University of South Florida

Deborah Kuhn

The 2004 graduate, Dr. Deborah Kuhn, is now a postdoctoral fellow with Dr. Robert Z. Orlowski at M.D. Anderson Cancer Center in Texas.  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 will receive funding 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.

Book Chapter:

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.

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Yu Pan

The program’s second graduate (May 2005), Dr. Yu Pan, joined the laboratory of Dr. W. Stratford May, then director of the Shands Cancer Center, Gainesville, Florida. She is currently a dental student in Minnesota.

Dr. Pan’s publication record while in the Program:

Chen L, Gilkes DM, Pan Y, Lane WS, Chen J.  ATM and Chk2-dependent phosphorylation of MDMX contribute to p53 activation after DNA damage.  EMBO J.  2005 Oct 5;24(19):3411-22.  Epub 2005 Sep 15.

Pan Y, Chen J.  Modification of MDMX by sumoylation.  Biochem Biophys Res Commun. 2005 Jul 8;3323(3):702-9.

Chen L, Li C, Pan Y, Chen J.  Regulation of p53-MDMX interaction by casein kinase 1 alpha.  Mol Cell Biol.  2005 Aug;25(15):6509-20.

Pan Y, Chen J.  MDM2 promotes ubiquitination and degradation of MDMX.  Mol Cell Bio.  2003 Aug;23(15):5113-21.

Publications since graduation:

Gilkes DM, Pan Y, Coppola D, Yeatman T, Reuther GW, Chen J. Regulation of MDMX expression by mitogenic signaling. Mol Cell Biol. 2008 Mar;28(6):1999-2010. Epub 2008 Jan 2.

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Cynthia LeBron

Cancer Biology's third graduate (May 2007), Dr. Cynthia LeBron received offers from Georgetown, Yale and Johns Hopkins. She has chosen the laboratory of Dr. David Sidransky at Johns Hopkins University for her postdoctoral fellowship.

Dr. LeBron's publication record while in the Program:

Eason DD, LeBron C, Coppola D, Moscinski LC, Livingston S, Sutton ET, Blanck G.  Development of CD30+ lymphoproliferative disease in mice lacking interferon regulatory factor-1.  Oncogene.  2003 Sep 18;22(40):6166-76.

LeBron C, Chen L, Gilkes D, Chen J.  Regulation of MDMX nuclear import and degradation by Chk2 and 14-3-3.  EMBO Journal . 25: 1196-1206. (2006)

Dr. LeBron's publication record since graduation:

Kim MS, Lebron C, Nagpal JK, Chae YK, Chang X, Huang Y, Chuang T, Yamashita K, Trink B, Ratovitski EA, Califano JA, Sidransky D.Methylation of the DFNA5 increases risk of lymph node metastasis in human breast cancer.Biochem Biophys Res Commun. 2008 May 23;370(1):38-43. Epub 2008 Mar 17.

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Jose Rodriguez

Graduating in August, 2007, Dr. Jose Rodriguez, returned to his home country of Puerto Rico and entered the Ponce School of Medicine to pursue his M.D. degree,

Dr. Rodriguez's publication record while in the Program:

Rodriguez JM , Michele A. Glozak MA, Ma Y, Cress WD. Bok, Bcl-2 related ovarian killer, is cell cycle regulated and sensitizes to stress induced apoptosis. Journal of Biological Chemistry.  2006 Aug 11; 281(32):22729-35.

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Scott Freeman

Dr. Scott Freeman, shown with his Major Professor, Dr. Doug Cress, successfully defended his dissertation defense on October 15, 2007. Dr. Freeman is currently a postdoctoral fellow in the lab of Dr. Gerald Bepler, division chief of Thoracic Oncology at the Moffitt Cancer Center. Dr. Bepler is also director of the Moffitt Comprehensive Lung Cancer Research Center.

Dr. Freeman's publication record while in the Program:

Ma Y, Freeman SN, Cress WD.  E2F4 Deficiency Promotes Drug-Induced Apoptosis.  Cancer Biol Ther.  2004 Dec 14;3(12):1262-9.

Freeman SN, Bepler G, Haura E, Sutphen R, Cress WD.  Re: Prognostic significance of short sequence insertion in the MCL-1 promoter in chronic lymphocytic leukemia. J Natl Cancer Inst. 2005 Jul 20;97(14):1088-9.

Freeman SN, Ma Y, Cress WD.RhoBTB2 (DBC2) is a mitotic E2F1 target gene with a novel role in apoptosis.J Biol Chem. 2008 Jan 25;283(4):2353-62. Epub 2007 Nov 26.

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Joseph A. Wahle

Dr. Joe Wahle, pictured at his reception with Cancer Biology Program Director Ken Wright, defended his dissertation on October 19, 2007. Dr. Wahle has joined the lab of Dr. Wayne Yokoyama, Washington University, St. Louis.

