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Dr. Fadi Khasawneh's Lab

Research Goals

The Khasawneh lab focuses on two areas:

  1. The role of the regulators of G-protein signaling in platelet activation
  2. The mechanistic impact of thirdhand smoke on platelet function and thrombotic disease.

The biology of the regulators of G-protein signaling: While much is known about extrinsic regulators of platelet function, considerably much less is known regarding the intrinsic intracellular mechanisms modulating platelet activation following vascular injury. To this end, the regulators of G protein signaling (RGS proteins) are known to interact with and negatively regulate G-proteins, mainly by acting as GTPase activating proteins [GAPs] in many cell types. While much is known about their function in other cell systems, they remain poorly studied in platelets at homeostasis or under pathophysiological conditions. Our lab focuses on investigating the regulation and function of RGS proteins in platelets. Indeed, we have shown that RGS10, 16 and 18 play key regulatory roles in platelet activation and thrombus formation, mainly through acting as a braking system.

Thirdhand smoke impact on thrombogenesis: Even though there have been worldwide efforts to combat tobacco use, it is still a highly significant health problem for both smokers and nonsmokers. While it’s easier to appreciate its negative effects on smokers, the same cannot be said for the public health effects resulting from (indirect) exposure to tobacco smoke. Relatively recently, a new and rather tenacious threat has been discovered. This threat, now referred to as Third-Hand Smoke (THS), is formed from toxicants produced by Second-Hand Smoke that end up depositing on surfaces such as upholstery, curtains, car seats, carpet, etc. These toxicants can over time undergo chemical reactions and changes (aging) that may make them more toxic. Our lab aims to understand the mechanistic impact of exposure to THS, including that which takes place in utero, in the context of occlusive disorders. We have documented that THS does in fact increase the risk of thrombotic disease states, and that it does so by triggering a hyperactive platelet state.

Lab Funding

  • R01HL145053-01A1 Khasawneh (PI); The Impact of Third-Hand Smoke on Platelet Function and Thrombogenesis, NHLBI; 2019 – 2024
  • R21ES029345-01A1 Khasawneh (PI); In Utero Third-Hand Smoke Impact on Platelet Function and Thrombogenesis, NIEHS; 2018 – 2022/NCE
  • 18AIREA33960421 Alshbool (PI), Khasawneh (Co-I); Investigation of the Platelet 5HT2A and P2Y1 Receptors, AHA; 2018 – 2021/NCE           
  • 1R03 ES030486-A1 Alshbool (PI), Khasawneh (Co-I); The Impact of Third-Hand E‐Cigarette Exposure on Platelet Function and Thrombogenesis, NIEHS; 2020 - 2022. 

