Specialty Division

Cancer and Immunobiology

Research Expertise

The main focus of my research has been on the link between inflammation and thrombosis, with an emphasis on the pathobiology of alpha-defensins, plasminogen activator system and recently developmental endothelial locus-1 (Del-1) and its role in chronic and acute thrombo-inflammatory diseases like thrombotic stroke, acute chest syndrome (ACS) in sickle cell disease. I was among the first to characterize a transgenic mouse that expresses human alpha-defensins in its neutrophils. It has been our underlying hypothesis that the lack of alpha-defensins in mouse neutrophils, the most abundant protein secreted by their activated human counterparts, together with the rapid apoptosis that these cells undergo in tissue, has led to an under-appreciation of their role in inflammatory and thrombotic disorders. I have extensive experience in the production, purification and characterization of human alpha defensins and Del-1 and diverse in vivo animal models of thrombosis, pulmonary embolism, acute lung injury, and ischemic stroke. My recent focus is the role of Del-1 as a pulmonary endothelial cell derived negative regulator of inflammation in the pathogenesis of ACS. My collaborators provided me with Del-1 knock out and over-expressors mice, and I have generated a novel CRISPR mouse with a single amino acid mutation essential for integrin binding and function of Del-1.

Itmat Expertise

Dr. Bdeir studies the role of plasminogen activators and neutrophil-defensins in the development of atherosclerosis, angiogenesis and acute lung injury and the mechanism of these effects using in-vitro and in-vivo models that will potentially lead to translational therapy.

Education

B.Sc.Pharm (Pharmacy), Hebrew University of Jerusalem, School of Pharmacy, Jerusalem, Israel, 1987
M.Sc.Pham (Pharmacokinetics and Pharmacodynamics), Hebrew University of Jerusalem, School of Pharmacy, Jerusalem, Israel, 1990
PhD (Biochemistry and Pharmacology), Hebrew University of Jerusalem, Hadassah Medical School, Jerusalem, Israel, 1996

Specialty Certification

Postgraduate Training

Post-doctoral Researcher, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 1996-98

Awards and Honors

Medical Faculty Prize for Distinction in M.Sc. Research, Hebrew University, Israel, 1989
American Heart Association Pennsylvania & Delaware Affiliate Award for Outstanding Effort in the Area of Research and Education in the Fight Against Heart Diseases and Stroke, 2001

Memberships and Professional Organizations

American Heart Association, 2004-present
American Stroke Association, 2006-present
International Society for Fibrinolysis & Proteolysis (ISFP), 2006-09
International Society on Thrombosis and Haemostasis (ISTH), 2007-present
Society for Leukocyte Biology (SLB), 2008-present
American Thoracic Society (ATS), 2009-present
National Institutes of Health (NIH), 2016

Web Links

Selected Publications

Modulation of ultralarge immune complexes in heparin-induced thrombocytopenia
Cai Z, Bdeir K, Yarovoi SV, Rauova L, Arepally GM, Khandelwal S, Rollin J, Gruel Y, Zaitsev S, Poncz M, Greene MI, Cines DB. J Thromb Haemost 21(3):652-666, Mar 2023. doi: 10.1016/j.jtha.2022.11.043. Epub 2022 Dec 22. PMID: 36696211. 

Human neutrophil peptides 1-3 protect the murine urinary tract from uropathogenic Escherichia coli challenge 
Canas JJ, Liang D, Saxena V, Hooks J, Arregui SW, Gao H, Liu Y, Kish D, Linn SC, Bdeir K, Cines DB, Fairchild RL, Spencer JD, Schwaderer AL, Hains DS. Proc Natl Acad Sci U S A 119(40):e2206515119, Oct 2022. doi: 10.1073/pnas.2206515119. Epub 2022 Sep 26. PMID: 36161923. 

Divergent impacts of tocilizumab and colchicine in COVID-19-associated coagulopathy: the role of alpha-defensins 
Abdeen S, Abu-Fanne R, Bdeir K, Maraga E, Higazi M, Cines DB, Heyman SN, Higazi AA. Br J Haematol 196(4):923-927, Feb 2022. doi: 10.1111/bjh.17885. Epub 2021 Oct 27. PMID: 34622440. 

Alpha-defensins: risk factor for thrombosis in COVID-19 infection 
Abdeen S, Bdeir K, Abu-Fanne R, Maraga E, Higazi M, Khurram N, Feldman M, Deshpande C, Litzky LA, Heyman SN, Montone KT, Cines DB, Higazi AA. Br J Haematol 194(1):44-52, Jul 2021. doi: 10.1111/bjh.17503. Epub 2021 May 30. PMID: 34053084. 

The DEL-1/β3 integrin axis promotes regulatory T cell responses during inflammation resolution 
Li X, Colamatteo A, Kalafati L, Kajikawa T, Wang H, Lim JH, Bdeir K, Chung KJ, Yu X, Fusco C, Porcellini A, De Simone S, Matarese G, Chavakis T, De Rosa V, Hajishengallis G. J Clin Invest 130(12):6261-6277, Dec 2020. doi: 10.1172/JCI137530. PMID: 32817592. 

The secreted protein DEL-1 activates a β3 integrin-FAK-ERK1/2-RUNX2 pathway and promotes osteogenic differentiation and bone regeneration
Yuh DY, Maekawa T, Li X, Kajikawa T, Bdeir K, Chavakis T, Hajishengallis G. J Biol Chem 295(21):7261-7273, May 2020. doi: 10.1074/jbc.RA120.013024. Epub 2020 Apr 12. PMID: 32280065. 

Opposing effects of HNP1 (α-defensin-1) on plasma cholesterol & atherogenesis
Higazi M, Abdeen S, Abu-Fanne R, Heyman SN, Masarwy A, Bdeir K, Maraga E, Cines DB, Higazi AA. PLoS One 15(4):e0231582, Apr 2020. doi: 10.1371/journal.pone.0231582. PMID:32302327. 

Human neutrophil peptide-1 inhibits thrombus formation under arterial flow via its terminal free cysteine thiols
McDaniel JK, Abdelgawwad MS, Hargett A, Renfrow MB, Bdeir K, Cao W, Cines DB, Zheng XL. J Thromb Haemost 17(4):596-606, Apr 2019. doi: 10.1111/jth.14407. Epub 2019 Mar 13. PMID: 30741476. 

Neutrophil α-defensins promote thrombosis in vivo by altering fibrin formation, structure, and stability
Abu-Fanne R, Stepanova V, Litvinov RI, Abdeen S, Bdeir K, Higazi M, Maraga E, Nagaswami C, Mukhitov AR, Weisel JW, Cines DB, Higazi AA. Blood 133(5):481-493, Jan 2019. doi: 10.1182/blood-2018-07-861237. Epub 2018 Nov 15. PMID: 30442678. 

Human Neutrophil Peptide 1 Limits Hypercholesterolemia-induced Atherosclerosis by Increasing Hepatic LDL Clearance
Paulin N, Döring Y, Kooijman S, Blanchet X, Viola JR, de Jong R, Mandl M, Hendrikse J, Schiener M, von Hundelshausen P, Vogt A, Weber C, Bdeir K, Hofmann SM, Rensen PCN, Drechsler M, Soehnlein O. EBioMedicine 16:204-211, Feb 2017. doi: 10.1016/j.ebiom.2017.01.006. Epub 2017 Jan 7. PMID: 28111237.