Carolyn M. Klinge, Ph.D.

Education:Carolyn M. Klinge, Ph.D. 

B.A. magna cum laude, Biology, Keuka College, Keuka Park, NY; 1979
M.S. Genetics, M.S. Hershey College of Medicine, Pennsylvania State University; 1981
Ph.D. Pharmacology, M.S. Hershey College of Medicine, Pennsylvania State University; 1984
Postdoctoral fellowship, Department of Biochemistry, University of Rochester School of Medicine, 1984-89

Curriculum Vitae

Current Positions:

Professor of Biochemistry and Molecular Genetics, University of Louisville School of Medicine
University Scholar

Contact Information

Delia Baxter Building, Room 221E
570 South Preston Street
Louisville, KY 40202
Office: 502-852-3668
Labs: 502-852-1643 and 502-852-7594
Email: carolyn.klinge@louisville.edu

Department Website:

http://louisville.edu/medicine/departments/biochemistry/our_people/klinge

Research Description:

My research focuses on the molecular mechanisms accounting for acquired endocrine resistance in breast cancer.  I have expertise in cell-based studies on estrogen receptor (ER)-DNA interaction, transcriptional regulation of mRNA and miRNA, protein expression, baculovirus-production of recombinant estrogen receptors, membrane-initiated/nongenomic signaling by estrogens and endocrine disruptors, ChIP of ERα, ERβ, and COUP-TFII to gene promoters, RNA seq, use of MetaCore GO pathway analysis software, statistical evaluation for quantitative data analyses.  I teach graduate courses in the Graduate Program in Biochemistry and Molecular Genetics and am a member of the 3 person biochemistry/genetics teaching team for the integrated Molecular Basis of Life, Defense, and Disease first year M.D. curriculum.  I am PI of NIH T35 DK072923 Summer Endocrine Research Training program for second year M.D. students since its initial funding in 2006.

I am also PI on an NIH R21 grant CA219252 with Dr. Christine Schaner-Tooley at the University of Buffalo: “HNRNPA2B1 as a reader of RNA methylation in breast cancer.”   Current projects in the lab include examining the role of HNRNPA2B1 in regulating the miRNA transcriptome of breast cancer cells and, in an ongoing collaboration with Dr. David Schultz, Associate Professor of Biology, determining if anacardic acid will block the development of acquired endocrine resistance in breast cancer cells. 

Literature Cited:

COUP-TFII in breast cancer cells

  1. Klinge CM, Driscoll MD, Sathya G, Bambara RA, Hilf R.  Chicken Ovalbumin Upstream Promoter-Transcription Factor (COUP-TF) interacts with estrogen receptor and binds to estrogen response elements and a single half-site as a homodimer in vitro.  Journal of Biological Chemistry 1997 Dec 12;272(10):31465-74. (CMK corresponding author) PMID: 9395481.
  2. Riggs KA, Wickramasinghe NS, Cochrum RK, Watts MB, Klinge CM.  Decreased chicken ovalbumin upstream promoter transcription factor II expression in tamoxifen-resistant breast cancer cells.  Cancer Research 2006 Oct 15;66(20):10188-98.  PMID: 17047084.  [ http://cancerres.aacrjournals.org/content/66/20/10188.long ]
  3. Litchfield LM, Riggs KA, Hockenberry AM, Oliver LD, Barnhart KG, Fox JM, Cai J, Pierce WM Jr, Ivanova MM, Bates PJ, Datta S, Appana SN, Kulesza P, McBryan J, Young LS, Klinge CM.  Identification and characterization of nucleolin as a COUP-TFII co-activator of retinoic acid receptor beta transcription in breast cancer cells.  PLoS One 2012;7(5):e38278.  PMID:22693611.  PMCID: PMC3365040.
  4. Litchfield LM, Appana SN, Datta S, Klinge CM.  COUP-TFII inhibits NFκB activation in breast cancer cells and restores endocrine sensitivity.  Molecular & Cellular Endocrinology 2014 Jan 25;382(1):358-67.  Epub 2013 Oct 7. PMID:24141032.  PMCID: PMC3469769.  NIHMS408414.

