Welcome to the Italiano Lab. Our research uses cell and molecular biology methods to address problems in megakaryocyte and platelet biology. The lab’s research focuses primarily on how blood platelets, which function as the band-aids of the bloodstream, are produced from megakaryocyte precursor cells. Specifically, the lab uses mouse megakaryocyte and human culture systems to study platelet production in vitro. Our primary methods include fluorescence microscopy, live cell imaging, molecular biology, biochemistry, electron microscopy, bioengineering, and knockout mice. Where possible, we attempt to study the dynamics of proteins in living megakaryocytes or reconstitute cellular process with cell extracts. Our lab has demonstrated that platelet formation follows a defined set of morphogenetic shape changes driven by forces derived from both microtubules and actin filaments. Current focuses include understanding the molecular signals that trigger platelet production, using biologically inspired engineering to establish how the bone marrow microenvironment influences platelet production, understanding how the cytoskeleton powers platelet production. We also have a major interest in understanding the non-hemostatic roles of platelets in health and disease. This includes establishing how platelets regulate new blood vessel growth, immunity, cancer, wound healing, and potentially aging..
Research Background
Joseph Italiano is an Associate Professor who holds academic appointments at Boston Children’s Hospital and Harvard Medical School. He was awarded his Ph.D. in Cell Biology from Florida State University, under the supervision of Thomas Roberts. His thesis focused on how filament assembly and bundling contribute towards cell crawling in amoeboid sperm of Ascaris. Since then, Dr. Italiano transitioned into hematology-based research with John Hartwig at Brigham and Women’s Hospital, where he first began studying the cytoskeletal mechanisms of blood platelet formation, which remains a focus of his work as a Principal Investigator at the Boston Children's Hospital
Publications
Serglycin controls megakaryocyte retention of platelet factor 4 and influences megakaryocyte fate in bone marrow. Blood Adv. 2025 Jan 14; 9(1):15-28. View Abstract
Looking Under the Hood at the Cytoskeletal Engine of Platelet Production. Arterioscler Thromb Vasc Biol. 2025 Feb; 45(2):186-197. View Abstract
Inhibition of RhoA-mediated secretory autophagy in megakaryocytes mitigates myelofibrosis in mice. bioRxiv. 2024 Dec 05. View Abstract
Shear Stress Promotes Remodeling of Platelet Glycosylation via Upregulation of Platelet Glycosidase Activity: One More Thing. Thromb Haemost. 2024 Sep 12. View Abstract
Targeting cargo to an unconventional secretory system within megakaryocytes allows the release of transgenic proteins from platelets. J Thromb Haemost. 2024 Nov; 22(11):3235-3248. View Abstract
What It Takes To Be a Platelet: Evolving Concepts in Platelet Production. Circ Res. 2024 Aug 02; 135(4):540-549. View Abstract
Evidence for a cytoplasmic proplatelet promoting factor that triggers platelet production. Haematologica. 2024 07 01; 109(7):2341-2345. View Abstract
The bone marrow is the primary site of thrombopoiesis. Blood. 2024 01 18; 143(3):272-278. View Abstract
Thrombopoietin levels in sepsis and septic shock - a systematic review and meta-analysis. Clin Chem Lab Med. 2024 Apr 25; 62(5):999-1010. View Abstract
Efficient megakaryopoiesis and platelet production require phospholipid remodeling and PUFA uptake through CD36. Nat Cardiovasc Res. 2023 Aug; 2(8):746-763. View Abstract
Sodium bicarbonate as a local adjunctive agent for limiting platelet activation, aggregation, and adhesion within cardiovascular therapeutic devices. J Thromb Thrombolysis. 2023 Oct; 56(3):398-410. View Abstract
A Critical Role for ERO1a in Arterial Thrombosis and Ischemic Stroke. Circ Res. 2023 05 26; 132(11):e206-e222. View Abstract
Spatial transcriptomics of murine bone marrow megakaryocytes at single-cell resolution. Res Pract Thromb Haemost. 2023 May; 7(4):100158. View Abstract
