Claudio Research Summary

 

Pier Paolo Claudio, M.D., Ph.D.Pier Paolo Claudio, M.D., Ph.D.
Associate Professor
Department: Biochemistry and Microbiology
Research Cluster: Cancer Biology
Phone: (304) 696-3516
Fax: (304) 696-3713
E-mail: claudiop@marshall.edu
Office: BBSC 336-Q
Laboratory: BBSC 312









Research Summary

The focus of our laboratory is to understand the molecular mechanisms governing malignant transformation in order to tailor novel therapeutic strategies. To effectively design novel biological drugs, a further understanding of the mechanism of cancer pathogenesis is required. Toward this end, we have carried out in the past 15 years studies to understand the crosstalk between those factors that contribute to cancer progression versus those that protect from it.

The ultimate destiny of a cell results from an intricate balance between multiple regulators including oncogenes, tumor suppressor genes, cell cycle associated proteins, and growth factors. Deregulation of the cell cycle machinery switches the phenotype from a normal cell to a cancerous cell. Fundamental alteration of tumor suppressor genes may result in an unregulated cell cycle with the accumulation of mutations and eventual neoplastic transformation. As such, one may define cancer as a genetic disease of the cell cycle.

One of the most well-studied tumor suppressor genes is the retinoblastoma gene and its product pRb/p105. The recently identified protein, p130 along with p107 and pRb/p105 comprise the Retinoblastoma family of proteins. We have demonstrated the growth suppressive properties of p130 in lung cancer cell lines as well as in vivo in xenografts mouse model using viral delivery of the p130 gene, suggesting that p130 could be a novel biological drug. In a follow up of these in vivo studies we found that overexpression of the wild-type p130 gene interferes with the angiogenic process by specifically down-regulating VEGF.

Gene therapy offers great potential for combating and curing a wide range of pathologic lesions. One of the major limiting factors in gene therapy has been the development of safe and effective delivery systems.

The emphasis of our most recent research efforts is on imaging guided drug delivery. The recent emergence of "molecular imaging" has set the stage for an evolutionary jump in diagnostic imaging and therapy. The ability to incorporate drugs or genes into detectable site-targeted nanosystems represents a new paradigm in therapeutics that will usher in an era of image-based drug delivery.

We have developed a novel gene therapy system based on the use of commercially available ultrasound contrast agents and adenoviruses that enhance the specificity of gene transfer in vitro as well in vivo. Ultrasound-mediated microbubble destruction improves the efficacy and reduces the non-specific expression of gene therapy vectors providing a useful tool for manipulating gene expression in the living animal. We are currently working on further developing this useful targeting gene therapy tool to help closing the gap that still exist between laboratory bench and bedside application.

Most recent publications

Giacinti L., Claudio P.P., Giordano A. Epigenetic Information and Estrogen Receptor Alfa Expression in Breast Cancer. The Oncologist, 2006 Jan;11(1):1-8.

Merola E. Claudio PP, Giordano A. p53 and the malignant progression of Barrett's esophagus. J Cell Physiol. Mar; 206 (3):574-7, 2006.

Francesca Sanseverino, Rosa Santopietro, Michela Torricelli, Giuseppina D’Andrilli, Gabriele Cevenini, Alessandro Bovicelli, Lorenzo Leoncini, Giovanni Scambia, Felice Petraglia, Antonio Giordano and Pier Paolo ClaudiopRb2/p130 and VEGF expressions in endometrial carcinoma in relation to angiogenesis and tumor histopathologic grade. Cancer Biol Ther. 2006 Jan 22;5(1).

Elettra Merola, Eliseo Mattioli, Corrado Minimo, Weineng Zuo, Carla Rabitti, Michele Cicala, Renato Caviglia, Lucio Pollice, Antonio Giordano and Pier Paolo Claudio. Immunohistochemical evaluation of pRb2/p130, VEGF, EZH2, p53, p16, p21waf-1, p27, and PCNA in Barrett’s Esophagus. Journal Cell Physiology, 207(2): 512-9, 2006.

Vogiatzi, P, De Falco G., Claudio PP, Giordano A. How Does the Human RUNX3 Gene Induce Apoptosis in Gastric Cancer? Latest Data, Reflections and Reactions. Cancer Biol Ther. (4):371-374, 2006.

Abbadessa G., Santoro A., and Claudio P.P. Meeting Report: 42nd Annual Meeting of the American Society of Clinical Oncology (ASCO) June 2-6, 2006, Atlanta, GA. Drugs of the Future 31:(7), 2006.

