Scientific Report 2003-2004 - Cleveland Clinic Lerner Research ...

The Department of Cancer BiologyContinued from Page 46protein. Thus, constitutive activation of Stat3contributes to the pathogenesis of glioblastomaby promoting both proliferation and survival ofGBM cells. Therefore, targeting Stat3 signalingmay provide a potential therapeutic interventionfor GBM (Oncogene 2002;21:8404-13).Dr. Taolin Yi’s group has been investigatingthe role of the tyrosine phosphatase SHP-1in signal transduction and leukemiogenesis. Anexciting new development is the discovery of asmall molecule inhibitor of this phosphatase,sodium stibogluconate, which in preclinicalstudies (in collaboration with Dr. Ernest Borden,Taussig Cancer Center, Drug Discovery andDevelopment) is showing promise as anantitumor agent, either alone or in combinationwith other therapeutics (J. Immunol.2002;169:5978-85). The Yi laboratory has alsoidentified the prolactin (PRL) family ofoncogenic phosphatases as targets for developinganticancer therapeutics. They have shown thatpentamidine, an anti-protozoa drug with anunknown mechanism of action, is an inhibitor ofPRLs, both in cell cultures and of humanmelanoma tumors grown in nude mice. Theseobservations suggest the potential of pentamidinein anticancer therapies and may provide abasis for developing novel protein tyrosinephosphatase-targeted therapeutics (Mol. CancerTher. 2002;1:1255-64).In recent years, lysophospholipids havebeen recognized as important cell signalingmolecules. The laboratory of Dr. Yan Xu hasbeen at the forefront of these advances. Hergroup has identified the cell surface receptor forthe cell membrane and serum lipidlysophosphatidylcholine (LPC) as G2A, alymphocyte-expressed G-protein-coupledreceptor whose genetic ablation results in thedevelopment of autoimmunity. Ovarian cancerG-protein-coupled receptor 1 (OGR1, orGPR68), and G-protein-coupled receptor 4(GPR4) have also been identified as receptors forsphingosylphosphorylcholine and LPC (BiochimBiophys Acta 2002;1582:81-8).Dr. Michael Vogelbaum is interested inmechanisms of apoptosis induction in glioblastoma.He is also collaborating with Drs.Silverman and Haque to identify novel strategiesfor therapeutic intervention in this brain tumortype.Protein kinase C regulation is the subjectof research in two laboratories. Dr. FirouzDaneshgari, a urologist with a research interest inthe regulation of protein kinase C signaling in theurothelium, is working with Dr. Thomas Powell,who is investigating the role of protein kinase Cisoforms in the induction of apoptosis.Dr. Jawhar Rawwas is a pediatric hematologistand oncologist who is interested in themechanisms of resistance to retinoic acid in thechildhood cancer neuroblastoma, including therole of cellular retinoic acid binding proteins andtheir possible interactions with N-myc. Dr.Rawwas is a member of the NeuroblastomaBiology Subcommittee of the Children’s OncologyGroup.The newest member of the Cancer Biologydepartment is Dr. Nywana Sizemore, who hasbeen recruited to the Section of ColorectalCancer Research headed by Dr. Casey. Herresearch interests encompass the role of aberrantsignal transduction by AKT and IKK in controllinggene expression, oncogenesis, and apoptosis incolorectal cancer. Dr. Sizemore discovered a rolefor the phosphatidylinositol 3' kinase (PI3K)/AKT cell survival pathway in the positiveregulation of NFκB. She also showed that thetumor suppressor PTEN negatively regulatesNFκB activity. She has also found that IKKregulates the activation of α-catenin, a criticalfactor regulating colorectal epithelial celltranscription.The Department of Cancer Biology has anactive training program at the graduate studentand postdoctoral levels. Several staff membershave joint appointments at Case Western ReserveUniversity, Cleveland State University and KentState University. Presently, 13 graduate studentsare completing their thesis research in thedepartment, and several rotation and summerstudents spend time throughout the year invarious department laboratories. Three studentsgraduated with a Ph.D. degree during the pastyear. Postdoctoral training is an importantactivity in the department, and we presently haveover 51 fellows representing an internationalcadre of trainees. The training program includes aseminar series, journal club, and meetings with theTaussig Cancer Center Translational Therapeuticsgroup. Trainees are also encouraged to attendother relevant weekly sessions at the LRI seminarsand the annual LRI retreat. Funds are availableto enable trainees to attend national and internationalmeetings to present their work, and thedepartment has an excellent record in obtainingcompetitive travel awards to relevant conferences.47