Pier Paolo Claudio, M.D., Ph.D.

Pier Paolo Claudio, M.D., Ph.D.Associate Professor
Department: Biochemistry and Microbiology
Research Cluster: Cancer Biology
Office and Laboratory: McKown Translational Genomic Research Institute (TGRI) 1600 Medical Center Drive, Huntington, WV
Phone: (304) 696-3516 | E-mail: claudiop@marshall.edu

Research Interests

The focus of our laboratory is to understand the molecular mechanisms governing malignant transformation and to translate from the bench to the bedside tailored novel therapeutic strategies.

Translational research (applied research aimed at closing the gap between the laboratory and the bedside) is the main focus of our studies.

In our laboratory, that is located within the Translational Genomic Research Institute at the Edwards Cancer Center, we have been focusing on the effects that chemotherapy drugs and various diet components have on the growth and survival of the root of cancer, i.e. the cancer stem-like cells (CSLCs).

We have developed a cell culture method that enables the selection and proliferation of CSLCs from the bulk of tumor cells of patient tumor biopsies. Using this cell culture method we have established a laboratory-developed chemosensitivity test, the ChemoID® assay (Figure 1), which compares the sensitivity of CSLCs vs. bulk of tumor cells to chemotherapy. We are using this method to predict tailored chemotherapy strategies for lung, brain/spine, and breast cancer tumors in phase-I clinical trials.

ChemoID Assay Rationale_Fig1

Figure 1. Our strategy is to improve cancer treatment by specifically targeting cells that are thought to be critical to the activity and survival of cancer and that are known as cancer stem cells.

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 20 years studies to understand the crosstalk between those factors that contribute to cancer progression versus those that protect from it and to use them to our advantage to defeat cancer.

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.

Another emphasis of our research efforts is on imaging-guided drug delivery. Our ability to incorporate drugs or genes into detectable site-targeted nanosystems represents a new paradigm in 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 (Figure 2). We are currently working on further developing this useful targeting gene therapy tool to help close the gap that still exist between laboratory gene therapy studies and their bedside applications.

Firefly Luciferase Gene Transfer_Fig2

Figure 2. Detection of microbubble-assisted Firefly Luciferase gene transfer through whole animal imaging. Panel a) is the ultrasound image of a tumor xenograft. Panel b) is the image from a mouse that received ultrasound on the tumor implanted in the left flank showing specific luciferase luminescent signal at 24 hours from the treatment. Panel c) is the image from the same mouse as in panel b showing specific luminescent signal at 1 week from the treatment.

Selected Publications

Antonio Cortese, Germano Savastano, Massimo Amato, Antonio Cantone, Ciro Boschetti, and Pier Paolo Claudio. New palatal distraction device by both bone borne and tooth borne force application in a paramedian bone anchorage site: surgical and occlusal considerations on clinical cases. J Craniofac Surg. 2014 Mar;25(2):589-95. doi: 10.1097/SCS.0000000000000674. PMID: 24577304

Wolf MA, Claudio PP. Benzyl Isothiocyanate Inhibits HNSCC Cell Migration and Invasion, and Sensitizes HNSCC Cells to Cisplatin. Nutr Cancer. 2014 Jan 21. [Epub ahead of print] PMID: 24447182

Asen Begashev, Shongshan Fan, Ruma Mukerjee, Pier Paolo Claudio, Tinatin Chabrashvili, Roger Leng, Samuel Benchimol, Bassel E Sawaya. Cdk9 phosphorylates Pirh2 protein and prevents degradation of p53 protein. Cell Cycle. 2013 May 15;12(10):1569-77. doi: 10.4161/cc.24733. Epub 2013 Apr 19. PMID: 23603988

Antonio Cortese, Mauro Savastano, Antonio Cantone, and Pier Paolo Claudio. A new palatal distractor device for bodily movement of maxillary bones by rigid self-locking mini plates and screws system. J Craniofac Surg. 2013 Jul;24(4):1341-6. doi: 10.1097/SCS.0b013e31828041a7. PMID: 23851803

Flavia De Carlo, Theodore R Witte, W Elaine Hardman, Pier Paolo Claudio. Omega-3 eicosapentaenoic acid decreases CD133 colon cancer stem-like cell marker expression while increasing sensitivity to chemotherapy. PLoS One. 2013 Jul 16;8(7):e69760. doi: 10.1371/journal.pone.0069760. Print 2013. PMID: 23874993

Rounak Nande, Adelaide Greco, Michael S. Gossman, Jeffrey P. Lopez, Luigi Claudio, Marco Salvatore, Arturo Brunetti, James Denvir, Candace M. Howard, and Pier Paolo Claudio. Microbubble-assisted p53, RB, and p130 gene transfer in combination with radiation therapy in prostate cancer. Current Gene Therapy, 2013 Jun 1;13(3):163-74. PMID: 23531191

Rounak Nande, Altomare Di Benedetto, Pierpaolo Aimola, Flavia De Carlo, Miranda Carper, Charlene D. Claudio, James Denvir, Jagan Valluri, Gary C. Duncan, and Pier Paolo Claudio. Gene transfer in a spontaneous feline fibrosarcoma cell line. PLoS One. 2012;7(5):e37743. doi: 10.1371/journal.pone.0037743. Epub 2012 May 30. PMID: 22666387

