Dr. Douglas Thewke

Douglas P. Thewke, Ph.D.

Associate Professor 


Thewke

Contact Information:
Mailing Address:
J. H. Quillen College of Medicine, ETSU
Department of Biomedical Sciences.
Box 70582, Johnson City TN 37614
Office: Room A107, Building 178, VA Campus
Phone:  Lab-(423) 439-8009
              Office-(423) 439-2131
FAX: (423) 439-2030
email:  

   

Education
1987-1993: Ph.D., Biochemistry University of Tennessee Department of Biochemistry Knoxville, TN 37996-0840

1983-1987: B.S., Biology Peru State College Peru, NE 68421-0010


Research Interests


Current Research Interest: Our current research focuses on understanding the pathophysiological role of oxidized LDL/oxysterol-induced apoptosis in atherosclerosis.  Atherosclerosis is a chronic inflammatory disease of the vascular wall during which macrophages in the vascular intima ingest atherogenic lipoproteins, such as modified low density lipoproteins (LDL), and transform into cholesteryl ester-laden foam cells.  Apoptotic foam cells have been well documented within atherosclerotic lesions. Our prior work showed that macrophage apoptosis represses lesion formation in mice, indicating that, at least in early lesions, macrophage apoptosis is anti-atherogenic.  In advanced lesions, there is strong evidence that apoptosis of macrophage-derived foam cells is a pro-atherogenic factor contributing to plaque instability and rupture.  Thus, the mechanisms regulating macrophage apoptosis are significant to both the development of lesions and the progression towards events that may directly trigger the acute clinical manifestations of atherosclerosis. Currently we are examining the role of cannabinoid receptors in regulating macrophage apoptosis and in the development of atherosclerosis in hyperlipidemic mice.   We are also investigating in the pharmacological manipulation of cannabinoid receptors as potential therapy for pancreatic cancer.

 

References

1.

Cannabinoid receptor type 2 (CB2) deficiency alters atherosclerotic lesion formation in hyperlipidemic Ldlr-null mice.

 

Netherland CD, Pickle TG, Bales A, Thewke DP.

 

Atherosclerosis. 2010 Nov;213(1):102-8. Epub 2010 Aug 19.

 

PMID: 20846652 [PubMed - indexed for MEDLINE]

 

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2.

Rimonabant is a dual inhibitor of acyl CoA:cholesterol acyltransferases 1 and 2.

 

Netherland C, Thewke DP.

 

Biochem Biophys Res Commun. 2010 Aug 6;398(4):671-6. Epub 2010 Jul 6.

 

PMID: 20609360 [PubMed - indexed for MEDLINE] Free PMC Article

 

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3.

Stimulation of Akt poly-ubiquitination and proteasomal degradation in P388D1 cells by 7-ketocholesterol and 25-hydroxycholesterol.

 

Liu J, Netherland C, Pickle T, Sinensky MS, Thewke DP.

 

Arch Biochem Biophys. 2009 Jul 1;487(1):54-8. Epub 2009 May 21.

 

PMID: 19464253 [PubMed - indexed for MEDLINE] Free PMC Article

 

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4.

AM-251 and SR144528 are acyl CoA:cholesterol acyltransferase inhibitors.

 

Thewke D, Freeman-Anderson N, Pickle T, Netherland C, Chilton C.

 

Biochem Biophys Res Commun. 2009 Apr 3;381(2):181-6. Epub 2009 Feb 11.

 

PMID: 19338772 [PubMed - indexed for MEDLINE] Free PMC Article

 

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5.

Cannabinoid (CB2) receptor deficiency reduces the susceptibility of macrophages to oxidized LDL/oxysterol-induced apoptosis.

 

Freeman-Anderson NE, Pickle TG, Netherland CD, Bales A, Buckley NE, Thewke DP.

 

J Lipid Res. 2008 Nov;49(11):2338-46. Epub 2008 Jul 9.

 

PMID: 18614816 [PubMed - indexed for MEDLINE] Free PMC Article

 

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6.

KGF induces lipogenic genes through a PI3K and JNK/SREBP-1 pathway in H292 cells.

 

Chang Y, Wang J, Lu X, Thewke DP, Mason RJ.

