Dr Jose Sail Perdomo
Research Fellow

Dr Jose Sail Perdomo

medicine-health
St. George Clin Sch- Operating

Dr Jose Perdomo is a Research Fellow at the Haematology Research Unit, St George & Sutherland Clinical School, UNSW. Dr Perdomo’s broad research areas are in: Haematology and Stem Cells, Vascular Biology and Thrombosis, Antibody Engineering, Cell Biology and Gene Regulation.

Dr Perdomo's interests include elucidation of the mechanisms that lead to immune thrombocytopenia (low platelet counts) (ITP) and drug-induced thrombocytopenia (DITP). Low platelet numbers can result in internal bleeding and even death. Several prescription drugs produce immune reactions that lead to the production of drug-dependent antibodies that cause platelet damage. Similar antibodies that cause low platelet counts are produced in autoimmune conditions such as ITP. His research has found that these auto-antibodies do not only damage circulating platelets but also their cellular precursors (called megakaryocytes). Affected megakaryocytes show diminished platelet production capacity.

He is currently investigating the cellular and molecular mechanisms by which antibodies cause platelet destruction using humanized mouse models, including the role of the gut microbiome in the pathogenesis of this autoimmune conditoins. This research is contributing to a more complete understanding of the pathogenesis of immune thrombocytopenia. Recent findings show that the liver is involved in platelet destruction. Experiments in mice have shown that this destruction can be prevented using an existing drug.

Another important area of research is heparin-induced thrombocytopenia and thrombosis (HIT). HIT is a serious antibody-mediated condition developed by many patients undergoing heparin treatment (eg, during surgery). HIT is characterised by low platelet numbers and clot formation. Clots can form anywhere. For instance, clotting in the legs produces gangrene, which often results in amputation. The death rate from HIT is still unacceptably high. Current therapies are limited and a therapy the stops HIT in affected patients is urgently needed.

Recently he found that central components in HIT-induced clotting are white cells (called neutrophils). They promote clot formation by releasing their DNA in a process known as neutrophil extracellular trap formation. This DNA then forms a scaffold that traps other cells and leads to clot formation. This is a key finding in the pathology of HIT, since until now it was thought that clot formation was due platelet activation. This has significant consequences for the development of treatments for this serious clotting condition.

An antibody fragment that counteracts the effect of the HIT antibodies has been designed and has been successfully tested in our laboratory and in a mouse model of HIT, with remarkable results. The activity of this novel molecule will stop the action of the HIT antibody thus preventing the progression this condition.

Antibody engineering research has also led to the development of a bi-specific molecule (a molecule with two distinct functions) that interacts with activated platelets (ie, those found at the sites of clotting) and inhibits platelet aggregation and clot formation. This bi-specific molecule is active in mice and is being developed as an antithrombotic targeted drug.

Specific Research Keywords: Molecular Haematopoiesis, Neutrophil extracellular traps, NETosis, Drug-induced Thrombocytopenia, Immune Thrombocytopenia, Vascular Biology, Thrombosis

 

Phone
+61 2 9113 1915
Location
St George & Sutherland Clinical School Haematology Research Unit Research and Education Centre St George Hospital 4-10 South St Kogarah, NSW 2217