Shear-Mediated Platelet Microparticles Demonstrate Phenotypic Heterogeneity as to Morphology, Receptor Distribution, and Hemostatic Function. Int J Mol Sci. 2023 Apr 17; 24(8). View Abstract
Proceedings of the immune thrombocytopenia summit: new concepts in mechanisms, diagnosis, and management. Res Pract Thromb Haemost. 2023 Feb; 7(2):100097. View Abstract
Efficient megakaryopoiesis and platelet production require phospholipid remodeling and PUFA uptake through CD36. bioRxiv. 2023 Feb 12. View Abstract
Shear-Mediated Platelet Microparticles Demonstrate Phenotypic Heterogeneity as to Morphology, Receptor Distribution, and Hemostatic Function. bioRxiv. 2023 Feb 08. View Abstract
Platelets upregulate tumor cell programmed death ligand 1 in an epidermal growth factor receptor-dependent manner in vitro. Blood Adv. 2022 10 25; 6(20):5668-5675. View Abstract
Pro-inflammatory megakaryocyte gene expression in murine models of breast cancer. Sci Adv. 2022 10 14; 8(41):eabo5224. View Abstract
DNA Origami-Platelet Adducts: Nanoconstruct Binding without Platelet Activation. Bioconjug Chem. 2022 07 20; 33(7):1295-1310. View Abstract
Don't you forget about me(gakaryocytes). Blood. 2022 06 02; 139(22):3245-3254. View Abstract
The triple crown of platelet generation. Blood. 2022 04 07; 139(14):2100-2101. View Abstract
Sequence-specific 2'-O-methoxyethyl antisense oligonucleotides activate human platelets through glycoprotein VI, triggering formation of platelet-leukocyte aggregates. Haematologica. 2022 02 01; 107(2):519-531. View Abstract
The secreted tyrosine kinase VLK is essential for normal platelet activation and thrombus formation. Blood. 2022 01 06; 139(1):104-117. View Abstract
Microvesicles, but not platelets, bud off from mouse bone marrow megakaryocytes. Blood. 2021 11 18; 138(20):1998-2001. View Abstract
Evolving perspectives on mechanical circulatory support biocompatibility and interfaces. Ann Cardiothorac Surg. 2021 May; 10(3):396-398. View Abstract
Shear-mediated platelet activation in the free flow II: Evolving mechanobiological mechanisms reveal an identifiable signature of activation and a bi-directional platelet dyscrasia with thrombotic and bleeding features. J Biomech. 2021 06 23; 123:110415. View Abstract
Transfer to the clinic: refining forward programming of hPSCs to megakaryocytes for platelet production in bioreactors. Blood Adv. 2021 04 13; 5(7):1977-1990. View Abstract
Platelet Dysfunction During Mechanical Circulatory Support: Elevated Shear Stress Promotes Downregulation of aIIbß3 and GPIb via Microparticle Shedding Decreasing Platelet Aggregability. Arterioscler Thromb Vasc Biol. 2021 04; 41(4):1319-1336. View Abstract
VWF maturation and release are controlled by 2 regulators of Weibel-Palade body biogenesis: exocyst and BLOC-2. Blood. 2020 12 10; 136(24):2824-2837. View Abstract
High-content, label-free analysis of proplatelet production from megakaryocytes. J Thromb Haemost. 2020 10; 18(10):2701-2711. View Abstract
Platelet Dysfunction and Thrombosis in JAK2V617F-Mutated Primary Myelofibrotic Mice. Arterioscler Thromb Vasc Biol. 2020 10; 40(10):e262-e272. View Abstract
Platelet-derived extracellular vesicles infiltrate and modify the bone marrow during inflammation. Blood Adv. 2020 07 14; 4(13):3011-3023. View Abstract
Sniffing out the aroma(tase) of drug-induced thrombocytopenia. Blood. 2020 06 11; 135(24):2116-2117. View Abstract
Platelet Activation via Shear Stress Exposure Induces a Differing Pattern of Biomarkers of Activation versus Biochemical Agonists. Thromb Haemost. 2020 May; 120(5):776-792. View Abstract
Yin and Yang of MCS-Related Coagulopathy: Shear Stress Promotes Platelet Prothrombosis and Microparticle Generation While Inducing Integrin Downregulation and Decreased Aggregability. J Heart Lung Transplant. 2020 Apr; 39(4S):S177. View Abstract
Megakaryocyte Reprogramming in Breast Cancer. Blood. 2019 Nov 13; 134(Supplement_1):12. View Abstract
