Dr Freda Passam

Clinical Academic Haematologist, Royal Prince Alfred Hospital, Heart Research Institute &
Charles Perkins Centre


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Biographical details

Dr. Freda Passam leads the Haematology Research Group in the Heart Research Institute/Charles Perkins Centre of the University of Sydney focused on basic and translational research in thrombotic disease. She is a clinical academic haematologist in the Royal Prince Alfred Hospital, Sydney, with a special interest in thrombosis and haemostasis. Dr Passam received her medical degree and PhD in Greece on the role of angiogenesis in Hodgkin's lymphoma. She trained in clinical and laboratory Haematology, initially in Greece and then in Sydney. Her postdoctoral research was on the pathophysiology ofthe antiphospholipid syndromein the University of New South Wales followed by studies on animal models of thrombosis in Harvard University, Boston, USA. Dr Passam returned to Sydney in 2013 as a haematologist at St George Hospital and Senior Lecturer in Medicine at UNSW. She joined the RPA Hospital and the University of Sydney in 2018. Dr Passam’s research has identified a group of clotting enzymes, named thiol isomerases, that have potential as novel antithrombotic targets. Her research group has detected post-translational modifications of integrins that control platelet function. The Haematology Research group also has a keen interest in the application of microfluidic devices for the diagnosis of thrombotic and bleeding tendency in patients.

Research interests

Integrin biology

Functional disulphides

Platelets

Antiphospholipid syndrome

Animal models of thrombosis

Microfluidic devices

Teaching and supervision

Haematology

Coagulation & Haemostasis

Bleeding & Thrombotic Disorders

Current projects

1. Control of integrin function by functional disulphides

The purpose of this study is to understand how post-translational modifications of integrin disulphide bonds control cell function and thrombus formation.

2. Thiol isomerases as novel antithrombotic targets

We have identified a novel clotting enzymes, named thiol isomerases. Inhibitors of these enzymes can be developed into drugs that treat thrombotic disease.

3. Biochips for the assessment of haemostasis and thrombosis

Using biochips in a microfluidic system that simulates human circulation, we aim to detect thrombotic or bleeding tendency in patient samples.

Awards and honours

2018: Sydney Cardiovascular Fellowship

2016-2018: Kanematsu Novo Nordisk Award, RCPA

2016-2017: St George & Sutherland Medical Research Foundation, Seed Grant

2015-2016: UNSW Goldstar Award

2013-2014: St George Medical Research Foundation, New Investigator Award

2009-2011: International Research Award from the American Society of Haematology

2007-2008: Postdoctoral Research Award by the Foundation of the Greek Society of Haematologists

In the media

https://twitter.com/hashtag/ramaciottiawards2017

Publications:

1. Bekendam RH, Iyu D, Passam F, Stopa JD, De Ceunynck K, Muse O, Bendapudi PK, Garnier CL, Gopal S, Crescence L, Chiu J, Furie B, Panicot-Dubois L, Hogg PJ, Dubois C, Flaumenhaft R.Protein disulfide isomerase regulation by nitric oxide maintains vascular quiescence and controls thrombus formation. J Thromb Haemost. 2018 Sep 12

2. Passam F, Chiu J, Ju L, Pijning A, Jahan Z, Mor-Cohen R, Yeheskel A, Kolšek K, Thärichen L, Aponte-Santamaría C, Gräter F, Hogg PJ. Mechano-redox control of integrin de-adhesion. Elife. 2018 Jun 22;7

3. Lee KH, Cavanaugh L, Leung H, Yan F, Ahmadi Z, Chong BH, Passam F. Quantification of NETs-associated markers by flow cytometry and serum assays in patients with thrombosis and sepsis. Int J Lab Hematol. 2018 Mar 9

4. Butera D, Passam F, Ju L, Cook KM, Woon H, Aponte-Santamaría C, Gardiner E, Davis AK, Murphy DA, Bronowska A, Luken BM, Baldauf C, Jackson S, Andrews R, Gräter F, Hogg PJ. Autoregulation of von Willebrand factor function by a disulfide bond switch. Sci Adv. 2018 Feb 28;4(2)

5.El-Assaad F, Qi M, Gordon AK, Qi J, Dong S, Passam F, Weaver JC, Giannakopoulos B, Krilis SA. Βeta 2-glycoprotein I protects mice against gram-negative septicaemia in a sexually dimorphic manner. Sci Rep. 2017;7:8201.1

6.Chiu J, Passam F, Butera D, Hogg PJ. Protein Disulfide Isomerase in Thrombosis. Semin Thromb Hemost. 2015;41:765-773

7.Lin L, Gopal S, Sharda A, Passam F, Bowley SR, Stopa J, Xue G, Yuan C, Furie BC, Flaumenhaft R, Huang M, Furie B. Quercetin-3-rutinoside Inhibits Protein Disulfide Isomerase by Binding to Its b'x Domain. J Biol Chem. 2015;290:23543-23552

8.Passam FH, Lin L, Gopal S, Stopa J, Bellido-Martin L, Huang M, Furie BC, Furie B. Both platelet- and endothelial cell-derived ERp5 supports thrombus formation in a laser-induced mouse model of thrombosis. Blood. 2015;125:2276-2285

9.Khodier C, VerPlank L, Nag PP, Pu J, Wurst J, Pilyugina T, Dockendorff C, Galinski CN, Scalise AA, Passam F, van Hessem L, Dilks J, Kennedy DR, Flaumenhaft R, Palmer MAJ, Dandapani S, Munoz B, Schrieber SL. Identification of ML359 as a Small Molecule Inhibitor of Protein Disulfide Isomerase. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-2013 Apr 12 [updated 2014 Sep 18].