Publications

  • Book Chapters | 2018
    Dr Jose Sail Perdomo
    Perdomo JS, 2018, 'Advances in the Understanding and Treatment of Immune Thrombocytopenia', in Frontiers in Clinical Drug Research-Hematology volume: 3, Bentham eBooks, Sharjah, UAE, pp. 1 - 28, http://dx.doi.org/10.2174/97816810836741180301
    Book Chapters | 2005
    Dr Jose Sail Perdomo
    Verger A; Perdomo JS; Crossley M, 2005, 'CtBP and Hematopoietic Transcriptional Regulators', in Chinnadurai G (ed.), CtBP Family Proteins, edn. Original, Landes Bioscience/Eurekah.com, Georgetown, Tex., pp. 28 - 38
  • Journal articles | 2021
    Dr Jose Sail Perdomo
    Zheng SS; Perdomo JS; Ahmadi Z; Chong BH, 2021, 'Indirect detection of anti-platelet antibodies in immune thrombocytopenia', Pathology, http://dx.doi.org/10.1016/j.pathol.2020.12.006
    Journal articles | 2021
    Dr Jose Sail Perdomo
    Rashid FN; Clayton ZE; Ogawa M; Perdomo J; Hume R; Kizana E; Chong JJH, 2021, 'Platelet derived growth factor-A (Pdgf-a) gene transfer modulates scar composition and improves left ventricular function after myocardial infarction.', Int J Cardiol, http://dx.doi.org/10.1016/j.ijcard.2021.07.021
    Journal articles | 2020
    Dr Jose Sail Perdomo
    Perdomo J, 2020, 'Untying knots to make more platelets', Blood, vol. 136, pp. 1702 - 1703, http://dx.doi.org/10.1182/blood.2020007381
    Journal articles | 2020
    Dr Jose Sail Perdomo
    Zheng SS; Perdomo JS; Leung HHL; Yan F; Chong BH, 2020, 'Acquired Glanzmann thrombasthenia associated with platelet desialylation', Journal of Thrombosis and Haemostasis, vol. 18, pp. 714 - 721, http://dx.doi.org/10.1111/jth.14722
    Journal articles | 2019
    Dr Jose Sail Perdomo
    Perdomo J; Leung HHL; Ahmadi Z; Yan F; Chong JJH; Passam FH; Chong BH, 2019, 'Neutrophil activation and NETosis are the major drivers of thrombosis in heparin-induced thrombocytopenia', Nature Communications, vol. 10, pp. 1322, http://dx.doi.org/10.1038/s41467-019-09160-7
    Journal articles | 2019
    Dr Jose Sail Perdomo
    Ahmadi Z; Perdomo J; Wong R; Chong BH, 2019, 'Drug-induced immune thrombocytopenia: Mapping of the drug binding site to the membrane-proximal region of platelet GPIX', Platelets, vol. 30, pp. 251 - 255, http://dx.doi.org/10.1080/09537104.2017.1419556
    Journal articles | 2018
    Dr Jose Sail Perdomo
    Perdomo J, 2018, 'Antiplatelet Autoantibodies Inhibit Proplatelet Formation by Megakaryocytes and Impair Platelet Production in vitro', Journal of Immunological Sciences, vol. 6, pp. 1 - 3, http://dx.doi.org/10.29245/2578-3009/2018/6.1163
    Journal articles | 2017
    Dr Jose Sail Perdomo
    Perdomo JS; Yan F; Leung HH; Chong BH, 2017, 'Megakaryocyte Differentiation and Platelet Formation from Human Cord Blood-derived CD34+ Cells', Journal of Visualized Experiments, vol. 2017, http://dx.doi.org/10.3791/56420
    Journal articles | 2016
    Dr Jose Sail Perdomo
    Perdomo J, 2016, 'Role of romiplostim in splenectomized and nonsplenectomized patients with immune thrombocytopenia', ImmunoTargets and Therapy, vol. 5, pp. 1 - 7, http://dx.doi.org/10.2147/ITT.S80648
    Journal articles | 2015
    Dr Jose Sail Perdomo
    Iraqi M; Perdomo J; Yan F; Choi PYI; Chong BH, 2015, 'Immune thrombocytopenia: Antiplatelet autoantibodies inhibit proplatelet formation by megakaryocytes and impair platelet production in vitro', Haematologica, vol. 100, pp. 623 - 632, http://dx.doi.org/10.3324/haematol.2014.115634
    Journal articles | 2014
    Dr Jose Sail Perdomo
