Antonio E. Rusiñol, Ph.D.

Assistant Professor 

Research Interests

My research is focused on two major areas:

A) Elucidation the molecular pathways and mechanisms of the early events of atherogenesis:  The cytotoxic effects of oxLDL have been shown to proceed through apoptotic pathways. Work reported by our group (see bellow), and others, is consistent with the hypothesis that the induction of apoptosis by oxLDL is mediated by oxysterols. A long term goal of our laboratory is to determine whether macrophage foam cell apoptosis, induced by oxysterols, plays a significant role in atherogenesis.

B) Role of protein prenylation on traffic, function and disease: Protein prenylation can be considered as a mechanism for post-translational attachment of proteins to membranes and targeting signal for intracellular localization . All known prenylated proteins in the cell are found at least under certain conditions, bound to cellular membranes. However, although prenylation clearly mediates membrane association, other factors must determine the specificity of the subcellular localization of particular prenylated proteins since they occur in many diverse subcellular compartments. In some cases this specificity is given by secondary signals in the prenylated proteins (primary structure or additional lipid modifications) whereas in other cases it is the actual interaction with prenylation-specific receptors or protein partners that directs the final localization. The existence of such prenylation-specific binding proteins has been demonstrated by work from our laboratory (1) and work published by others. The function of such proteins is however, not clearly understood. The overall goal of our research is to determine the role of prenylation-specific binding proteins on H-ras and Prelamin A trafficking and function.

References

Singh SK, Suresh MV, Prayther DC, Moorman JP, Rusiñol AE, Agrawal A.   Phosphoethanolamine-complexed C-reactive protein: A pharmacological-like macromolecule that binds to native low-density lipoprotein in human serum. Clin Chim Acta. 2008 Aug;394(1-2):94-8. Epub 2008 Apr 27. PMID: 18486609 [PubMed - in process] Singh SK, Suresh MV, Prayther DC, Moorman JP, Rusiñol AE, Agrawal A. C-reactive protein-bound enzymatically modified low-density lipoprotein does not transform macrophages into foam cells. J Immunol. 2008 Mar 15;180(6):4316-22. PMID: 18322245 [PubMed - indexed for MEDLINE]   Liu Y, Wang Y, Rusinol AE, Sinensky MS, Liu J, Shell SM, Zou Y. Related Articles, Involvement of xeroderma pigmentosum group A (XPA) in progeria arising from defective maturation of prelamin A. FASEB J. 2007 Sep 11; [Epub ahead of print] PMID: 17848622 [PubMed - as supplied by publisher] Dechat T, Shimi T, Adam SA, Rusinol AE, Andres DA, Spielmann HP, Sinensky MS, Goldman RD. Alterations in mitosis and cell cycle progression caused by a mutant lamin A known to accelerate human aging. Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):4955-60. Epub 2007 Mar 14. PMID: 17360326 [PubMed - in process] Liu Y, Rusinol A, Sinensky M, Wang Y, Zou Y. Related Articles, Links DNA damage responses in progeroid syndromes arise from defective maturation of prelamin A. J Cell Sci. 2006 Nov 15;119(Pt 22):4644-9. Epub 2006 Oct 24. PMID: 17062639 [PubMed - indexed for MEDLINE] Rusinol AE, Sinensky MS. Related Articles, Links Farnesylated lamins, progeroid syndromes and farnesyl transferase inhibitors. J Cell Sci. 2006 Aug 15;119(Pt 16):3265-72. Review. PMID: 16899817 [PubMed - indexed for MEDLINE] Steagall RJ, Rusinol AE, Truong QA, Han Z. Related Articles, Links HSPA12B is predominantly expressed in endothelial cells and required for angiogenesis. Arterioscler Thromb Vasc Biol. 2006 Sep;26(9):2012-8. Epub 2006 Jul 6. PMID: 16825593 [PubMed - indexed for MEDLINE

Freeman NE, Rusinol AE, Linton M, Hachey DL, Fazio S, Sinensky MS, Thewke DP.   Acyl-CoA: Cholesterol acyltransferase promotes oxidized LDL/oxysterol-induced apoptosis in macrophages. J Lipid Res. 2005 Jul 1; [Epub ahead of print]

Corrigan DP, Kuszczak D, Rusinol AE, Thewke DP, Hrycyna CA, Michaelis S, Sinensky MS.   Prelamin A endoproteolytic processing in vitro by recombinant Zmpste24. Biochem J. 2005 Apr 1;387(Pt 1):129-38. PMID: 15479156 [PubMed - indexed for MEDLINE]

Rusinol AE, Thewke D, Liu J, Freeman N, Panini SR, Sinensky MS.   Akt/PKB regulation of Bcl family members during oxysterol induced apoptosis. J Biol Chem. 2003 Oct 14 [Epub ahead of print] PMID: 14559920 [PubMed - as supplied by publisher]