Estrogen receptors and gender disparity in lung adenocarcinoma cells

  1. Dougherty SM, Mazhawidza W, Bohn AS, Robinson KA, Mattingly KA, Blankenship KA, Huff MO, McGregor WG, Klinge CM.  Gender difference in the activity but not expression of estrogen receptors alpha and beta in human lung adenocarcinoma cells.  Endocrine-Related Cancer 2006 Mar;13(1):113-34.  PMID: 16601283.  PMCID: PMC1472635.
  2. Ivanova MM, Mazhawidza W, Dougherty SM, Klinge CM.  Sex differences in estrogen receptor subcellular location and activity in lung adenocarcinoma cells.  American Journal of Respiratory Cell & Molecular Biology 2010 Mar;42(3):320-30.  Epub 2009 Jun 25.  PMID: 19556604.  PMCID: PMC2830404.
  3. Klinge CM, Radde BN, Imbert-Fernandez Y, Teng Y, Ivanova MM, Abner SM, Martin AL.  Targeting the intracellular MUC1 C-terminal domain inhibits proliferation and estrogen receptor transcriptional activity in lung adenocarcinoma cells.  Molecular Cancer Therapeutics 2011 Nov;10(11):2062-71. Epub 2011 Aug 23.  PMID: 21862684.  PMCID: PMC3213286.
  4. Teng Y, Litchfield LM, Ivanova MM, Prough RA, Clark BJ, Klinge CM.  Dehydroepiandrosterone-induces miR-21 through estrogen receptor beta and androgen receptor.  Molecular & Cellular Endocrinology 2014 Jul 5;392(1-2):23-36. Epub 7 May.  PMID: 24845419.  PMCID: PMC4074919.

Mitochondrial function in breast cancer cells

  1. Radde BN, Ivanova MM, Mai HX, Slabei JK, Hill BG, Klinge CM.  Bioenergetic differences between MCF-7 and T47D breast cancer cells and their regulation by estradiol and tamoxifen. Biochemical Journal 2015 Jan 1;465(1):49-61.  Epub Oct 3, 2014.  PMID: 25279503.
  2. Bonsignore LA, Sergesketter JB, Klinge CM, Schaner Tooley CE.  Loss of the N-terminal methyltransferase NRMT1 increases sensitivity to DNA damage and promotes mammary oncogenesis.  Oncotarget 2015 May 20;20(14):12248-63.  Epub Mar 26, 2015.  PMID: 25909287.  PMCID: PMC4494936.
  3. Radde BN, Alizehdia-Rad N, Price SM, Schultz DJ, Klinge CM.  Anacardic acid inhibits breast cancer cell proliferation by inhibiting mitochondrial bioenergetic function.  Journal of Cellular Biochemistry 2016;117:2521-32.  PMID:26990649.
  4. Radde BN, Ivanova MM, Mai HX, Alizehdia-Rad N, Piell K, Van Hoose P, Cole MP, Kulesza P, Hill BG, Klinge CM.  Nuclear respiratory factor-1 and bioenergetics in tamoxifen-resistant breast cancer cells.  Experimental Cell Research 2016 Sep 10;347(1):222-31.  PMID:27515002.

Mechanisms of endocrine-resistance

  1. Manavalan TT, Teng Y, Appana SN, Datta S, Kalbfleisch TS, Li Y, Klinge CM.  Differential expression of microRNA expression in tamoxifen-sensitive MCF-7 versus tamoxifen-resistant LY2 human breast cancer cells.  Cancer Letters 2011 Dec 26;313(1):26-43.  Epub 2011 Sep10.  PMID: 21955614.  PMCID: PMC3214732.  NIHMSID: NIHMS325067.
  2. Muluhngwi P, Krisha A, Vittitow SL, Napier JT, Richardson K, Ellis M, Mott JL, Klinge CM.  Tamoxifen differentially regulates miR-29b-1 and miR-29a expression depending on endocrine-sensitivity in breast cancer cells.  Cancer Letters 2017 Mar 1;388:230-38.  DOI: 10.1016/j.canlet.2016.12.007.  PMID: 27986463.  PMCID: PMC5318263.
  3. Muluhngwi P, Alizadeh-Rad N, Vittitow SL, Kalbfleisch TS, Klinge CM.  The miR-29 transcriptome in endocrine-sensitive and resistant breast cancer cells.  Scientific Reports 2017 Jul 12;7(1):5205.  DOI: 10.1038/s41598-017-05727-w.  PMID:28701793.  PMCID: PMC5507892.  
  4. Schultz DJ, Krishna A, Vittitow SL, Alizadeh-Rad N, Muluhngwi P, Rouchka EC, Klinge CM.  Transcriptomic response of breast cancer cells to anacardic acid.  Scientific Reports 2018 May 23;8(1):8063.  DOI: 10.1038/s41598-018-26429-x.  Epub 23 May 2018.  PMID: 29795261. PMCID: PMC5966448.

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