Joel D. Morrisett, Ph.D.
Professor of Medicine and Biochemistry/Molecular Biology
Basic and Clinical Research Interests:
The current standard of care for carotid atherosclerosis involves statin therapy. Statins not only inhibit cholesterol biosynthesis, but exert favorable pleiotropic effects on the arterial wall. Previous studies suggest that this drug can cause early regression of carotid atherosclerotic plaques. One of the objectives of our research program is to elucidate the mechanism(s) by which these favorable conditions occur. This objective is being pursued through three different approaches. The first approach is to determine in candidates for sequential carotid endarterectomy (CEA) if short term statin therapy alters the composition or dimensions of the plaque as measured in vivo and ex vivo by high resolution 3T MRI and feature space analysis. A second approach is to determine in candidates for bilateral CEA if short term therapy causes changes in tissue expression of mRNA that encodes proteins that modulate inflammation, oxidation, lipid transport, calcification, proteolysis, or hemorrhage. Laser capture microdissection, oligonucleotide microarray analysis, and high throughpout in situ hybridization (GenePaint), and immunohistochemistry (ProteinPaint) are being used to examine CEA tissues that have and have not been exposed to statin treatment. A third approach is to determine in candidates for bilateral CEA if short term statin therapy produces changes in CEA tissue and/or plasma levels of proteins involved in processes leading to atherosclerosis. This approach is being pursued using mass spectral imaging and high sensitivity protein microarray analysis (PMA). Mapping specific genes and proteins onto the 2D surface of histologic cross sections of atherosclerotic arteries provides useful information about the distribution of these macromolecules and how they might interact in vivo. These pharmacogenomic and pharmacoproteomic approaches have great potential for addressing central mechanisms leading to atherosclerosis and for discriminating between tissues that have/ have not been exposed to the pleiotropic effects of statins and other interventions.
- Choudhary S, Higgins CL, Chen IY, Reardon M, Lawrie G, Vick GW 3rd, Karmonik C, Via DP, Morrisett JD. Quantitation and localization of matrix metalloproteinases and their inhibitors in human carotid endarterectomy tissues. Arterioscler Thromb Vasc Biol 2006;26:2351-2358.
- Peterson LE, Hoogeveen RC, Pownall HJ, Morrisett JD . Classification Analysis of Surface Enhanced Laser Desorption/ Ionization Mass Spectral Serum Profiles for Prostate Cancer. Proceedings of the 2006 IEEE International Joint Congress on Neural Networks (IJCNN 2006), pp 3828-3835.
- Ohira T, Schreiner PJ, Morrisett JD, Chambless LE, Rosamond WD, Folsom AR. Lipoprotein(a) and incident ischemic stroke: the Atherosclerosis Risk in Communities (ARIC) study. Stroke 2006;37:1407-1412.
- Higgins CL, Marvel SA, Morrisett JD. Quantification of calcification in atherosclerotic lesions. Arterioscler Thromb Vasc Biol 2005;25:1567-1576.
- Ramaswamy A, Lin E, Chen I, Mitra R, Morrisett J, Coombes K, Ju Z, Kapoor M. Application of protein lysate microarrays to molecular marker verification and quantification. Proteome Sci 2005;3:9.
- Adams GJ, Baltazar U, Karmonik C, Bordelon C, Lin PH, Bush RL, Lumsden AB, Morrisett JD. Comparison of 15 different stents in superficial femoral arteries by high resolution MRI ex vivo and in vivo. J Magn Reson Imaging 2005;22:125-135.
- Adams GJ, Greene J, Vick GW 3rd, Harrist R, Kimball KT, Karmonik C, Ballantyne CM, Insull W Jr, Morrisett JD. Tracking regression and progression of atherosclerosis in human carotid arteries using high-resolution magnetic resonance imaging. Magn Reson Imaging 2004;22:1249-1258.
- J.D. Morrisett, W. Vick, R. Sharma, G. Lawrie, H. Safi, E. Ezell, J. Schwartz, G. Hunter, D. Gorenstein. Discrimination of Components in Atherosclerotic Plaques of Human Carotid Endarterectomy Specimens by Magnetic Resonance Imaging Ex Vivo., Mag Reson Imag 2003;21:465-474.
- Adams GJ, Vick GW, Bordelon CB, Insull W, and Morrisett JD. An Algorithm for Quantifying Advanced Carotid Artery Atherosclerosis in Humans using MRI and Active Contours. Proc SPIE Med Imaging 2002, pp 1448-1458.
- Adams GJ, Simoni DM, Bordelon CB Jr, Vick GW 3rd, Kimball KT, Insull W Jr, Morrisett JD. Bilateral symmetry of human carotid artery atherosclerosis. Stroke 2002;33:2575-2580.