Pier Paolo Claudio

Biography

As a research fellow at Temple University (1993-1994), I studied the involvement of the retinoblastoma-related protein RBL2 in the regulation of cell cycle and observed for the first time that the retinoblastoma-related protein RBL2 can selectively suppress the growth of certain cancer cell lines which are resistant to the growth suppressive effects of both RB/p105 and RBL1 (p107), dissecting distinct properties of the retinoblastoma family of proteins. During my tenure at Temple University, I have also cloned two important kinases, PITALRE (cdk9) and PISSLRE (cdk10). Cdk9 has been later identified as one of the major key players regulating Pol-II-mediated RNA elongation and HIV replication.
As a postdoctoral fellow at Jefferson University (1994-1996), I carried out studies involving the role of the retinoblastoma protein (RBL2) in gene therapy animal studies. In studies published in the Journal of the National Cancer Institute and in the Cancer Research Journal, I have collaborated toward addressing or directly tackled the question of whether the forced overexpression of the RBL2 gene can suppress in vivo the growth of virally transformed tumor cell lines with the use of a novel animal model system. Our findings served to highlight the unanswered questions of how the RBL1 and RBL2 genes relate to the RB tumor suppressor pathway and whether they are, in fact, bona fide tumor suppressor genes. This data earned an editorial article in the Journal of the National Cancer Institute.
As a faculty at Jefferson University (1996-2002), I have further demonstrated the growth-suppressive properties of RBL2 in various cancer cell lines as well as in vivo in xenograft mouse lung cancer and glioblastoma models using viral delivery of the RBL2 gene, suggesting that RBL2 could be a novel biological drug. In a follow-up of these in vivo studies, I observed that overexpression of the wild-type RBL2 gene interferes with the angiogenic process by specific down-regulation of the VEGF gene product. During my tenure at Jefferson University, I have also investigated the role of adenoviral gene therapy in the prevention of restenosis after angioplasty using a viral vector to overexpress the RBL2 gene. This method to inhibit restenosis using an Adenoviral vector to transfer RBL2 was awarded a US patent in 2003.
Since then the focus of my laboratory has been to understand the molecular mechanisms governing malignant transformation in order to tailor novel therapeutic strategies. Toward this end, I 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.
As a faculty at Temple University (2002-2006), I expanded my research to develop a novel delivery system for safer gene therapy protocols that employed the unique characteristics of ultrasound contrast agents to deliver therapeutic genes to diseased tissue. 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 ability to incorporate drugs or genes into detectable site-targeted nanosystems represented a new paradigm in therapeutics that my laboratory has been exploring as a therapeutic alternative and that we hope will usher in an era of image-based drug delivery.
As a faculty at Marshall University (2006-2015), I have implemented in the past 10 years the ultrasound-guided gene therapy system initially developed at Temple University, and which has been funded by two NIH grants during my tenure at Marshall University. The goal of the research performed in my laboratory at Marshall University has been to explore ultrasound contrast agents (microbubble) mediated delivery of anti-cancer therapeutic using freeze-dried microbubbles to prostate and pancreatic cancers. Loading payload and reproducibility of a viral cancer therapeutic payload is being examined. Delivery of payload to tumors is being examined in a mouse model of prostate and in one of pancreatic cancer. We have shown that 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 working on developing this useful targeting gene therapy tool further to help close the gap between the laboratory bench and bedside applications for this therapeutic tool. Since at Marshal University, my laboratory has focused on understanding the molecular mechanisms governing malignant transformation and translating from the bench to the bedside tailored novel therapeutic strategies. In my laboratory, which was 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 cells (CSCs).
We have developed a cell culture method that enables the selection and proliferation of CSCs from the bulk of tumor cells of patient tumor biopsies. Three international patents cover the procedure. Using this cell culture method we have established a laboratory-developed chemosensitivity test, the ChemoID® assay, which compares the sensitivity of CSCs vs. bulk of tumor cells to chemotherapy. ChemoID® is a second-generation functional drug response assay, that uses a patient’s live tumor cells to indicate which chemotherapy agent (or "combinations") will kill not only the bulk of the tumor but also the cancer stem cells (CSCs) that are known to cause cancer to recur. As cancer stem cells form a very small portion of a tumor, the current treatments often fail to choose drugs that act on cancer stem cells, which are responsible for tumor recurrence. Targeting of CSCs alongside the bulk of other cancer cells is a new paradigm in cancer treatment. This constitutes an important advantage of the ChemoID® approach over other assays available. By testing multiple chemotherapies on a patient's tumor cells before clinically treating a cancer patient, ChemoID® Assay may enable faster reaction time to administer the optimum selection of chemotherapy drug(s), increased patient survival, and lower treatment costs by eliminating unnecessary chemotherapies, and decreased levels of toxicity.
ChemoID® drug response assay is currently a laboratory-developed test (LDT) that is performed in a CLIA/CAP accredited laboratory at Cabell Huntington Hospital/Edwards Comprehensive Cancer Center to help oncologists tailor chemotherapy for patients in an individualized manner.
As a faculty at the University of Mississippi (2015-present), I am continuing to translate into medical practice two of the patented technologies from my laboratory, the ChemoID® Drug Response Assay and the Ultrasound Guided Microbubble Gene Delivery System. The drug response platform we developed can also be used to screen the efficacy of several compounds on primary cell lines that we have generated from our clinical studies on a wide variety of cancers. We are currently screening for metabolically active compounds against cancer stem cells by evaluating natural products (botanical extracts or purified compounds) in order to develop new targeted therapies against the root of cancer and or improved chemotherapy protocols for cancer patients. The focus of my laboratory is to bridge and integrate the basic cancer research conducted at both the NCNPR/School of Pharmacy and the University of Mississippi School of Medicine and Cancer Institute in Jackson with the various clinical oncology research groups, oncology surgeons, radiation oncologists, and radiologists in an effort to translate discoveries and laboratory work conducted at OleMiss and UMMC into clinical evaluation and precision medicine.

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