The 2004 graduate, Dr. Deborah Kuhn, is Director of Scientific Affairs, The Binding Site, Houston, Texas. During her time in academia, Dr. Kuhn received the K99/R00 Pathway to Independence grant from the NCI.
Dr. Kuhn was previously a postdoc in the lab of Dr. Robert Orlowski. Dr. Orlowski is the Director of the Department of Lymphoma and Myeloma and Associate Professor in the Department of Experimental Therapeutics. Deborah received a post-doctoral fellowship from the American Cancer Society for her project "Development of Immunoproteasome-specific Inhibitors as Anti-cancer Agents" from the American Cancer Society. She was funded for three years to pursue this project.
Dr. Kuhn’s publication record while in the Program:
Chen D, Daniel KG, Chen MS, Kuhn DJ, Landis-Piwowar KR, Dou QP. Dietary flavonoids as proteasome inhibitors and apoptosis inducers in human leukemia cells. Biochm Parmacol. 2005 May 15;69(10):1421-32.
Kuhn DJ, Dou QP. Direct inhibition of interleukin-2 receptor alpha-mediated signaling pathway induces G1 arrest and apoptosis in human head-and-neck cancer cells. J Cell Biochem. 2005 May 15;95(2):379-90.
Kuhn DJ, Dou QP. The role of interleukin-2 receptor alpha in cancer. Front Biosci. 2005 May1;10:1462-74.
Kuhn DJ, Wang Y, Minic V, Coates C, Reddy GS, Daniel KG, Shim JY, Chen D, Landis-Piwowar KR, Miller FR, Turos E, Dou QP. Structure-activity relationships OF N-methylthiolated beta-lactam antibiotics with C3 substitutions and their selective induction of apoptosis in human cancer cells. Front Biosci. 2005 May1;10:1183-90.
Landis-Piwowar KR, Kuhn DJ, Wan SB, Chen D, Chan TH, Dou QP.Evaluation of proteasome-inhibitory and apoptosis-inducing potencies of novel (-)-EGCG analogs and their prodrugs. Int J Mol Med. 2005 Apr;15(4):735-42.
Wan SB, Landis-Piwowar KR, Kuhn DJ, Chen D, Dou QP, Chan TH.Structure-activity study of epi-gallocatechin gallate (EGCG) analogs as proteasome inhibitors. Biorg Med Chem. 2005 Mar 15;13(6):2177-85.
Lam WH, Kazi A, Kuhn DJ, Chow LM, Chan AS, Dou QP, Chan TH. A potential prodrug for a green tea polyphenol proteasome inhibitor: evaluation of the peracetate ester of (-)-epigallocatechin gallate [(-)-EGCG]. Bioorg Med Chem. 2004 Nov 1;12(21):5587-93.
Chen D, Daniel KG, Kuhn DJ, Kazi A, Bhuiyan M, Li L, Wang Z, Wan SB, Lam WH, Chan TH, Dou QP. Green tea and tea polyphenols in cancer prevention. Front Biosci. 2004 Sep 1;9:2618-31.
Kuhn DJ, Burns AC, Kazi A, Dou QP. Direct inhibition of the ubiquitin-proteasome pathway by ester bond-containing green tea polyphenols is associated with increased expression of sterol regulatory element-binding protein 2 and LDL receptor. Biochim Biophys Acta. 2004 Jun 1;1682 (1-3):1-10.
Kazi A, Hill R, Long TE, Kuhn DJ, Turos E, Dou QP. Novel N-thiolated beta-lactam antibiotics selectively induce apoptosis in human tumor and transformed, but not normal or nontransformed, cells. Biochem Pharmacol. 2004 Jan 15;67(2):365-74.
Kazi A, Urbizu DA, Kuhn DJ, Acebo AL, Jackson ER, Greenfelder GP, Kumar NB, Dou QP. A natural musaceas plant extract inhibits proteasome activity and induces apoptosis selectively in human tumor and transformed but no normal and non-transformed, cells. Int J Mol Med. 2003 Dec; 12(6):879-87.
Kuhn DJ, Smith DM, Pross S, Whiteside TL, Dou QP. Overexpression of interleukin-2 receptor alpha in a human squamous cell carcinoma of the head and neck cell line is associated with increased proliferation, drug resistance, and transforming ability. J Cell Biochem. 2003 Jul 1;89(4):824-36.
Publications since graduation:
Kuhn DJ, Chen Q, Voorhees PM, Strader JS, Shenk KD, Sun CM, Demo SD, Bennett MK, van Leeuwen FW, Chanan-Khan AA, Orlowski RZ. Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma. Blood. 2007 Nov 1;110(9):3281-90. Epub 2007 Jun 25
Voorhees PM, Chen Q, Kuhn DJ, Small GW, Hunsucker SA, Strader JS, Corringham RE, Zaki MH, Nemeth JA, Orlowski RZ. Inhibition of interleukin-6 signaling with CNTO 328 enhances the activity of bortezomib in preclinical models of multiple myeloma. Clin Cancer Res. 2007 Nov 1;13(21):6469-78.
