Faculty Contact Info

OFFICE:  909 S Wolcott

              5095 COMRB

PH #:  (312) 335-5923

EMAIL:  thromres@uic.edu


LAB PAGE​​​​​​​

Jaehyung (Gus) Cho, PhD

ASSOCIATE PROFESSOR OF MEDICINE AND PHARMACOLOGY

Research Interests

The basic question that drives my research is: how are thrombosis and inflammation intertwined? Current projects focus on understanding the mechanisms mediating intravascular cell-cell interaction following vascular injury.


1.   Role of cell surface protein disulfide isomerase (PDI) and its regulator in thrombosis and vascular inflammation.


A newly-developed hypothesis is that important steps in the process of thrombosis and inflammation are regulated by the oxidation or reduction state of labile disulfide bones in hemostatis and adhesive proteins. Using PDI conditional knockout (CKO) mice developed by use, we demonstrated that the isomerase activity of platelet surface PDI is required for the full activation of αIIbβ3 integrin and platelet accumulation at the site of arterial injury without affecting hemostasis (Kim et al. Blood 2013). Further, we found that the activity of neutrophil surface PDI regulates the ligand-binding function of αMβ2 integrin and neutrophil recruitment during vascular inflammation (Hahm et al. Blood 2013). Using pharmacological and genetic approaches, we will continue to determine the physiological role of extracellular thiol isomerases and their oxidases in regulating platelet and neutrophil functions during thrombosis and vascular inflammation.


2.   Role of AKT and NOXs signaling in mediating cell-cell interactions under thromboinflammatory conditions.


Real-time intravital microscopy has provided evidence that neutrophil-platelet interactions on the activated ECs mediate microvascular occlusion under thromboinflammatory conditions. Although the major receptors and their ligands required for the cell-cell association have been well identified, it remains poorly understood how the receptor-ligand interaction is regulated during vascular diseases. We demonstrated that AKT2 and NADPH oxidase 2 (NOX2) are critical for regulating the function of key receptors, including αMβ2 integrin required for neutrophil-EC and neutrophil-platelet interactions under inflammatory conditions (Li et al. JCI 2014; Kim et al. Blood 2015). In particular, we utilize blood of patients with sickle cell disease (SCD), an inherited blood disorder, and a mouse model of SCD (Berkeley) for our research because acute vaso-occlusion, a hallmark of SCD disease, is mediated by heterotypic cell-cell adhesion and aggregation. Our recent studies demonstrated that combination therapy of hydroxyurea (the only FDA-approved drug for treatment of SCD) and specific AKT inhibitors has immediate benefits on acute vaso-occlusion and survival in SCD mice (Barazia et al. Blood 2015; Kim et al. Haematologica 2017). We are currently investigating how AKT-NOXs signaling cooperatively and distinctly regulates heterotypic cell-cell interactions under thromboinflammatory conditions including vascular inflammation and ischemia/reperfusion injury.


3.    Role of transcription regulators in platelet activation and thrombosis.


Growing evidence shows that anucleate platelets contain many transcriptional regulators which are transferred from megakaryocytes during pro-platelet formation. However, it remains unclear which transcriptional regulators are present in platelets and what their roles are. We recently found that the mRNA and protein of Downstream Regulatory Element Antagonist Modulator (DREAM), a transcriptional repressor, are present in human and mouse platelets and that deletion of platelet DREAM significantly impairs the activity of phosphoinositide-3-kinase during platelet activation and thrombus formation (Kim et al. Blood 2017). Our work has identified DREAM as a novel target for anti-thrombotic agents.

Selected Publications

Kim K, Tseng A, Barazia A, Italiano JE, Cho J. DREAM plays an important role during platelet activation and thrombogenesis. Blood. 129: 209-225, 2017.


Kim K, Li J, Barazia A, Tseng A, Youn SW, Abbadessa G, Yu Y, Schwartz B, Andrews RK, Gordeuk VR, Cho J. ARQ 092, an orally-available, selective AKT inhibitor, attenuates neutrophil-platelet interactions in sickle cell disease.Haematologica. In Press.


Barazia A, Li K, Kim K, Shabrani N, Cho J. Hydroxyurea with AKT2 inhibition decreases vaso-occlusive events in sickle cell disease mice. Blood. 126: 2511-2517, 2015. (cover image)


Kim K, Li J, Tseng A, Andrews RK, Cho J. NOX2 is critical for heterotypic neutrophil-platelet interactions during vascular inflammation. Blood. 126: 1952-64, 2015.


Feng Q, Shabrani N, Thon JN, Huo H, Thiel A, Machlus KR, Kim K, Brooks J, Li F, Luo C, Kimbrel EA, Wang J, Kim KS, Italiano J, Cho J, Lu SJ, Lanza R. Scalable generation of universal platelets from human induced pluripotent stem cells.Stem Cell Reports. 3:817-31, 2014.


Wang Z, Li J, Cho J, Malik AB. Prevention of vascular inflammation by nanoparticle targeting of adherent neutrophils. Nat Nanotechnol. 9:204-10, 2014.


Li J, Kim K, Hahm E, Molokie R, Hay N, Gordeuk VR, Du X, Cho J. Neutrophil Akt2 regulates heterotypic cell-cell interactions during vascular inflammation. J Clin Invest. 124:1483-96, 2014. (Commentary in J Clin Invest. 124:1462-65, 2014).


Kim K, Hahm E, Li J, Holbrook LM, Sasikumar P, Stanley RG, Ushio-Fukai M, Gibbins JM, Cho J. Platelet protein disulfide isomerase is required for thrombus formation but not for hemostasis in mice. Blood. 122:1052-61, 2013.


Hahm E, Li J, Kim K, Huh S, Rogelj S, Cho J. Extracellular protein disulfide isomerase regulates ligand binding activity of αMβ2 inegrin and neutrophil recruitment during vascular inflammation. Blood. 121:3789-800, 2013. (Plenary Paper) (Commentary in Blood. 121:3779-80, 2013).


Lu SJ, Li F, Yin H, Feng Q, Kimbrel E, Hahm E, Thon J, Wang W, Italiano JE Jr, Cho J, Lanza R. Platelets generated from human embryonic stem cells are functional in vitro and in the microcirculation of living mice. Cell Res. 21: 530-45, 2011. (Co-corresponding author)