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Michael S. Sinensky, Ph.D.

Professor Emeritus on half-time appointment
Contact Information:
 J. H. Quillen College of Medicine, ETSU
Department of Biochemistry and Mol. Biol.
Box 70581, Johnson City TN 37614

Phone:  Lab-(423) 439-2026
            Office-(423) 439-8013
FAX: (423) 439-2030
email: sinensky@mail.etsu.edu 
Room B030 Building 178, VA Campus
Education
  • 1966 B.A., Chemistry, Columbia College, New York, New York
  • 1972 Ph.D., Biochemistry and Molecular Biology, Harvard University, Cambridge, Massachusetts

Interdisciplinary Association

Adjunct Professor of Internal Medicine, Quillen College of Medicine, ETSU Cardiovascular Research Institute


Research Interests

Genetic and metabolic regulation of biosynthetic enzymes in mammalian cells utilizing isoprenoid biosynthesis as a model system.

 The structure-function relationships of membrane lipids, the mechanism of regulation of membrane lipid composition and the role of structural parameters of cell membrane lipids in regulation of their biosynthesis.

 The role of mevalonate metabolism in mammalian cell-cycle progression.  Structure and function of prenylated proteins.  Of particular current interest is the role of prenylation dependent processing of the nuclear lamina proteins in regulation of cell growth and metabolism.

Our laboratory is currently working primarily on the functional significance of posttranslational modifications of proteins with isoprenoids, particularly with regard to the nuclear lamin proteins and p21ras. We are also interested in the regulation of cholesterol metabolism in mammalian cells and its relationship to atherogenesis.

The role of apoptotic induction in vascular cells in the development of atherosclerosis

The signal transduction pathway of oxysterol induced apoptosis. 

References

Dechat T, Shimi T, Adam SA, Rusinol AE, Andres DA, Spielmann HP, Sinensky MS, Goldman RD. Related Articles
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
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
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]
Freeman NE, Rusinol AE, Linton M, Hachey DL, Fazio S, Sinensky MS, Thewke D. Related Articles
Acyl-coenzyme A:cholesterol acyltransferase promotes oxidized LDL/oxysterol-induced apoptosis in macrophages.
J Lipid Res. 2005 Sep;46(9):1933-43. Epub 2005 Jul 1.
PMID: 15995174 [PubMed - indexed for MEDLINE]
Liu J, Thewke DP, Su YR, Linton MF, Fazio S, Sinensky MS. Related Articles
Reduced macrophage apoptosis is associated with accelerated atherosclerosis in low-density lipoprotein receptor-null mice.
Arterioscler Thromb Vasc Biol. 2005 Jan;25(1):174-9. Epub 2004 Oct 21.
PMID: 15499039 [PubMed - indexed for MEDLINE]
Corrigan DP, Kuszczak D, Rusinol AE, Thewke DP, Hrycyna CA, Michaelis S, Sinensky MS. Related Articles
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]
Sinensky M. Related Articles
Lipids and me.
Biochem Biophys Res Commun. 2002 Apr 19;292(5):1279-81. No abstract available.
PMID: 11969228 [PubMed - indexed for MEDLINE]
Panini SR, Yang L, Rusinol AE, Sinensky MS, Bonventre JV, Leslie CC. Related Articles
Arachidonate metabolism and the signaling pathway of induction of apoptosis by oxidized LDL/oxysterol.
J Lipid Res. 2001 Oct;42(10):1678-86.
PMID: 11590225 [PubMed - indexed for MEDLINE]
Panini SR, Sinensky MS. Related Articles
Mechanisms of oxysterol-induced apoptosis.
Curr Opin Lipidol. 2001 Oct;12(5):529-33. Review.
PMID: 11561172 [PubMed - indexed for MEDLINE]
Kloog Y, Cox AD, Sinensky M. Related Articles
Concepts in Ras-directed therapy.
Expert Opin Investig Drugs. 1999 Dec;8(12):2121-2140.
PMID: 11139843 [PubMed - as supplied by publisher]
Sinensky M. Related Articles
Functional aspects of polyisoprenoid protein substituents: roles in protein-protein interaction and trafficking.
Biochim Biophys Acta. 2000 Dec 15;1529(1-3):203-9. Review.
PMID: 11111089 [PubMed - indexed for MEDLINE]
Yang L, Sinensky MS. Related Articles
25-Hydroxycholesterol activates a cytochrome c release-mediated caspase cascade.
Biochem Biophys Res Commun. 2000 Nov 30;278(3):557-63.
PMID: 11095949 [PubMed - indexed for MEDLINE]
Thewke D, Kramer M, Sinensky MS. Related Articles
Transcriptional homeostatic control of membrane lipid composition.
Biochem Biophys Res Commun. 2000 Jun 24;273(1):1-4. Review.
PMID: 10873553 [PubMed - indexed for MEDLINE]
Sinensky M. Related Articles
Recent advances in the study of prenylated proteins.
Biochim Biophys Acta. 2000 Apr 12;1484(2-3):93-106. Review.
PMID: 10760460 [PubMed - indexed for MEDLINE]
Rusinol AE, Yang L, Thewke D, Panini SR, Kramer MF, Sinensky MS. Related Articles
Isolation of a somatic cell mutant resistant to the induction of apoptosis by oxidized low density lipoprotein.
J Biol Chem. 2000 Mar 10;275(10):7296-303.
PMID: 10702300 [PubMed - indexed for MEDLINE]
Kilic F, Johnson DA, Sinensky M. Related Articles
Subcellular localization and partial purification of prelamin A endoprotease: an enzyme which catalyzes the conversion of farnesylated prelamin A to mature lamin A.
FEBS Lett. 1999 Apr 30;450(1-2):61-5.
PMID: 10350058 [PubMed - indexed for MEDLINE]
Thewke DP, Panini SR, Sinensky M. Related Articles
Oleate potentiates oxysterol inhibition of transcription from sterol regulatory element-1-regulated promoters and maturation of sterol regulatory element-binding proteins.
J Biol Chem. 1998 Aug 14;273(33):21402-7.
PMID: 9694903 [PubMed - indexed for MEDLINE]
Siddiqui AA, Garland JR, Dalton MB, Sinensky M. Related Articles
Evidence for a high affinity, saturable, prenylation-dependent p21Ha-ras binding site in plasma membranes.
J Biol Chem. 1998 Feb 6;273(6):3712-7.
PMID: 9452502 [PubMed - indexed for MEDLINE]
Kilic F, Salas-Marco J, Garland J, Sinensky M. Related Articles
Regulation of prelamin A endoprotease activity by prelamin A.
FEBS Lett. 1997 Sep 1;414(1):65-8.
PMID: 9305733 [PubMed - indexed for MEDLINE]
Kilic F, Dalton MB, Burrell SK, Mayer JP, Patterson SD, Sinensky M. Related Articles
In vitro assay and characterization of the farnesylation-dependent prelamin A endoprotease.
J Biol Chem. 1997 Feb 21;272(8):5298-304.
PMID: 9030603 [PubMed - indexed for MEDLINE]
Dalton MB, Fantle KS, Bechtold HA, DeMaio L, Evans RM, Krystosek A, Sinensky M. Related Articles
The farnesyl protein transferase inhibitor BZA-5B blocks farnesylation of nuclear lamins and p21ras but does not affect their function or localization.
Cancer Res. 1995 Aug 1;55(15):3295-304.
PMID: 7614464 [PubMed - indexed for MEDLINE]