    Carter DR; Buckle AD; Tanaka K; Perdomo J; Chong BH, 2014, 'Art27 interacts with GATA4, FOG2 and NKX2.5 and is a novel co-repressor of cardiac genes', PLoS ONE, vol. 9, http://dx.doi.org/10.1371/journal.pone.0095253
    Journal articles | 2013
    Dr Jose Sail Perdomo
    Chong BH; Choi PY; Khachigian LM; Perdomo JS, 2013, 'Drug-induced immune thrombocytopenia', Hematology - Oncology Clinics of North America, vol. 27, pp. 521 - 540, http://dx.doi.org/10.1016/j.hoc.2013.02.003
    Journal articles | 2013
    Dr Jose Sail Perdomo
    Perdomo JS; Yan F; Chong BH, 2013, 'A megakaryocyte with no platelets: Anti-platelet antibodies, apoptosis, and platelet production.', Platelets, vol. 24, pp. 98 - 106, http://dx.doi.org/10.3109/09537104.2012.669508
    Journal articles | 2012
    Dr Jose Sail Perdomo
    Perdomo J; Jiang X-M; Carter DR; Khachigian LM; Chong BH, 2012, 'SUMOylation Regulates the Transcriptional Repression Activity of FOG-2 and Its Association with GATA-4', PLoS ONE, vol. 7, pp. e50637 - e50637, http://dx.doi.org/10.1371/journal.pone.0050637
    Journal articles | 2012
    Dr Jose Sail Perdomo
    Funnell AP; Norton LJ; Mak KS; Burdach J; Artuz CM; Twine NA; Wilkins MR; Power C; Hung TT; Perdomo JS; Bell-Anderson K; Orkin SH; Pearson RC; Crossley M, 2012, 'The CACCC-binding protein KLF3/BKLF represses a subset of KLF1/EKLF target genes and is required for proper erythroid maturation in vivo', Molecular and Cellular Biology, vol. 32, pp. 3281 - 3292, http://dx.doi.org/10.1128/MCB.00173-12
    Journal articles | 2011
    Dr Jose Sail Perdomo
    Perdomo JS; Yan F; Ahmadi Z; Jiang XM; Stocker R; Chong BH, 2011, 'Quinine-induced thrombocytopenia: drug-dependent GPIb/IX antibodies inhibit megakaryocyte and proplatelet production in vitro', Blood, vol. 117, pp. 5975 - 5986, http://dx.doi.org/10.1182/blood-2010-10-314310
    Journal articles | 2011
    Dr Jose Sail Perdomo
    Perdomo JS; Yan F; Ahmadi Z; Jiang X-M; Chong BH, 2011, 'Quinine-induced thrombocytopenia: drug-dependent antibodies inhibit megakaryocyte and proplatelet production', JOURNAL OF THROMBOSIS AND HAEMOSTASIS, vol. 9, pp. 322 - 322, http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000208992800220&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=891bb5ab6ba270e68a29b250adbe88d1
    Journal articles | 2010
    Dr Jose Sail Perdomo
    Perdomo JS; Fock E; Kaur G; Yan F; Khachigian LM; Jans D; Chong BH, 2010, 'A monopartite sequence is essential for p45 NF-E2 nuclear translocation, transciptional activity and platelet production', Journal of Thrombosis and Haemostasis, vol. 8, pp. 2542 - 2553, http://dx.doi.org/10.1111/j.1538-7836.2010.04058.x
    Journal articles | 2007
    Dr Jose Sail Perdomo
    Kwok JC; Perdomo JS; Chong BH, 2007, 'Identification of a monopartite sequence in PU.1 essential for nuclear import, DNA-binding and transcription of myeloid-specific genes', Journal of Cellular Biochemistry, vol. 101, pp. 1456 - 1474, http://dx.doi.org/10.1002/jcb.21264
    Journal articles | 2006
    Dr Jose Sail Perdomo
    Quinlan KG; Verger A; Kwok A; Lee SH; Perdomo JS; Nardini M; Bolognesi M; Crossley M, 2006, 'Role of the C-terminal binding protein PXDLS motif binding cleft in protein interactions and transcriptional repression', Molecular and Cellular Biology, vol. 26, pp. 8202 - 8213, http://dx.doi.org/10.1128/MCB.00445-06
    Journal articles | 2005
    Dr Jose Sail Perdomo
    Perdomo JS; Verger A; Turner J; Crossley M, 2005, 'Role for SUMO modification in facilitating transcriptional repression by BKLF', Molecular and Cellular Biology, vol. 25, pp. 1549 - 1559, http://dx.doi.org/10.1128/MCB.25.4.1549-1559.2005
