Versiti - Roy L. Silverstein, MD | Versiti Blood Research Institute
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Roy L.

Silverstein, MD

Senior Investigator

Transfusion Medicine, Vascular Biology & Cell Therapy

Senior Investigator

Professor and Chairman Emeritus
Department of Medicine, Medical College of Wisconsin

Education and training

MD, Emory University School of Medicine, 1979
Residency in Internal Medicine, Hematology and Medical Oncology, New York Hospital Cornell Medical Center

Contact
Email RSilverstein@Versiti.org
Phone 414-955-0518
Links MyNCBI

Research Interests

Platelet and macrophage biology and atherothrombosis, with emphasis on molecular mechanisms through which the innate immune receptor CD36 mediates pro-thrombotic and pro-atherogenic signaling events in platelets and macrophages in the setting of chronic inflammation.  Recent focus has been on mitochondrial metabolic reprogramming and redox stress.

Lab Team

Mirza Ahmar Beg, PhD
Postdoctorall Fellow

Vaya Chen
Research Lab Technician

Grant Support

Ongoing Research Support

  • 1R01HL164460-01A1  Silverstein/Chen/Shapiro (MPI) 04/01/23-03/31/27. NKA/CD36 signaling in adipocytes promotes oxidative stress and drives chronic inflammation in atherosclerosis.
    Role: Communicating PI
  • 1R01HL153397-01A1 Silverstein/Cui (MPI) 04/01/2021-03/31/2025. Pim1 kinase coordinates PPAR gamma pathway and mitochondrial function to mediate pro- atherogenic responses in macrophages.
    Role: Communicating PI

Selected Publications

  1. Huang W, Li R, Zhang J, Chen Y, Ramakrishnan DP, Silverstein RL. A CD36 transmembrane domain peptide interrupts CD36 interactions with membrane partners on macrophages and inhibits atherogenic functions. Translational Research 2022; Nov 12; S1931-5244(22)00224-9. doi: 10.1016/j.trsl.2022.10.005.
  2. Yang M, Silverstein RL. Targeting Cysteine Oxidation in Thrombotic Disorders. Antioxidants. 2024 Jan 9:13(1):83. Doi: 10.3390/antiox13010083.
  3. Chen V, Zhang J, Chang J, Beg MA, Vick L, Wang Y, Wang D, Gupta A, Pereira D, Sodhi K, Shapiro JI, Silverstein RL, Malarkannan S, Chen Y. CD36 Restricts Lipid-Associated Macrophages Accumulation in White Adipose Tissues During Atherogenesis. Front Cardiovasc Med. 2024 (in press).
  4. Febbraio M, Podrez EA, Smith JD, Hazen SL, Hoff HF, Sharma K, Hajjar DP, and Silverstein RL. Targeted disruption of the Class B scavenger receptor, CD36, protects against atherosclerotic lesion development in mice. J. Clin. Invest. 2000. 105:1049-1056. PMCID: PMC300837.
  5. Jimenez B, Volpert OV, Crawford SE, Febbraio M, Silverstein RL and NP Bouck. Signals leading to apoptosis-dependent inhibition of neovascularization by thrombospondin-1. Nature Medicine 2000; 6:41-48.
  6. Rahaman SO, Lennon DJ, Febbraio M, Podrez EA, Hazen SL, Silverstein RL. CD36-dependent activation of c-Jun N-terminal kinase by oxidized LDL is required for macrophage foam cell formation. Cell Metabolism 2006;4(3):211-221. PMCID: PMC1855263.
  7. Park YM, Febbraio M, Silverstein RL. CD36 modulates macrophage migration in response to oxidized LDL: A mechanism of macrophage trapping. J. Clin. Invest. 2009; 119(1):136-145. PMCID: PMC2613464.
  8. Podrez EA, Byzova TV, Febbraio M, Salomon RG, Ma Y, Valiyaveettil M, Poliakov E, Sun M, Finton PJ, Curtis BR, Chen J, Zhang R, Silverstein RL, and SL Hazen. Platelet CD36 links hyperlipidemia, oxidant stress and a pro-thrombotic phenotype. Nature Medicine 2007; 13(9):1086-1095. PMCID: PMC3042888.
  9. Ghosh A, Li W, Febbraio M, Espinola RG, Cotrell E, McCrae K, and Silverstein RL. Platelet CD36 mediates interactions with endothelial cell-derived microparticles and contributes to thrombosis in vivo. J. Clin. Inv. 2008;118(5):1934-1943. PMCID: PMC2323190.
  10. Ren B, Hale J, Srikanthan S, Silverstein RL. Lysophosphatidic Acid Suppresses Endothelial Cell CD36 Expression and Promotes Angiogenesis via a PKD-1 Dependent Signaling Pathway. Blood 2011;117(22):6036-45. PMCID: PMC3112047
  11. Yang M, Cooley BC, Li W, Chen Y, Vasquez-Vivar J, Scoggins NO, Cameron S, Morrell CN, Silverstein RL. Platelet CD36 Promotes Thrombosis by Activating Redox Sensor ERK5 in Hyperlipidemic Conditions. Blood. 2017 May 25; 129(21):2917-2927. PMCID: PMC5445574.
  12. Chen Y, Huang W, Yang M, Xin G, Cui W, Xie Z, Silverstein RL. Cardiotonic Steroids Stimulate Macrophage Inflammatory Responses Through a Pathway Involving CD36, TLR4, and Na/K-ATPase. Arterioscler Thromb Vasc Biol. 2017; 37(8):1462-1469. PMCID: PMC5532064.
  13. Chen Y, Yang M, Huang W, Chen W, Zhao Y, Schulte ML, Volberding P, Gerbec Z, Zimmermann MT, Zeighami A, Demos W, Zhang J, Knaack D, Smith BC, Cui W, Malarkannan S, Sodhi K, Shapiro JI, Xie J, Sahoo D, Silverstein RL. Mitochondrial metabolic reprogramming by CD36 signaling drives macrophage inflammatory responses. Circ Res. 2019 Dec 6, 125:1087-1102. PMCID: PMC6921463.
  14. Dai W, Zhang H, Lund H, Zhang S, Castleberry M, Rodriguez M, Kuriakose G, Gupta S, Lewandowska M, Powers HR, Valmiki S, Zhu J, Shapiro AD, Hussain MM, López JA, Sorci-Thomas MG, Silverstein RL, Ginsberg HN, Sahoo D, Tabas I, Zheng Z. Intracellular tPA-PAI-1 interaction determines VLDL assembly in hepatocytes.  Science 2023; Sep;381(6661):eadh5207.