Recent Publications

  • Karim Z.A., Hensch N.R., Qasim H., Alshbool F.Z., and Khasawneh F.T.*, “Role of IkB Kinase b in Regulating the Remodeling of the CARMA1-Bcl10-MALT1 Complex”, Biochem Biophys Res Commun, 500 (2018) 268-274
  • Alshbool F.Z., Karim Z.A., Espinosa E.V.P., Lin O.A., and Khasawneh F.T.*, “Investigation of a Thromboxane A2 Receptor-Based Vaccine For Managing Thrombogenesis”, J Am Heart Assoc. 2018 Jun 23;7(13). pii: e009139.
  • Qasim H., Karim Z.A., Silva-Espinoza J.C., Khasawneh F.T., Rivera J.O., Ellis C.C., Bauer S.L., Almeida I.C., and Alshbool F.Z., “Short-term E-cigarette Exposure Increases the Risk of Thrombogenesis and Enhances Platelet Function in Mice”, J Am Heart Assoc. 2018;7:e009264. DOI: 10.1161/JAHA.118.009264
  • Zhu Y., Romero E.L., Ren X., Du C., Liu C., Karim Z.A., Alshbool F.Z., Khasawneh F.T., Zhou J., Zhong D., and Geng B., “Enabling H2S Biomedicine: Clopidogrel as a Clinical Donor Probe and Thioenol Derivatives as Flexible Promoieties”, Nat Commun. 2018 Sep 27;9(1):3952
  • Hernandez, K.R., Karim Z.A., Qasim H., Druey K.M., Alshbool F.Z., and Khasawneh F.T.*, “The Regulator of G-Protein Signaling 16 is a Negative Modulator of Platelet Function and Thrombosis”, J Am Heart Assoc. 2019 Mar 5;8(5):e011273.
  • Qasim H., Karim Z.A., Hernandez, K.R., Lozano, D., Khasawneh F.T., and Alshbool F.Z., “Arhgef1 Plays a Vital Role in Platelet Function and Thrombogenesis”, J Am Heart Assoc. 2019 May 7;8(9):e011712.
  • Espinosa E.V.P., Lin O.A., Karim Z.A., Alshbool F.Z., and Khasawneh F.T.*, “Mouse Transient Receptor Potential Channel Type 6 Selectively Regulates Agonist-Induced Platelet Function”, Biochem Biophys Rep. 2019 Aug 31;20:100685
  • Hassanzadah M., Bitar A.H., Khanfar N.M., Khasawneh F.T., Lutfy K., and Shankar G.S., “A Retrospective Cohort Study of the Prevalence of Anxiety and Agitation in Schizophrenic Smokers and the Unmet Needs of Smoking Cessation Programs”, Medicine. 2019 Oct;98(40):e17375
  • Alarabi A.B., Karim Z.A., Ramirez, J.E.M., Hernandez, K.R., Lozano, P.A., Rivera J.O., Alshbool F.Z., and Khasawneh F.T.*, ”Short-Term Exposure to Waterpipe Smoke Triggers a Hyperactive Platelet Activation State and Increases the Risk of Thrombogenesis”, Arterioscler Thromb Vasc Biol. 2020 Feb;40(2):335-349
  • Ortiz-Munoz G, Yu MA, Lefrançais E, Mallavia B, Valet C, Tian JJ, Ranucci S, Wang KM, Liu Z, Kwaan N, Dawson D, Kleinhenz ME, Khasawneh F.T., Haggie PM, Verkman AS, Looney MR., “Cystic fibrosis transmembrane conductance regulator dysfunction in platelets drives lung hyperinflammation.” J Clin Invest. 2020 Apr 1;130(4):2041-2053
  • Ramirez J.E.M., Karim Z.A., Alarabi A.B., Hernandez K.R., Taleb Z.B., Rivera R.O., Khasawneh F.T., and Alshbool F.Z., “The JUUL E-Cigarette Elevates the Risk of Thrombosis and Potentiates Platelet Activation”, J Cardiovasc Pharmacol Ther. 2020 Jul 21:107424842094168.
  • Alarabi A.B., Karim Z.A., Hinojos V., Lozano P.A., Hernandez K.R., Ramirez J.E.M., Ali H.E.A., Khasawneh F.T., Alshbool FZ.,” The G-protein βγ subunits regulate platelet function”, Life Sci. 2020 Sep 22;262:118481
  • Malhotra A., Reddy I. K., Fulford M., Khasawneh, F.T., Tiwari A. K., and Feng X. “Strategies for the Integration of Foundational and Clinical Sciences in Doctor of Pharmacy Programs”, J Am Coll Clin Pharm. 2021; DOI: 10.1002/jac5.1482.

Lab Members

medhat elhalawany dr.-hamdy-ali daniel villalobos

Dr. Medhat El-Halawany
Research Scientist          

Dr. Hamdy Ali
Postdoctoral Research Associate

Dr. Daniel Villalobos
Postdoctoral Research Associate

rodrigues leticia dante delancy carlie clipson

Ms. Leticia Rodrigues
Research Assistant

Mr. Danree Delancy
Student Research Assistant

Ms. Carlie Clipson
Student Research Assistant