 

J Lipid Res. 2005 Dec;46(12):2624-35. Epub 2005 Sep 14.

 

PMID: 16162944 [PubMed - indexed for MEDLINE] Free Article

 

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7.

Acyl-coenzyme A:cholesterol acyltransferase promotes oxidized LDL/oxysterol-induced apoptosis in macrophages.

 

Freeman NE, Rusinol AE, Linton M, Hachey DL, Fazio S, Sinensky MS, Thewke D.

 

J Lipid Res. 2005 Sep;46(9):1933-43. Epub 2005 Jul 1.

 

PMID: 15995174 [PubMed - indexed for MEDLINE] Free PMC Article

 

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8.

Reduced macrophage apoptosis is associated with accelerated atherosclerosis in low-density lipoprotein receptor-null mice.

 

Liu J, Thewke DP, Su YR, Linton MF, Fazio S, Sinensky MS.

 

Arterioscler Thromb Vasc Biol. 2005 Jan;25(1):174-9. Epub 2004 Oct 21.

 

PMID: 15499039 [PubMed - indexed for MEDLINE] Free PMC Article

 

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9.

Prelamin A endoproteolytic processing in vitro by recombinant Zmpste24.

 

Corrigan DP, Kuszczak D, Rusinol AE, Thewke DP, Hrycyna CA, Michaelis S, Sinensky MS.

 

Biochem J. 2005 Apr 1;387(Pt 1):129-38.

 

PMID: 15479156 [PubMed - indexed for MEDLINE] Free PMC Article

 

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10.

AKT/protein kinase B regulation of BCL family members during oxysterol-induced apoptosis.

 

Rusiñol AE, Thewke D, Liu J, Freeman N, Panini SR, Sinensky MS.

 

J Biol Chem. 2004 Jan 9;279(2):1392-9. Epub 2003 Oct 14.

 

PMID: 14559920 [PubMed - indexed for MEDLINE] Free Article

 

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11.

Transcriptional homeostatic control of membrane lipid composition.

 

Thewke D, Kramer M, Sinensky MS.

 

Biochem Biophys Res Commun. 2000 Jun 24;273(1):1-4. Review.

 

PMID: 10873553 [PubMed - indexed for MEDLINE]

 

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12.

Isolation of a somatic cell mutant resistant to the induction of apoptosis by oxidized low density lipoprotein.

 

Rusiñol AE, Yang L, Thewke D, Panini SR, Kramer MF, Sinensky MS.

 

J Biol Chem. 2000 Mar 10;275(10):7296-303.

 

PMID: 10702300 [PubMed - indexed for MEDLINE] Free Article

 

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13.

The expression of mRNAs for hepatocyte growth factor/scatter factor, its receptor c-met, and one of its activators tissue-type plasminogen activator show a systematic relationship in the developing and adult cerebral cortex and hippocampus.

 

Thewke DP, Seeds NW.

 

Brain Res. 1999 Mar 13;821(2):356-67.

 

PMID: 10064822 [PubMed - indexed for MEDLINE]

 

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14.

Oleate potentiates oxysterol inhibition of transcription from sterol regulatory element-1-regulated promoters and maturation of sterol regulatory element-binding proteins.

 

Thewke DP, Panini SR, Sinensky M.

 

J Biol Chem. 1998 Aug 14;273(33):21402-7.

 

PMID: 9694903 [PubMed - indexed for MEDLINE] Free Article

 

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15.

Expression of hepatocyte growth factor/scatter factor, its receptor, c-met, and tissue-type plasminogen activator during development of the murine olfactory system.

 

Thewke DP, Seeds NW.

 

J Neurosci. 1996 Nov 1;16(21):6933-44.

 

PMID: 8824331 [PubMed - indexed for MEDLINE] Free Article

 

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16.

Functional recognition of the neuronal tyrosine hydroxylase cAMP regulatory element in different cell types.

 

Huang ZM, Thewke D, Gong QQ, Schlichter D, Wicks WD.

 

Brain Res Mol Brain Res. 1991 Oct;11(3-4):309-19.

 

PMID: 1684632 [PubMed - indexed for MEDLINE]

 

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