Chen Q, Xie W, Kuhn DJ, Voorhees PM, Lopez-Girona A, Mendy D, Corral LG, Krenitsky VP, Xu W, Moutouh-de Parseval L, Webb DR, Mercurio F, Nakayama KI, Nakayama K, Orlowski RZ. Targeting the p27 E3 ligase SCF(Skp2) results in p27- and Skp2-mediated cell-cycle arrest and activation of autophagy. Blood. 2008 May 1;111(9):4690-9. Epub 2008 Feb 27.
Orlowski RZ, Kuhn DJ. Proteasome inhibitors in cancer therapy: lessons from the first decade. Clin Cancer Res. 2008 Mar 15;14(6):1649-57.
Kuhn DJ, Hunsucker SA, Chen Q, Voorhees PM, Orlowski M, Orlowski RZ. Targeted inhibition of the immunoproteasome is a potent strategy against models of multiple myeloma that overcomes resistance to conventional drugs and non-specific proteasome inhibitors. Blood. 2008 Dec 2. [Epub ahead of print]
Shah JJ, Kuhn DJ, Orlowski RZ. Bortezomib and EGCG: no green tea for you? Blood. 2009 Jun 4;113(23):5695-6. doi: 10.1182/blood-2009-03-204776. No abstract available. PMID: 19498025
Voorhees PM, Chen Q, Small GW, Kuhn DJ, Hunsucker SA, Nemeth JA, Orlowski RZ.Targeted inhibition of interleukin-6 with CNTO 328 sensitizes pre-clinical models of multiple myeloma to dexamethasone-mediated cell death. Br J Haematol. 2009 Mar 6. Epub ahead of print.
Kuhn DJ, Orlowski RZ, Bjorklund CC. Second generation proteasome inhibitors: carfilzomib and immunoproteasome-specific inhibitors (IPSIs). Curr Cancer Drug Targets. 2011 Mar;11(3):285-95. Review. PMID: 21247387
Hunsucker SA, Magarotto V, Kuhn DJ, Kornblau SM, Wang M, Weber DM, Thomas SK, Shah JJ, Voorhees PM, Xie H, Cornfeld M, Nemeth JA, Orlowski RZ. Blockade of interleukin-6 signalling with siltuximab enhances melphalan cytotoxicity in preclinical models of multiple myeloma. Br J Haematol. 2011 Mar;152(5):579-92. doi: 10.1111/j.1365-2141.2010.08533.x. Epub 2011 Jan 17. PMID: 21241278
Bjorklund CC, Ma W, Wang ZQ, Davis RE, Kuhn DJ, Kornblau SM, Wang M, Shah JJ, Orlowski RZ. Evidence of a role for activation of Wnt/beta-catenin signaling in the resistance of plasma cells to lenalidomide. J Biol Chem. 2011 Apr 1;286(13):11009-20. doi: 10.1074/jbc.M110.180208. Epub 2010 Dec 28. PMID: 21189262
Kuhn DJ, Orlowski RZ. The immunoproteasome as a target in hematologic malignancies. Semin Hematol. 2012 Jul;49(3):258-62. doi: 10.1053/j.seminhematol.2012.04.003. Review. PMID: 22726549
Jones RJ, Bjorklund CC, Baladandayuthapani V, Kuhn DJ, Orlowski RZ. Drug resistance to inhibitors of the human double minute-2 E3 ligase is mediated by point mutations of p53, but can be overcome with the p53 targeting agent RITA. Mol Cancer Ther. 2012 Oct;11(10):2243-53. doi: 10.1158/1535-7163.MCT-12-0135. Epub 2012 Aug 28. PMID: 22933706
Kuhn DJ, Berkova Z, Jones RJ, Woessner R, Bjorklund CC, Ma W, Davis RE, Lin P, Wang H, Madden TL, Wei C, Baladandayuthapani V, Wang M, Thomas SK, Shah JJ, Weber DM, Orlowski RZ. Targeting the insulin-like growth factor-1 receptor to overcome bortezomib resistance in preclinical models of multiple myeloma. Blood. 2012 Oct 18;120(16):3260-70. doi: 10.1182/blood-2011-10-386789. Epub 2012 Aug 29. PMID: 22932796
Kuhn DJ, Zeger EL, and Orlowski RZ. (2006) Drugs: Proteasome Inhibitors and Modulators of Heat Shock Protein Function. In Update Cancer Therapeutics, Eds. R. Schilsky P.M. Sondel, G. Giaccone. Annual 23, In press. 2006.