Mehran M Sadeghi MD

Associate Professor of Medicine (Cardiology)

Research Interests

Molecular imaging; Nuclear imaging; Vascular biology; Molecular biology; Vascular remodeling; Atherosclerosis; Aneurysm; Transplantation; Valvular biology and imaging

Current Projects

  • Molecular Imaging of Vascular Remodeling
  • Molecular Imaging of Plaque Vulnerability
  • VEGF and Neuropilin-like Proteins in Vascular Remodeling

Research Summary

Molecular imaging provides a unique opportunity to link vascular and molecular biology and imaging, ultimately leading to the development of novel imaging approaches, both for research and clinical diagnostics. The ultimate goal of research in my laboratory is to develop novel imaging approaches to detect the molecular pathobiology of the vessel wall in vivo. Our comprehensive approach includes several components. Through basic vascular biology research we identify relevant molecular processes and potential targets for imaging (and therapeutics). Next, we use the state of the art technology to develop novel tracers targeted at relevant molecular markers, and establish molecular vascular imaging protocols in animal models of human disease. Finally, we exploit these techniques to further advance vascular biology and clinical research. We have made significant progress towards achieving these goals in the past few years. Specifically, we have focused on vascular remodeling, as the prototypic pathological vascular process shared by many vascular diseases, including atherosclerosis, graft arteriosclerosis, post-angioplasty restenosis, and aneurysm formation.

Extensive Research Description

Despite remarkable recent progress in molecular and vascular biology research, little has been achieved in adapting traditional imaging modalities to detect molecular pathobiology in vivo. Molecular imaging provides a unique opportunity to link vascular and molecular biology and imaging, ultimately leading to the development of novel imaging approaches, both for research and clinical diagnostics. The ultimate goal of research in my laboratory is to develop novel imaging approaches to detect the molecular pathobiology of the vessel wall in vivo. Our comprehensive approach includes several components. Through basic vascular biology research we identify relevant molecular processes and potential targets for imaging (and therapeutics). Next, we use the state of the art technology to develop novel tracers targeted at relevant molecular markers, and establish molecular vascular imaging protocols in animal models of human disease. Finally, we exploit these techniques to further advance vascular biology and clinical research. We have made significant progress towards achieving these goals in the past few years. Specifically, we have focused on vascular remodeling, as the prototypic pathological vascular process shared by many vascular diseases, including atherosclerosis, graft arteriosclerosis, post-angioplasty restenosis, and aneurysm formation. Our federally funded studies of the pathophysiology of vascular remodeling in graft arteriosclerosis, performed under the umbrella of the Interdepartmental Program in Vascular Biology and Transplantation at Yale have led to the identification novel molecular markers, including a neuropilin-like protein, ESDN, as a potential target for diagnosis and therapy of vascular remodeling. We have demonstrated that ESDN is upregulated in vascular remodeling, and have defined its function as regulator of vascular cell proliferation in vivo. We are currently in the process of defining other aspects of ESDN function, including its role in growth factor and integrin signaling pathways, and identification of ESDN ligands. In molecular imaging arena, we have identified and validated avß3 integrin activation as a target for imaging the proliferative process in vascular remodeling, and have demonstrated the suitability of a?ß3-targeted tracers for imaging graft arteriosclerosis. Matrix metalloproteinase (MMP) activation, as a key regulator of vascular remodeling, was targeted for in vivo imaging of injury-induced vascular remodeling and aneurysm formation using high resolution microSPECT imaging in conjunction with CT angiography for anatomical localization. We are currently in the process of optimizing the technical aspects of in vivo microSPECT/CT imaging to improve visualization and quantitation of molecular targets. In parallel, we have developed a novel “tracer design” concept for in vivo applications and have been involved in the development of a novel intravascular detection system which combines scintigraphy with high resolution optical coherence tomography imaging.


Selected Publications

  • Nie L, Guo X, Esmailzadeh L, Zhang J, Asadi A, Collinge M, Kim DJ, Jin SW, Dubrac A, Eichmann A, Simons M, Bender JR, Sadeghi MM. “Transmembrane protein ESDN promotes endothelial VEGF signaling and regulates angiogenesis”. Journal of Clinical investigation, 2013, in press
  • Zhang J, Razavian M, Tavakoli S, Nie L, Tellides G, Backer JM, Backer MV, Bender JR, Sadeghi MM. “Molecular imaging of VEGF receptors in graft arteriosclerosis”, Arterioscler Thromb Vasc Biol. 2012, 32:1489-55.
  • Razavian M, Marfatia R, Mongue-Din H, Tavakoli S, Sinusas AJ, Zhang J, Nie L, Sadeghi MM., Integrin-Targeted Imaging of Inflammation in Vascular Remodeling., ATVB 2011, 31:2820-6
  • Razavian M, Tavakoli S, Zhang J, Nie L, Dobrucki LW, Sinusas AJ, Azure M, Robinson S, Sadeghi MM. Atherosclerosis Plaque Heterogeneity and Response to Therapy Detected by in vivo Molecular Imaging of Matrix Metalloproteinase Activation. Journal of Nuclear Medicine, 2011, 52:1795-802
  • Tavakoli S, Razavian M, Zhang J, Nie L, Marfatia R, Dobrucki DS, Sinusas AJ, Edwards DS, Robinson S, Sadeghi MM. Monitoring the Progression of Vascular Remodeling and Response to Dietary Modification by Molecular Imaging of Matrix Metalloproteinase Activation, Atherosclerosis, Thrombosis and Vascular Biology, 2011, 31:102-109.
  • Zhang J, Silva T, Yarovinsky T, Manes TD, Tavakoli S, Nie L, Tellides G, Pober JS, Bender JR, Sadeghi MM. VEGF blockade inhibits lymphocyte recruitment and ameliorates immune-mediated vascular remodeling. Circulation Research. 2010 Aug 6;107(3):408-17. Epub 2010 Jun 10.
  • Razavian M, Zhang J, Nie L, Tavakoli S, Razavian N, Dobrucki LW, Sinusas AJ, Edwards DS, Azure M, Sadeghi MM. Molecular imaging of matrix metalloproteinase activation to predict murine aneurysm expansion in vivo. Journal of Nuclear Medicine. 2010 Jul;51(7):1107-15. Epub 2010 Jun 16.
  • Sadeghi MM, Glover DK, Lanza GM, Fayad ZA, Johnson LL. Imaging atherosclerosis and vulnerable plaque. J Nucl Med. 2010 May 1;51 Suppl 1:51S-65S. Epub 2010 Apr 15.
  • Guo X, Nie L, Esmailzadeh L, Zhang J, Bender JR, Sadeghi MM. Endothelial and Smooth Muscle-Derived Neuropilin-Like Protein (ESDN) Modulates Platelet-Derived Growth Factor (PDGF) Signaling in Human Vascular Smooth Muscle Cells Journal of Biological Chemistry, 2009 Oct 23;284(43):29376-82.
  • Tavakoli S, Sadeghi MM, Imaging of Vascular Biology in the Heart Current Cardiovascular Imaging Reports, 2009, 2:40-49.

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