Dr. Wahle's publication record while in the Program:

Wahle JA, Paraiso KHT, Costello AL, Goll EL, Sentman CL, Kerr WG. Cutting Edge:  Dominance by an MHC-Independent Inhibitory Receptor Compromises NK Killing of Complex Targets. J Immunol.  2006 Jun 15;176(12):7165-9

Wahle JA, Paraiso KH, Kendig RD, Lawrence HR, Chen L, Wu J, Kerr WG .Inappropriate recruitment and activity by the Src homology region 2 domain-containing phosphatase 1 (SHP1) is responsible for receptor dominance in the SHIP-deficient NK cell.J Immunol. 2007 Dec 15;179(12):8009-15.

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Ildefonso Vicente-Suarez

Dr. Ildefonso Vicente-Suarez, pictured with one of his committee members, Dr. Julie Djeu, successfully defended his disseration on October 24, 2007. Dr. Vicente-Suarez has joined the lab of Dr. Hilde Cheroutre, La Jolla Institute of Allergy and Immunology, UCSD.

Dr. Vicente-Suarez's publication record while in the Program:

Vicente-Suarez I, Takahashi Y, Cheng F, Horna P, Wang HW, Wang HG, Sotomayor EM.Identification of a novel negative role of flagellin in regulating IL-10 production.Eur J Immunol. 2007 Nov;37(11):3164-75.

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Daniele Gilkes

Dr. Daniele Gilkes, the first USF Presidential Fellow in the Cancer Biology Program, is pictured with her Major Professor, Dr. Jiandong Chen following her successful dissertation defense on February 25, 2008. Dr. Gilkes has joined Dr. Chen's lab as a postdoctoral fellow.

Dr. Gilkes' publication record while in the Cancer Biology Program:

Nefedova Y, Cheng P, Gilkes DM, Blaskovich M, Beg AA, Sebti SM, Gabrilovich DI. Activation of dendritic cells via inhibition of Jak2/STAT3 signaling. J Immunol 2005 Oct 1;175(7):4338-46.

Chen L, Gilkes DM, Pan Y, Lane WS, Chen J. ATM and Chk2-dependent phosphorylation of MDMX contribute to p53 activation after DNA damage. EMBO J. 2005 Oct 5;24(19):3411-22. Epub 2005 Sep 15.

Hu B, Gilkes DM, Farooqi B, Sebti S, Chen J. MDMX overexpression prevents P53 activation by the MDM2 inhibitor nutlin. J Biol Chem. 2006 Aug 11; [Epub ahead of print].

LeBron C, Chen L, Gilkes D, Chen J. Regulation of MDMX nuclear import and degradation by Chk2 and 14-3-3. EMBO Journal . 2006 Mar 22;25(6):1196-206. Epub 2006 Mar 2.

Gilkes, DM, Chen, L., and Chen, J. (2006). MDMX regulation of p53 response to ribosomal stress. Embo J 25, 5614-5625.

Hu, B., Gilkes, DM, Farooqi, B., Sebti, S. M., and Chen, J. (2006). MDMX overexpression prevents p53 activation by the MDM2 inhibitor Nutlin. J Biol Chem 281, 33030-33035.

Hu B, Gilkes DM, Chen J. (2007) Efficient p53 activation and apoptosis by simultaneous disruption of binding to MDM2 and MDMX. Cancer Res. Sep 15;67(18):8810-7.

Gilkes DM, and Chen, J. (2007). Distinct roles of MDMX in the regulation of p53 response to ribosomal stress. Cell Cycle 6, 151-155.

Gilkes DM, Pan Y, Coppola D, Yeatman T, Reuther GW, Chen J. Regulation of MDMX expression by mitogenic signaling. Mol Cell Biol. 2008 Mar;28(6):1999-2010. Epub 2008 Jan 2.

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Adam Carie

Dr. Adam Carie (second from right), shown with his committee following his dissertation defense. Pictured from left to right: Dissertation Chair Adrienne Cox, UNC-Chapel Hill, Committee members Hong-Gang Wang, Noreen Luetteke and Srikumar Chellappan; Adam and Major Professor Said Sebti. Dr. Carie is now a Senior Scientist, Pre-Clinical Development, Intezyne Techonologies.

Adam has the distinction of being the first graduate from the Program to be named as a Commencement speaker.

Dr. Carie's publication record while in the Program:

Sun J, Wang DA, Jain RK, Carie A, Paquette S, Ennis E, Blaskovich MA, Baldini L, Coppola D, Hamilton AD, Sebti SM. Inhibiting angiogenesis and tumorigenesis by synthetic molecule that blocks binding of both VEGF and PDGF to their receptors. Oncogene. 2005 Jul 7;24(29):4701-9.