VWF Exocytosis and Biogenesis of Weibel Palade Bodies in Endothelial Cells Are Differentially Controlled By Interactions between Bloc-2 and the Exocyst Complex. Blood. 2019 Nov 13; 134(Supplement_1):8. View Abstract
Megakaryocytes package contents into separate a-granules that are differentially distributed in platelets. Blood Adv. 2019 10 22; 3(20):3092-3098. View Abstract
Megakaryocyte emperipolesis mediates membrane transfer from intracytoplasmic neutrophils to platelets. Elife. 2019 05 01; 8. View Abstract
Anti-apoptotic BCL2L2 increases megakaryocyte proplatelet formation in cultures of human cord blood. Haematologica. 2019 10; 104(10):2075-2083. View Abstract
Aspirin inhibits platelets from reprogramming breast tumor cells and promoting metastasis. Blood Adv. 2019 01 22; 3(2):198-211. View Abstract
Unlocking the Molecular Secrete(s) of a-Granule Biogenesis. Arterioscler Thromb Vasc Biol. 2018 11; 38(11):2539-2541. View Abstract
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. View Abstract
Developmental Stage-Specific Manifestations of Absent TPO/c-MPL Signalling in Newborn Mice. Thromb Haemost. 2017 12; 117(12):2322-2333. View Abstract
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. View Abstract
Deletion of the Arp2/3 complex in megakaryocytes leads to microthrombocytopenia in mice. Blood Adv. 2017 Aug 08; 1(18):1398-1408. View Abstract
Selinexor-induced thrombocytopenia results from inhibition of thrombopoietin signaling in early megakaryopoiesis. Blood. 2017 08 31; 130(9):1132-1143. View Abstract
Megakaryocytes compensate for Kit insufficiency in murine arthritis. J Clin Invest. 2017 May 01; 127(5):1714-1724. View Abstract
DREAM plays an important role in platelet activation and thrombogenesis. Blood. 2017 01 12; 129(2):209-225. View Abstract
Human thrombopoiesis depends on Protein kinase Cd/protein kinase Ce functional couple. Haematologica. 2016 07; 101(7):812-20. View Abstract
Lysyl oxidase is associated with increased thrombosis and platelet reactivity. Blood. 2016 Mar 17; 127(11):1493-501. View Abstract
Synthesis and dephosphorylation of MARCKS in the late stages of megakaryocyte maturation drive proplatelet formation. Blood. 2016 Mar 17; 127(11):1468-80. View Abstract
CCL5 derived from platelets increases megakaryocyte proplatelet formation. Blood. 2016 Feb 18; 127(7):921-6. View Abstract
Cytoskeletal perturbation leads to platelet dysfunction and thrombocytopenia in variant forms of Glanzmann thrombasthenia. Haematologica. 2016 Jan; 101(1):46-56. View Abstract
Abnormal megakaryopoiesis and platelet function in cyclooxygenase-2-deficient mice. Thromb Haemost. 2015 Nov 25; 114(6):1218-29. View Abstract
Road blocks in making platelets for transfusion. J Thromb Haemost. 2015 Jun; 13 Suppl 1:S55-62. View Abstract
Expansion of the neonatal platelet mass is achieved via an extension of platelet lifespan. Blood. 2014 May 29; 123(22):3381-9. View Abstract
Interpreting the developmental dance of the megakaryocyte: a review of the cellular and molecular processes mediating platelet formation. Br J Haematol. 2014 Apr; 165(2):227-36. View Abstract
Macrocytic anemia and mitochondriopathy resulting from a defect in sideroflexin 4. Am J Hum Genet. 2013 Nov 07; 93(5):906-14. View Abstract
Anticoagulation inhibits tumor cell-mediated release of platelet angiogenic proteins and diminishes platelet angiogenic response. Blood. 2014 Jan 02; 123(1):101-12. View Abstract
Unraveling mechanisms that control platelet production. Semin Thromb Hemost. 2013 Feb; 39(1):15-24. View Abstract
Netrin-1 promotes glioblastoma cell invasiveness and angiogenesis by multiple pathways including activation of RhoA, cathepsin B, and cAMP-response element-binding protein. J Biol Chem. 2013 Jan 25; 288(4):2210-22. View Abstract
Canonical Wnt signaling in megakaryocytes regulates proplatelet formation. Blood. 2013 Jan 03; 121(1):188-96. View Abstract
The microtubule plus-end tracking protein CLASP2 is required for hematopoiesis and hematopoietic stem cell maintenance. Cell Rep. 2012 Oct 25; 2(4):781-8. View Abstract
