJ, Lacroix S, Fortin PR, Boilard E. Platelets release pathogenic serotonin and return to circulation after immune complex-mediated sequestration. Proc Natl Acad Sci U S A. 2018 02 13; 115(7):E1550-E1559.

5. Lorenz V, Ramsey H, Liu ZJ, Italiano J, Hoffmeister K, Bihorel S, Mager D, Hu Z, Slayton WB, Kile BT, Sola-Visner M, Ferrer-Marin F. Developmental Stage-Specific Manifestations of Absent TPO/c-MPL Signalling in Newborn Mice. Thromb Haemost. 2017 12; 117(12):2322-2333.

6. Zufferey A, Speck ER, Machlus KR, Aslam R, Guo L, McVey MJ, Kim M, Kapur R, Boilard E, Italiano JE, Semple JW. Mature murine megakaryocytes present antigen-MHC class I molecules to T cells and transfer them to platelets. Blood Adv. 2017 Sep 12; 1(20):1773-1785.

7. Paul DS, Casari C, Wu C, Piatt R, Pasala S, Campbell RA, Poe KO, Ghalloussi D, Lee RH, Rotty JD, Cooley BC, Machlus KR, Italiano JE, Weyrich AS, Bear JE, Bergmeier W. Deletion of the Arp2/3 complex in megakaryocytes leads to microthrombocytopenia in mice. Blood Adv. 2017 Aug 08; 1(18):1398-1408.

8. Machlus KR, Wu SK, Vijey P, Soussou TS, Liu ZJ, Shacham E, Unger TJ, Kashyap T, Klebanov B, Sola-Visner M, Crochiere M, Italiano JE, Landesman Y. Selinexor-induced thrombocytopenia results from inhibition of thrombopoietin signaling in early megakaryopoiesis. Blood. 2017 08 31; 130(9):1132-1143.

9. Cunin P, Penke LR, Thon JN, Monach PA, Jones T, Chang MH, Chen MM, Melki I, Lacroix S, Iwakura Y, Ware J, Gurish MF, Italiano JE, Boilard E, Nigrovic PA. Megakaryocytes compensate for Kit insufficiency in murine arthritis. J Clin Invest. 2017 May 01; 127(5):1714-1724.

10. Johnson KE, Forward JA, Tippy MD, Ceglowski JR, El-Husayni S, Kulenthirarajan R, Machlus KR, Mayer EL, Italiano JE, Battinelli EM. Tamoxifen Directly Inhibits Platelet Angiogenic Potential and Platelet-Mediated Metastasis. Arterioscler Thromb Vasc Biol. 2017 04; 37(4):664-674.