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:

1.   Cellular and molecular mechanisms regulating atherosclerosis. 
2.   Cannabinoid receptor signaling in disease.
3.   Cell signaling

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. 

Research Support:

Current Support
:

R15HL113878-01A1 “Modulations of atherosclerosis by cannabinoid type 2 receptor”; National Heart, Lung, and Blood Institute; Douglas P Thewke, P.I.; Antonio Rusinol, Co-Investigator; Stacy Brown, Co-Investigator; project period 01/10/2013 to 12/31/2015 

Prior Support:

R15 HL085137 “The Role of CB2 Receptors in oxLDL-Induced Apoptosis and Atherogenesis” National Heart, Lung, and Blood Institute; Douglas P Thewke, P.I.; project period 8/01/06-7/31/09 

R01 DK58071 “Regulation of stearoyl-CoA desaturases by oleate” National Institute of Diabetes and Digestive and Kidney Diseases; Douglas P Thewke, P.I.; project period 8/01/01-7/31/05 

Scientist Development Grant American Heart Association “Regulation of Transcription by Oleate” Douglas P Thewke, P.I.; project period 8/1/99-7/31/00

Lab Members:

Makenzie Fulmer-graduate student
Emilee Englehaupt-undergraduate student, Honors College
Zachary Lahrs-undergradate student
Mathew Holt- undergraduate student
Thomas Christian-undergraduate student
Ben Cearlock-medical student
Kaitlyn Hinshaw-medical student
Brett Farmer-medical student
Chase Mussard-undergradate student, Honors College

Publications:

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]

 

Related citations

 

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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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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