    Journal articles | 2004
    Dr Jose Sail Perdomo
    Westman BJ; Perdomo JS; Matthews JM; Mackay JP; Crossley M, 2004, 'Structural studies on a protein-binding zinc-finger domain of Eos reveal both similarities and differences to classical zinc fingers', Biochemistry, vol. 43, pp. 13318 - 13327, http://dx.doi.org/10.1021/bi049506a
    Journal articles | 2003
    Dr Jose Sail Perdomo
    Verger A; Perdomo JS; Crossley M, 2003, 'Modification with SUMO: A Role in Transcriptional Regulation', EMBO Reports, vol. 4, pp. 137 - 142, http://dx.doi.org/10.1038/sj.embor.embor738
    Journal articles | 2003
    Dr Jose Sail Perdomo
    Westman BJ; Perdomo JS; Crossley M; Sunde M; Mackay JP, 2003, 'The C-terminal domain of Eos forms a high-order complex in solution', The Journal of Biological Chemistry, vol. 278, pp. 42419 - 42426, http://dx.doi.org/10.1074/jbc.M306817200
    Journal articles | 2002
    Dr Jose Sail Perdomo
    Perdomo JS, 2002, 'The Ikaros family protein Eos associates with C-terminal-binding protein corepressors', European Journal of Biochemistry, vol. 269, pp. 5885 - 5892, http://dx.doi.org/10.1046/j.1432-1033.2002.03313.x
    Journal articles | 2000
    Dr Jose Sail Perdomo
    Perdomo JS, 2000, 'Eos and Pegasus, Two Members of the Ikaros Family of Proteins with Distinct DNA Binding Activities', The Journal of Biological Chemistry, vol. 275, pp. 38347 - 38354, http://dx.doi.org/10.1074/jbc.M005457200
  • Conference Abstracts | 2019
    Dr Jose Sail Perdomo
    Perdomo J; Leung HHL; Ahmadi Z; Yan F; Passam F; Chong B, 2019, 'Thrombosis in Heparin-induced Thrombocytopenia Is Mediated by Neutrophils', in Research and Practice in Thrombosis and Haemostasis, Wiley, Melbourne, Australia, presented at XXVII Congress of the International Society on Thrombosis and Haemostasis, Melbourne, Australia, 06 July 2019 - 10 July 2019, http://dx.doi.org/10.1002/rth2.12227
    Conference Abstracts | 2019
    Dr Jose Sail Perdomo
    Zheng S; Perdomo J; Chong B, 2019, 'Anti Platelet Antibodies Predict Platelet Desialylation and Apoptosis in ITP', in Research and Practice in Thrombosis and Haemostasis, Wiley, Melbourne, Australia, presented at XXVII Congress of the International Society on Thrombosis and Haemostasis, Melbourne, Australia
    Conference Abstracts | 2019
    Dr Jose Sail Perdomo
    Leung H; Perdomo J; Ahmadi Z; Yan F; Chong B, 2019, 'Dissecting the Mechanisms of Thrombocytopenia and Thrombosis in HIT', in Research and Practice in Thrombosis and Haemostasis, Wiley, presented at International Society on Thrombosis and Haemostasis
    Conference Abstracts | 2018
    Dr Jose Sail Perdomo
    Choi P; Tanaka K; Perdomo J; Chong B, 2018, 'Nucleic Acids Interfere with PF4 Tetramer Formation and Stabilise PF4 Monomers to Bind Non-Pathogenic HIT Antibodies: Subtypes of Non-Pathogenic Antibodies Emerge', in Blood, American Society of Hematology, San Diego, CA, presented at 60th meeting of the American Society of Hematology, San Diego, CA, 01 December 2018 - 04 December 2018, http://dx.doi.org/10.1182/blood-2018-99-117826
    Conference Papers | 2018
    Dr Jose Sail Perdomo
    Perdomo J, 2018, 'Neutrophil Activation and Netosis Are the Key Drivers of Thrombosis in Heparin-Induced Thrombocytopenia', in blood, American Society of Hematology, San Diego, CA, presented at 60th meeting of the American Society of Hematology, San Diego, CA, 01 December 2018 - 04 December 2018, http://dx.doi.org/10.1182/blood-2018-99-116421