Antonio Graziano, Vincenzo Desiderio, and Pier Paolo Claudio. Stem cells in tissue engineering for therapeutic use, a promising tool or an approachable reality? Drugs Future 31(12): 1117, 2006.

Pier Paolo Claudio, Chiara Mariano, Sujatha Radhakrishnan, Kamel Khalili, Mahmut Safak, Antonio Giordano, Shohreh Amini, and Bassel E Sawaya. Phosphorylation of p53 by cdk9 prevents HIV-1 gene transcription and viral replication. Journal Cell Physiology 208(3): 602-612, 2006.

Genovese C., Trani D., Caputi M., Claudio, P.P. Cell cycle control and beyond: emerging roles for the retinoblastoma gene family. Oncogene. 2006 Aug 28;25(38):5201-9.

Vogiatzi, P., Abbadessa, G., Cassone, M., Claudio, P.P. The limitless role of p53 in cell cycle machinery: good news or bad news? Cancer Biol Ther. 2006 Sep; 5(9):1090-3.

Vattemi M, and Claudio PP. Adenoviral gene therapy in head and neck cancer. Drug News Perspect. 2006 Jul-Aug;19 (6):329-37.

Howard, C.M., Forsberg F., Liu, J.B., Merton D.A., Minimo C., Pier Paolo Claudio Ultrasound guided site specific gene delivery system using adenoviral vectors and commercial ultrasound contrast agents. Journal Cell Physiology 2006 Nov; 209 (2):413- 21.

Paraskevi Vogiatzi, Marco Cassone, and Pier Paolo Claudio. On the road to personalizing gene therapy in gastric cancer: proposals for transforming dreams into reality. Drug News Perspect. 2006 Nov;19(9):533-40.

Eliseo Mattioli, Paraskevi Vogiatzi, Ang Sun, Giovanni Abbadessa, Giulia Angeloni, Domenico D’Ugo, Daniela Trani, John P. Gaughan, Fabio Maria Vecchio, Gabriele Cevenini, Roberto Persiani, Antonio Giordano, and Pier Paolo Claudio Immunohistochemical analysis of pRb2/p130, VEGF, EZH2, p53, p16 INK4A, p27KIP1, p21WAF1, Ki-67 expression patterns in gastric cancer. J Cell Physiol. 2007 Jan; 210(1):183-91.

Bagella, Tiziana Tonini, Giuliano Cottone, Pier Paolo Claudio, Marco G. Paggi, Antonio De Luca, Antonio Giordano. A small molecule based on the pRb2/p130 spacer domain leads to inhibition of cdk2 activity and cell cycle arrest. Oncogene, 2007 Mar 22;26(13):1829-39.

De Falco, G., Leucci, E., Lenze, D., Piccaluga, PP, Claudio, PP, Onnis, A., Cerino, G., Nyagol, J., Mwanda, W., Bellan, C., Hummel, M., Pileri, S., Tosi, P., Stein, H., Giordano, A., Leoncini, L. Gene-expression analysis identifies novel RBL2/p130 target genes in endemic Burkitt's lymphoma cell lines and primary tumors. Blood. 2007 Aug 15;110(4):1301-7.

Giovanni Abbadessa, Paraskevi Vogiatzi, Lorenza Rimassa and Pier Paolo Claudio. Antiangiogenic drugs currently used for colorectal cancer: what other pathways can we target to prolong responses? Drug News and Perspectives, June 2007, 20 (5), 1-7.

Candace M. Howard and Pier Paolo Claudio Meeting report of the 2006 Radiological Society of North America (RSNA). Molecular imaging: Novel techniques that not only visualize cellular changes driving disease processes before they become apparent anatomically, but also useful therapeutic tools for multiple diseases? Drugs of the Future, 2007.

Emanuela Vattemi and Pier Paolo Claudio Advances and Perspectives of Gene- Based therapy for Brest Cancer. Drugs Fut 32(6): 507, 2007.

Emanuela Vattemi and Pier Paolo Claudio Tumor Suppressor Genes as Cancer Therapeutics Drugs News Perspectives Oct;20 (8):511-20, 2007.

Paraskevi Vogiatzi, Pierpaolo Aimola, Scarano M. Irene and Pier Paolo Claudio. Epigenome: from the control of cell growth to cancer. Drug News Perspectives Dec;20(10):627-33, 2007.

Caracciolo V, Reiss K, Crozier-Fitzgerald C, De Pascali F, Macaluso M, Khalili K, et al. Interplay between the retinoblastoma related pRb2/p130 and E2F-4 and -5 in relation to JCV-TAg. J Cell Physiol 2007 Jul; 212 (1): 96-104.

