skip to main content
Give

Dr. Fatima Alshbool's Lab

Research Goals

The Alshbool lab focuses on two areas:

  1. The impact of e-cigarettes on platelet function and thrombogenesis.
  2. Investigating structural biology of platelet G-protein coupled receptors.  

The impact of e-cigarette exposure on platelet biology.
Cardiovascular disease remains the number one killer, not only in the United States but also worldwide. Smoking has been found to be a major contributor to cardiovascular disease, and to be a major cause of morbidity and mortality. Additionally, platelets are known to play a major role in smoking-induced cardiovascular disease. To this end, e-cigarettes represent a relatively new form of smoking, and have been gaining popularity around the U.S., especially among the youth, pregnant women, and other vulnerable populations. The increase in their usage is primarily due to the perception that they are a safer alternative to cigarette smoking. Nonetheless, recent evidence demonstrated that e-cigarettes are not harm free or emission free devices, and that they do cause negative health effects on multiple systems, including the cardiovascular. However, whether e-cigarettes modulate platelet function, and increase the risk of thrombosis remains ill defined. Our goal is to determine the impact of e-cigarettes on platelet function and thrombus formation. We documented for the first time, using a novel model of whole body e-cigarette short term exposure that e-cigarettes enhance platelet function, modulate hemostasis and increase the risk of thrombogenesis.

Structural biology of platelet G protein coupled receptors (GPCRs).
While there is considerable interest in identifying agents that target platelet GPCRs, and many have been made thus far, the majority has failed thus far. To this end, we believe this is due to lack of information regarding their ligand-binding pocket and structural biology. To address these issues, we designed and characterized several function blocking antibodies that were designed against the ligand binding regions of platelet GPCRs. We observed that an antibody for the P2Y1 receptor and more recently the P2Y12 receptor block platelet activation and protect against thrombus formation. Additionally, we are characterizing the function-blocking activity of antibody raised against the ligand binding domain of the 5HT2A receptor. Information gathered via our studies can be used for designing small molecule inhibitors of these receptors, and/or these antibodies can themselves be purposed as therapeutic agents.

 

Lab Funding

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

Recent Publications

  • Alarabi AB, Karim ZA, Hinojos V, Lozano PA, Hernandez KR, Montes Ramirez JE, Ali HEA, Khasawneh FT, Alshbool FZ.,” The G-protein βγ subunits regulate platelet function”, Life Sci. 2020 Sep 22;262:118481.
  • Ben Taleb Z, Kalan ME, Bahelah R, Boateng GO, Rahman M, Alshbool FZ.,” Vaping while high: Factors associated with vaping marijuana among youth in the United States”, Drug Alcohol Depend. 2020 Sep 15;217:108290.
  • 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., 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
  • 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
  • Qasim H., Alarabi A.B., Alzoubi K.H., Karim Z.A., Alshbool F.Z.*, and Khasawneh F.T. ”The effects of hookah/waterpipe smoking on general health and the cardiovascular system”, Environ Health Prev Med. 2019 Sep 14;24(1):58.
  • 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. doi: 10.1161/JAHA.118.011712.
  • 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.
  • 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
  • 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
  • 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. doi: 10.1161/JAHA.118.009139.
  • Hensch N.R., Karim Z.A., Pineda J., Mercado N., Alshbool F.Z., Khasawneh F.T., “P2Y12 Antibody Inhibits Platelet Activity and Protects Against Thrombogenesis”, Biochem Biophys Res Commun, 493 (2017) 1069-1074.
  • Qasim H, Karim ZA, Rivera JO, Khasawneh FT, Alshbool FZ*. “The Impact of Electronic Cigarettes on the Cardiovascular System”, J Am Heart Assoc. 2017 Aug 30;6(9). pii: e006353. doi: 10.1161/JAHA.117.006353
  • Alshbool F.Z., Karim Z.A., Vemana H., Conlon C., Khasawneh F.T., “The Regulator Of G-Protein Signaling 18 Regulates Platelet Aggregation, Hemostasis And Thrombosis”, Biochem Biophys Res Commun. 2015 Jul; 462(4):378-82.
  • Karim Z.A., Alshbool F.Z., Vemana H., Adhami N., Dhall S., Espinosa E.V.P., Martins-Green M., and Khasawneh F.T., “Third Hand Smoke: Impact on Hemostasis and Thrombogenesis”, J Cardiovasc J Cardiovasc Pharmacol. 2015 Aug; 66(2):177-82.
  • Karim Z.A., Vemana H., Alshbool F.Z., Lin O.A., Alshehri A.M., Javaherizadeh P., Espinosa E.V.P., and Khasawneh F.T., “Characterization of a Novel Function-Blocking Antibody Targeted Against The Platelet P2Y1 Receptor”, Arterioscler Thromb Vasc Biol. 2015 Mar; 35(3):637-44.

Lab Members

ahmed alarabi

Dr. Ahmed Alarabi
Postdoctoral Research Associate