10.Jasuja R, Passam FH, Kennedy DR, Kim S, van Hessem L, Lin L, Joshi SS, Dilks DR, Furie B, Furie BC, Flaumenhaft R. Protein disulfide isomerase inhibitors: A new class of antithrombotic agents. J Clin Invest. 2012; 122:2104-2113

11.Owens AP 3rd, Passam FH, Antoniak S, Marshall SM, McDaniel AL, Rudel L, Williams JC, Hubbard BK, Dutton JA, Wang J, Tobias PS, Curtiss LK, Daugherty A, Kirchhofer D, Luyendyk JP, Moriarty PM, Nagarajan S, Furie BC, Furie B, Johns DG, Temel RE, Mackman N. Monocyte tissue factor-dependent activation of coagulation in hypercholesterolemic mice and monkeys is inhibited by simvastatin. J Clin Invest. 2012; 122:558-568

12.Passam FH, Giannakopoulos B, Mirarabshahi P, Krilis SA. Molecular pathophysiology of the antiphospholipid syndrome: the role of oxidative post-translational modification of beta 2 glycoprotein I. J Thromb Haemost. 2011;9 Suppl 1:275-282

13.Passam FH, Rahgozar S, Qi M,Raftery MJ Wong JWH,Tanaka K, Ioannou Y, Zhang JY, Gemmell R, Qi JC, Giannakopoulos B, Hughes WE, Hogg PJ, Krilis SA. Redox control of β2-glycoprotein I-von Willebrand factor interaction by thioredoxin-1. J Thromb Haemost 2010;8(8):1754-1762

14.Passam FH, Qi JC, Tanaka K, Matthaei KI, Krilis SA. In vivo modulation of angiogenesis by beta 2 glycoprotein I. J Autoimmun. 2010;35:232-240

15.Passam FH, Rahgozar S, Qi M, Raftery MJ, Wong JWH, Tanaka K, Ioannou Y, Zhang JY, Gemmell R, Qi JC, Hughes WE, Giannakopoulos B, Hogg PJ, Krilis SA. Beta 2 glycoprotein I is a substrate of thiol oxidoreductases. Blood 2010;116:1995-1997

16.Ioannou Y, Zhang JY, Passam FH, Rahgozar S, Qi JC, Giannakopoulos B, Qi M, Pei Y, Yu DM, Hogg PJ, Krilis SA. Naturally occurring free thiols within ß2-glycoprotein I in vivo: nitrosylation, redox modification by endothelial cells and regulation of oxidative stress induced cell injury. Blood 2010;116:1961-1970

17.Giannakopoulos B, Passam F, Ioannou Y, Krilis SA. How we diagnose the antiphospholipid syndrome. Blood 2009;113:985-994

18.Passam FH, Alexandrakis MG, Kafousi M, Fotinou M, Darivianaki K, Tsirakis G, Roussou PA, Stathopoulos EN, Siafakas NM. Histological expression of angiogenic factors: VEGF, PDGFRα and HIF-1α in Hodgkin lymphoma. Pathol Res Pract 2009;205:11-20

19.Yu P, Passam FH, Yu DM, Denyer G, Krilis SA. β2-glycoprotein I inhibits vascular endothelial growth factor and basic fibroblast growth factor induced angiogenesis through its amino terminal domain. J Thromb Haemost 2008;6:1215-1223

20.Passam FH, Sfiridaki A, Pappa C, Kyriakou D, Petreli E, Roussou PA, Alexandrakis MG. Angiogenesis related growth factors and cytokines in the serum of patients with B-Non Hodgkin Lymphoma; relation to clinical features and response to treatment. Int J Lab Haem 2008;30:17-25

21.Giannakopoulos B, Passam F, Rahgozar S, Krilis SA. Current concepts on the pathogenesis of the antiphospholipid syndrome. Blood 2007;109:422-430

22.Passam F, Tachynopoulou V, Skoumi D, Tsompanakou A, Stavropoulos-Giokas A, Vadikolia C, Anagnostopoulos A, Paterakis G. Feasibility of an easy applicable method of ZAP-70 measurement in chronic lymphocytic leukemia in the routine flow cytometry setting: a methodological approach. Ann Hematol 2006;85:795-805

23.Passam FH, Alexandrakis MG, Moschandrea J, Sfiridaki A, Roussou PA, Siafakas NM. Angiogenic molecules in Hodgkin's disease: results from sequential serum analysis. Int J Immunopathol Pharmacol 2006;19:759-768

24.Passam FH, Diamantis ID, Perisinaki G, Saridaki Z, Kritikos H, Georgopoulos D, Boumpas DT. Intestinal ischemia as the first manifestation of vasculitis. Semin Arthritis Rheum 2004;34:431-441

International links

United States

(Harvard Medical School, Boston, USA Professor Rob Flaumenhaft) Project: Thiol isomerase inhibitors as novel antithrombotics

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