Pierpaolo Aimola, Mara Di Benedetto, Marco Carmignani, Anna Rita Volpe, Luigi Claudio, Erik J. Tokar, Adrie van Bokhoven, Michael P. Waalkes, and Pier Paolo Claudio. Cadmium induces p53-dependent apoptosis in human prostate epithelial cell lines. PLoS ONE 7(3): e33647. doi:10.1371/journal.pone.0033647, 2012

Greco A, Mancini M, Gargiulo S, Gramanzini M, Claudio PP, Brunetti A, Salvatore M. Ultrasound biomicroscopy in small animal research: applications in molecular and preclinical imaging.   J Biomed Biotechnol. 2012;2012:519238. doi: 10.1155/2012/519238. Epub 2011 Oct 25. Review. PMID: 22163379

Monia Taranta, Ilaria Naldi, Settimio Grimaldi, Laura Salvini, Pier Paolo Claudio, Francesca Rocchio, Alex F. Munoz, Stefano Prete, Caterina Cinti. Magnetically driven bioreactors as new tools in drug delivery. Journal Bioanalytical and Biomedicine, 2011, S5.

Cortese A, Savastano M, Savastano G, Claudio PP. One-step transversal palatal distraction and maxillary repositioning: technical considerations, advantages, and long-term stability. J Craniofac Surg. 2011 Sep;22(5):1714-9.

Differentiation of Dental Stem Cells in Simulated Microgravity. C. Conlon, Valluri, V.S., Valluri, J.V., Claudio, Pier Paolo. Gravitational and Space Biology Volume 25 (1) Sept 2011.

Dash R, Azab B, Shen XN, Sokhi UK, Sarkar S, Su ZZ, Wang XY, Claudio PP, Dent P, Dmitriev IP, Curiel DT, Grant S, Sarkar D, Fisher PB. Developing an effective gene therapy for prostate cancer: New technologies with potential to translate from the laboratory into the clinic. Discov Med. 2011 Jan;11(56):46-56.

Michael S. Gossman, Indra J. Das, Subhash C. Sharma, Candace M. Howard, Jeffrey P. Lopez, and Pier Paolo Claudio. Mouse tumor dose assessment from megavoltage x-ray radiation using various detectors with simulation comparisons. Health Physics Journal, 2011, 101(6):746-753.

Ruma Mukerjee, Pier Paolo Claudio, J. Robert Chang, Luis Del Valle, and Bassel E Sawaya. Transcriptional regulation of HIV-1 gene expression by p53. Cell Cycle, 2010 Nov 15;9(22):4569-78. Epub 2010 Nov 15.

Vogiatzi P, Claudio PP. Efficacy of abiraterone acetate in post-docetaxel castration-resistant prostate cancer. Expert Rev Anticancer Ther. 2010 Jul;10(7):1027-30.

Pedersini R, Vattemi E, Claudio PP. Adenoviral gene therapy in high-grade malignant glioma. Drug News Perspect. 2010 Jul-Aug;23(6):368-79.

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.

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.

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.

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

Book Chapters

Rounak Nande and Pier Paolo Claudio. (2014)Ultrasound Contrast Agents in Cancer Therapy. In P.P. Claudio & V. Vogiatzi (Eds.),Cutting edge therapies for cancer in the 21st century. Oak Park, IL: Bentham Science Publishers Ltd.

Wolf, M.A. and P.P. Claudio (2012). Isothiocyanates target carcinogenesis during tumor initiation, promotion, and progression/Article. In P.P. Claudio & R.M. Niles (Eds.), Nutrition and Cancer: From Epidemiology to Biology (p79-86). Oak Park, IL: Bentham Science Publishers Ltd.

Paraskevi Vogiatzi, Maria Irene Scarano, and Pier Paolo Claudio. Chapter 14. Epigenetic Targets and Drug Development. In Cancer Epigenetics: Biomolecular Therapeutics in Human Cancer. John Wiley and Sons Ltd, March 2012, Pages: 436.

Claudio P.P. and Vogiatzi P. (2010): Distinct roles of the pocket proteins in the control of cell cycle. In: Signal Transduction: Pathways, Mechanisms and Diseases. Springer Ed. 353-374.

Claudio P.P. and Denning D. (2007): Nasopharyngeal carcinoma. In Cancer Research, an encyclopedic reference book. Springer Ed. 615-618.

Books

Claudio P.P., Vogiatzi, V., Editors. “Cutting edge therapies for cancer in the 21st century”.   Bentham, 2014

Claudio, P.P., Niles, R.M., Editors. “Nutrition and Cancer, from Epidemiology to Biology”. Bentham, August 2012

Laboratory Personnel

Pier Paolo Claudio, M.D., Ph.D.

Walter Neto, M.D.

Miranda Carper – Ph.D. candidate

Sarah Mathis – Ph.D. student

Rounak Nande – Ph.D. student

Benji Pyles, Biological Sciences, M.S. student

Logan Lawrence – Biological Sciences, M.S. student

Danielle R. McCallister – VMD student