A GWAS sequence variant for platelet volume marks an alternative DNM3 promoter in megakaryocytes near a MEIS1 binding site. Blood. 2012 Dec 06; 120(24):4859-68. View Abstract
Differential roles of cAMP and cGMP in megakaryocyte maturation and platelet biogenesis. Exp Hematol. 2013 Jan; 41(1):91-101.e4. View Abstract
Altered microtubule equilibrium and impaired thrombus stability in mice lacking RanBP10. Blood. 2012 Oct 25; 120(17):3594-602. View Abstract
T granules in human platelets function in TLR9 organization and signaling. J Cell Biol. 2012 Aug 20; 198(4):561-74. View Abstract
MKL1 and MKL2 play redundant and crucial roles in megakaryocyte maturation and platelet formation. Blood. 2012 Sep 13; 120(11):2317-29. View Abstract
High-content live-cell imaging assay used to establish mechanism of trastuzumab emtansine (T-DM1)--mediated inhibition of platelet production. Blood. 2012 Sep 06; 120(10):1975-84. View Abstract
Does size matter in platelet production? Blood. 2012 Aug 23; 120(8):1552-61. View Abstract
Microtubule and cortical forces determine platelet size during vascular platelet production. Nat Commun. 2012 May 22; 3:852. View Abstract
The origin and function of platelet glycosyltransferases. Blood. 2012 Jul 19; 120(3):626-35. View Abstract
VEGF, PF4 and PDGF are elevated in platelets of colorectal cancer patients. Angiogenesis. 2012 Jun; 15(2):265-73. View Abstract
Visualization and manipulation of the platelet and megakaryocyte cytoskeleton. Methods Mol Biol. 2012; 788:109-25. View Abstract
Release of angiogenesis regulatory proteins from platelet alpha granules: modulation of physiologic and pathologic angiogenesis. Blood. 2011 Aug 04; 118(5):1359-69. View Abstract
The identification and characterization of zebrafish hematopoietic stem cells. Blood. 2011 Jul 14; 118(2):289-97. View Abstract
The spectrin-based membrane skeleton stabilizes mouse megakaryocyte membrane systems and is essential for proplatelet and platelet formation. Blood. 2011 Aug 11; 118(6):1641-52. View Abstract
Platelets and the immune continuum. Nat Rev Immunol. 2011 Apr; 11(4):264-74. View Abstract
Developmental differences in megakaryocytopoiesis are associated with up-regulated TPO signaling through mTOR and elevated GATA-1 levels in neonatal megakaryocytes. Blood. 2011 Apr 14; 117(15):4106-17. View Abstract
Platelets generated from human embryonic stem cells are functional in vitro and in the microcirculation of living mice. Cell Res. 2011 Mar; 21(3):530-45. View Abstract
Cytoskeletal mechanics of proplatelet maturation and platelet release. J Cell Biol. 2010 Nov 15; 191(4):861-74. View Abstract
Serum response factor is an essential transcription factor in megakaryocytic maturation. Blood. 2010 Sep 16; 116(11):1942-50. View Abstract
Junín virus infection of human hematopoietic progenitors impairs in vitro proplatelet formation and platelet release via a bystander effect involving type I IFN signaling. PLoS Pathog. 2010 Apr 15; 6(4):e1000847. View Abstract
Platelet-derived thrombospondin-1 is a critical negative regulator and potential biomarker of angiogenesis. Blood. 2010 Jun 03; 115(22):4605-13. View Abstract
The mouse mutation "thrombocytopenia and cardiomyopathy" (trac) disrupts Abcg5: a spontaneous single gene model for human hereditary phytosterolemia/sitosterolemia. Blood. 2010 Feb 11; 115(6):1267-76. View Abstract
Megakaryocyte-derived microparticles: direct visualization and distinction from platelet-derived microparticles. Blood. 2009 Jan 29; 113(5):1112-21. View Abstract
ABL2/ARG tyrosine kinase mediates SEMA3F-induced RhoA inactivation and cytoskeleton collapse in human glioma cells. J Biol Chem. 2008 Oct 03; 283(40):27230-8. View Abstract
Direct visualization of the endomitotic cell cycle in living megakaryocytes: differential patterns in low and high ploidy cells. Cell Cycle. 2008 Aug; 7(15):2352-6. View Abstract
RanBP10 is a cytoplasmic guanine nucleotide exchange factor that modulates noncentrosomal microtubules. J Biol Chem. 2008 May 16; 283(20):14109-19. View Abstract