    Conference Abstracts | 2015
    Dr Jose Sail Perdomo
    Perdomo J; New JY; Ahmadi Z; Jiang X-M; Chong BH, 2015, 'A Humanized Anti Fc gamma RIIa Scfv Inhibits Platelet Activation, Aggregation and Thrombus Formation in Heparin-Induced Thrombocytopenia (HIT)', in BLOOD, AMER SOC HEMATOLOGY, Orlando, FL, Vol. 126, presented at 57th Annual Meeting of the American-Society-of-Hematology, Orlando, FL, 05 December 2015 - 08 December 2015, http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000368019000074&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=891bb5ab6ba270e68a29b250adbe88d1
    Conference Papers | 2012
    Dr Jose Sail Perdomo
    New JY; Perdomo J; Jiang X-M; Chong B, 2012, 'Heparin-Induced Thrombocytopenia and Thrombosis: Therapeutic Strategy Using a Single-Chain Variable Fragment (scFv) Antibody', in BLOOD, AMER SOC HEMATOLOGY, Atlanta, GA, presented at 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH), Atlanta, GA, 08 December 2012 - 11 December 2012, http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000313838903249&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=891bb5ab6ba270e68a29b250adbe88d1
    Conference Posters | 2011
    Dr Jose Sail Perdomo
    Lim SM; Perdomo JS; Galettis P; Links MJ, 2011, 'Antiangiogenic effect of low-dose paclitaxel is mediated by RhoA inactivation: A potential new mechanism', Philadelphia, PA, USA, presented at International Conference: Molecular Targets and Cancer Therapeutics, San Francisco, CA, 12 November 2011 - 16 November 2011, http://dx.doi.org/10.1158/1535-7163.TARG-11-A4
    Conference Abstracts | 2011
    Dr Jose Sail Perdomo
    Perdomo JS; Yan F; Ahmadi Z; Jiang X; Chong B, 2011, 'Quinine-induced thrombocytopenia: drug-dependent antibodies inhibit megakaryocyte and proplatelet production', in Journal of Thrombosis and Haemostasis, Wiley, Kyoto, presented at XXIII Congress of the International Society on Thrombosis and Haemostasis, Kyoto, 23 July 2011 - 28 July 2011
    Conference Papers | 2010
    Dr Jose Sail Perdomo
    Perdomo J; Yan F; Ahmadi Z; Jiang X-M; Chong B, 2010, 'Proplatelet Production Is Impaired by Drug-Induced Thrombocytopenia Antibodies', in BLOOD, AMER SOC HEMATOLOGY, Orlando, FL, pp. 173 - 173, presented at 52nd Annual Meeting of the American-Society-of-Hematology (ASH), Orlando, FL, 04 December 2010 - 07 December 2010, http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000289662200385&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=891bb5ab6ba270e68a29b250adbe88d1
    Conference Papers | 2010
    Dr Jose Sail Perdomo
    Perdomo JS; Yan F; Ahmadi Z; Jiang X; Chong BH, 2010, 'Proplatelet Production Is Impaired by Drug-Induced Thrombocytopenia Antibodies', in Broze G (ed.), Blood, American Society of Hematology, USA, pp. 384, presented at Annual Meeting of the American Society of Hematology, Orlando, Florida, - , http://abstracts.hematologylibrary.org/cgi/citmgr?gca=ashmtg;116/21/384

Awards

Grants

The role of neutrophils in the pathology of immune thrombocytopenia, RESEARCH GRANT, CI: Perdomo, J. Funding agency: ST GEORGE & SUTHERLAND MEDICAL RESEARCH FOUNDATION, 2019

 

impact of gut microbiota metabolites on the development of thrombosis, thrombocytopenia and increased cardiovascular risk in autoimmune/inflammatory disorders and infection: the role of trimethylamine n-oxide-induced platelet hyperactivityRESEARCH GRANT, CIB: Perdomo, J. Funding agency: ST GEORGE & SUTHERLAND MEDICAL RESEARCH FOUNDATION, 2018

 

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