Gilberto Sammartino, Gaetano Marenzi, Candace Howard, Oreste Trosino, Corrado Minimo, Luigi Califano, and Pier Paolo Claudio. Chondrosarcoma of the jaw: an anterior mandibular localization. A case report with a four-year S. E. Kelly, Di Benedetto A., Valluri, J.V., Claudio, P.P. Selection and Proliferation of Stem Cells. Gravitational and Space Biology, 2008.

Manuela Vattemi and Pier Paolo Claudio. The feasibility of Gene Therapy in the Treatment of Head and Neck Cancer. Head and Neck Oncology. Invited Review Article. Head Neck Oncol. 2009 Jan 12;1(1):3.

Manuela Vattemi and Pier Paolo Claudio. CONTUSUGENE LADENOVEC. Monograph, Drugs of the Future 2009, 34(3):1-6.

Adelaide Greco, Altomare DiBenedetto, Candace Howard, Sarah Kelly, Yulia Dementieva, Michele Miranda, Arturo Brunetti, Marco Salvatore, Luigi Claudio, Devanand Sarkar, Paul B. Fisher, and Pier Paolo Claudio. Eradication of therapy-resistant human prostate tumors using an ultrasound guided site-specific Mda7/IL-24 cancer terminator virus. Mol Ther 2010 Feb; 18 (2): 295-306.

Sammartino G, Tia M, Gentile E, Marenzi G, Claudio PP. Platelet-rich plasma and resorbable membrane for prevention of periodontal defects after deeply impacted lower third molar extraction. J Oral Maxillofac Surg 2009 Nov; 67 (11) : 2369-2373.

Vogiatzi P, Cassone M, Claudio L, Claudio PP. Targeted therapy for advanced prostate cancer: Looking through new lenses. Drug News Perspect 2009 Dec; 22 (10): 593-601.

Aimola P, Desiderio V, Graziano A, Claudio PP. Stem cells in cancer therapy: From their role in pathogenesis to their use as therapeutic agents. Drug News Perspect 2010 Apr; 23 (3): 175-183.

Francesco Papa, Claudio Banzi, Maria Cristina Maltarello, Elio D’Agostino, Pierpaolo Aimola, Mauro Farella, Antonio Cortese, Raffaele Sagliocco and Pier Paolo Claudio. Outcome of 47 consecutive sinus lift operations using aragonitic calcium carbonate associated with autologous platelet-rich plasma: clinical, histologic, and histomorphometrical evaluations. J Craniofac Surg 2009 Nov; 20 (6): 2067-2074.

Cortese A, Savastano M, Savastano G, Papa F, Howard CM, Claudio PP. Maxillary Constriction Treated by a New Palatal Distractor Device: Surgical and Occlusal Evaluations of 10 Patients. J Craniofac Surg 2010 Feb 24.

Kelly SE, Di Benedetto A, Greco A, Howard CM, Sollars VE, Primerano DA, et al. Rapid selection and proliferation of CD133+ cells from cancer cell lines: chemotherapeutic implications. PLoS One 2010; 5 (4): e10035.

For a list of publications prior to 2006, click here.


Fluorescence imaging of mice tissues and DB-1melanoma xenografts obtained from mice injected in their tail vein with complement treated Ad-GFP/microbbubbles demonstrating site-specific delivery of the transgene. A: Nude mice with melanoma xenografts (DB-1 cells) implanted on its flank; (B) dissected tumor showing the vascular axis; (C) US enhancement of tumor vasculature by US- targeted microbubble destruction (see red arrowhead). D–F: H&E staining of tumor, hearth, and lung, respectively; (G–I) lightmicroscopy of tumor, hearth, and lung, respectively; (J–L) fluorescence microscopy of tumor, hearth, and lung, respectively.

Tumor growth inhibition of human lung carcinoma cells in nude mice and the average tumor volume over time of two separate studies. At day 15, tumors were transduced with an intratumoral injection (20 ml) of a solution containing 5 x 106 retroviruses carrying the puromycin resistance gene alone (a and b), the lacZ gene (c and d), or the p130 gene (e and f).

2010 Laboratory personnel

Dr. Claudio's 2010 Lab Personnel

Front Row to Back Row:

Oksana Bailiff, Allison M. Wolf, IIaira Naldi, Flavia De Carlo, Sarah Don-Mathis, Dr. Pier Paolo Claudio
Andy Wendt, Colleen Conlon, Miranda Carper, Rounak Nande