Visualization of microtubule growth in living platelets reveals a dynamic marginal band with multiple microtubules. Blood. 2008 May 01; 111(9):4605-16. View Abstract
Role of Epac1, an exchange factor for Rap GTPases, in endothelial microtubule dynamics and barrier function. Mol Biol Cell. 2008 Mar; 19(3):1261-70. View Abstract
Angiogenesis is regulated by a novel mechanism: pro- and antiangiogenic proteins are organized into separate platelet alpha granules and differentially released. Blood. 2008 Feb 01; 111(3):1227-33. View Abstract
Platelet-associated PF-4 as a biomarker of early tumor growth. Blood. 2008 Feb 01; 111(3):1201-7. View Abstract
Dynamic visualization of thrombopoiesis within bone marrow. Science. 2007 Sep 21; 317(5845):1767-70. View Abstract
Delivering new insight into the biology of megakaryopoiesis and thrombopoiesis. Curr Opin Hematol. 2007 Sep; 14(5):419-26. View Abstract
The biogenesis of platelets from megakaryocyte proplatelets. J Clin Invest. 2005 Dec; 115(12):3348-54. View Abstract
Mechanisms of organelle transport and capture along proplatelets during platelet production. Blood. 2005 Dec 15; 106(13):4066-75. View Abstract
Differential roles of microtubule assembly and sliding in proplatelet formation by megakaryocytes. Blood. 2005 Dec 15; 106(13):4076-85. View Abstract
Elevated release of sCD40L from platelets of diabetic patients by thrombin, glucose and advanced glycation end products. Diab Vasc Dis Res. 2005 May; 2(2):81-7. View Abstract
Interactions between the megakaryocyte/platelet-specific beta1 tubulin and the secretory leukocyte protease inhibitor SLPI suggest a role for regulated proteolysis in platelet functions. Blood. 2004 Dec 15; 104(13):3949-57. View Abstract
A role for Rab27b in NF-E2-dependent pathways of platelet formation. Blood. 2003 Dec 01; 102(12):3970-9. View Abstract
The birth of the platelet. J Thromb Haemost. 2003 Jul; 1(7):1580-6. View Abstract
Role for phosphoinositide 3-kinase in Fc gamma RIIA-induced platelet shape change. Am J Physiol Cell Physiol. 2003 Oct; 285(4):C797-805. View Abstract
Megakaryocytes and beyond: the birth of platelets. J Thromb Haemost. 2003 Jun; 1(6):1174-82. View Abstract
Alpha-adducin dissociates from F-actin and spectrin during platelet activation. J Cell Biol. 2003 May 12; 161(3):557-70. View Abstract
Mechanisms and implications of platelet discoid shape. Blood. 2003 Jun 15; 101(12):4789-96. View Abstract
Importance of free actin filament barbed ends for Arp2/3 complex function in platelets and fibroblasts. Proc Natl Acad Sci U S A. 2002 Dec 24; 99(26):16782-7. View Abstract
A lineage-restricted and divergent beta-tubulin isoform is essential for the biogenesis, structure and function of blood platelets. Curr Biol. 2001 Apr 17; 11(8):579-86. View Abstract
How the assembly dynamics of the nematode major sperm protein generate amoeboid cell motility. Int Rev Cytol. 2001; 202:1-34. View Abstract
Hematopoietic-specific beta 1 tubulin participates in a pathway of platelet biogenesis dependent on the transcription factor NF-E2. Blood. 2000 Aug 15; 96(4):1366-73. View Abstract
Blood platelets are assembled principally at the ends of proplatelet processes produced by differentiated megakaryocytes. J Cell Biol. 1999 Dec 13; 147(6):1299-312. View Abstract
Localized depolymerization of the major sperm protein cytoskeleton correlates with the forward movement of the cell body in the amoeboid movement of nematode sperm. J Cell Biol. 1999 Sep 06; 146(5):1087-96. View Abstract
Amoeboid motility without actin: insights into the molecular mechanism of locomotion using the major sperm protein (MSP) of nematodes. Biol Bull. 1998 Jun; 194(3):342-3; discussion 343-4. View Abstract
Reconstitution in vitro of the motile apparatus from the amoeboid sperm of Ascaris shows that filament assembly and bundling move membranes. Cell. 1996 Jan 12; 84(1):105-14. View Abstract
In Ascaris sperm pseudopods, MSP fibers move proximally at a constant rate regardless of the forward rate of cellular translocation. Cell Motil Cytoskeleton. 1995; 31(3):241-53. View Abstract