Zhou H, Wang D, Baldini L, Ennis E, Jain R, Carie A, Sebti S, Hamilton A. Structure-activity studies on a library of potent calyx[4]arene-based antagonists that inhibit PDGF-stimulated PDGFR tyrosine phosphorylation. Org Biomol Chem. 2006 Jun 21;4(12):2376-86. Epub 2006 May 10.

Carie A, Sebti S. A Chemical Biology Approach Identifies a Beta 2 Andrenergic Receptor Agonist that Causes Human Tumor Regression by Blocking the Raf-1/Mek/Erk1/2 Pathway. Oncogene. 2007 May 31;26(26):3777-88. Epub 2007 Jan 29.

Kinkade R, Dasgupta P, Carie A, Pernazza D, Carless M, Pillai S, Lawrence N, Sebti S, Chellappan S. A small molecule disruptor of Rb-Raf-1 interaction inhibits cell proliferation, angiogenesis and growth of human tumor xenografts in nude mice. Cancer Res. 2008 May 15;68(10):3810-8.

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Dr. Rebecca "Becky" Kinkade Davis is shown with her committee following her defense on March 31, 2008. Pictured from right to left: Committee members Eric Haura, Said Sebti; Major Professor Srikumar Chellappan; Becky; Committee member Doug Cress and Dissertation Chair Scott Hiebert from University of Vanderbilt School of Medicine. Dr. Kinkade is a postdoctoral fellow in the lab of Dr. Alan Fields, Mayo Clinic, Jacksonville.

The USF Graduate School selected Dr. Davis's dissertation to receive the Outstanding Dissertation Award for academic year 2008-2009. This pretigous award is given to only two doctoral students each year; Dr. Davis will be honored with a plaque and monetary award in Fall 2009.

Dr. Kinkade's publication record while in the Program:

Gardner, R.A.; Kinkade, R.; Wang, C; Phanstiel, O., IV. (2004) Total Synthesis of Petrobactin and its Homologues as Potential Growth Stimuli for Marinobacterhydrocarbonoclasticus, an Oil-Degrading Bacteria. J. Org. Chem.; 69 (10); 3530-3537

Dasgupta P, Kinkade R, Joshi B, DeCook C, Haura E, Chellappan S. Nicotine inhibits apoptosis induced by chemotherapeutic drugs by up-regulating XIAP and surviving. Proc Natl Acad Sci U S A. 2006 Apr 18;103(16):6332-7. Epub 2006 Apr 6.

Kinkade, R., Dasgupta, P. Chellappan, S. The ABCs of Targeting Raf: Novel Approaches to Cancer Therapy. Curr Cancer Ther Rev, 2: 305-314, 2006.

Kinkade, R., Rizwani, W. and Chellappan, S. (2007) E2F transcription factors in cell proliferation, apoptosis, senescence and cancer. In `Control of cellular physiology by transcription factors E2F’. Dr. Kenichi Yoshida, Editor. Research Signpost Press.

Kinkade R, Dasgupta P, Carie A, Pernazza D, Carless M, Pillai S, Lawrence N, Sebti S, Chellappan S. A small molecule disruptor of Rb-Raf-1 interaction inhibits cell proliferation, angiogenesis and growth of human tumor xenografts in nude mice. Cancer Res. 2008 May 15;68(10):3810-8.

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Nicholas "Nick" Woods

Dr. Nicholas Woods, shown with his wife and fellow Cancer Biology student Neha Kabra, successfully defended his dissertation on August 25, 2008. Nick has joined the lab of Dr. Julie Djeu at the Moffitt Cancer Center as a postdoctoral fellow. Nick and Neha are awaiting the birth of their son, Nikhil, in October.

Dr. Woods' publication record while in the Program:

Yamaguchi H, Woods NT, Dorsey JF, Takahashi Y, Gjertsen NR, Yeatman T, Wu J, Wang HG. SRC directly phosphorylates BIF-1 and prevents its interaction with Bax and the initiation of anoikis. J Biol Chem. 2008 May 12. [Epub ahead of print]

Woods NT, Yamaguchi H, Lee FY, Bhalla KN, Wang HG.Anoikis, initiated by Mcl-1 degradation and Bim induction, is deregulated during oncogenesis. Cancer Res. 2007 Nov 15;67(22):10744-52.

Ren Y, Chen Z, Chen L, Woods NT, Reuther GW, Cheng JQ, Wang HG, Wu J.Shp2E76K mutant confers cytokine-independent survival of TF-1 myeloid cells by up-regulating Bcl-XL. J Biol Chem. 2007 Dec 14;282(50) :36463-73. Epub 2007 Oct 17.

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